PD184352 (CI-1040)

PD184352 (CI-1040) is an ATP non-competitive MEK1/2 inhibitor with IC50 of 17 nM in cell-based assays, 100-fold more selective for MEK1/2 than MEK5. Phase 2.

Price Stock Quantity  
USD 140 In stock
USD 70 In stock
USD 120 In stock
USD 270 In stock
USD 670 In stock
USD 770 In stock
Bulk Inquiry

Massive Discount Available

Free Overnight Delivery on all orders over $ 500.

PD184352 (CI-1040) Chemical Structure

PD184352 (CI-1040) Chemical Structure
Molecular Weight: 478.67

Validation & Quality Control

Product Use Citation(41)

Customer Product Validation(12)

Quality Control & MSDS

Related Compound Libraries

PD184352 (CI-1040) is available in the following compound libraries:

MEK Inhibitors with Unique Features

Product Information

  • Compare MEK Inhibitors
    Compare MEK Products
  • Research Area
  • Combination Therapy
    Combination Therapy

Product Description

Biological Activity

Description PD184352 (CI-1040) is an ATP non-competitive MEK1/2 inhibitor with IC50 of 17 nM in cell-based assays, 100-fold more selective for MEK1/2 than MEK5. Phase 2.
Targets MEK1 [1]
(Cell-free assay)
MEK2 [1]
(Cell-free assay)
IC50 17 nM 17 nM
In vitro CI-1040 treatment produces a reduction of pMAPK levels in multiple tumor cells including Colon 26, BX-PC3 pancreatic, A431 cervical, HT-29 colon, ZR-25-1 breast and SKOV-3 ovarian carcinomas. CI-1040 treatment doesn't inhibit the phosphorylation of Jun kinase, p38 kinase or Akt, indicating CI-1040 specifically targets MEK. Inhibition of MAPK activation by CI-1040 prevents cell cycle progression and induces a G1 block. [1] The IC50 for inhibition of MEK1 by CI-1040 is 0.3 μM, 15-fold higher than the concentration required to inhibit the EGF-induced activation of ERK2 in Swiss 3T3 cells. These results indicate CI-1040 exerts its effects on cells by suppressing the activation of MKK1, and not by blocking its activity. 2 nM PD184352 inhibits the activation of MKK1 in Swiss 3T3 cells by 50%, while over 100-fold concentration of CI-1040 inhibits MEK1 in vitro. PD184352 also inhibits the Raf-catalysed phosphorylation of MEK1 without any effect on the Raf-catalysed phosphorylation of myelin basic protein. [2] CI-1040 inhibits 86% of papillary thyroid carcinoma (PTC) cell growth with the RET/PTC1 rearrangement at 10μM compared with cells treated with DMSO only. CI-1040 shows potent inhibition to PTC cells (BRAF mutation) with GI50 of 52 nM, but low activity to RET/PTC1 rearrangement type with GI50 of 1.1 μM. [3] A recent research indicates CI-1040 increases the apoptotic effect of BMS-214662 in a CML blast crisis cell line, K562, and in primary chronic phase CD34+ CML cells. [4]
Cell Data
Cell LinesAssay TypeConcentrationIncubation TimeFormulationActivity DescriptionPMID
H9NULX[HJrT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MkHsTWM2OD1yLkCyNlc3KM7:TR?=Mki3V2FPT0WU
CHP-212MYHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MUPJR|UxRTBwMEK4PFUh|ryPM3nkR3NCVkeHUh?=
EoL-1-cellNY\MdWh5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=Mk\DTWM2OD1yLkC0NVUzKM7:TR?=M2\lcnNCVkeHUh?=
DU-4475MY\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NFzWPFhKSzVyPUCuNFc2QTlizszNNX;NU|M{W0GQR1XS
MMAC-SFM3W5R2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7MojoTWM2OD1yLkGwPVc1KM7:TR?=NWDVOWVHW0GQR1XS
AGSM3K3c2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7M335PGlEPTB;MD6xNVcyOyEQvF2=NVTsPFdQW0GQR1XS
M14MlGzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?M4O3NWlEPTB;MD6xOVQ3QCEQvF2=M{DDXnNCVkeHUh?=
CP50-MEL-BMWPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MkHVTWM2OD1yLkG3NlU1KM7:TR?=NXXHOJZnW0GQR1XS
C32M2nwPWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NYfpbIpbUUN3ME2wMlE6ODd{IN88US=>MlLSV2FPT0WU
KMOE-2MnjGS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?M4fvTWlEPTB;MD6xPVc6PSEQvF2=MYrTRW5ITVJ?
A101DNVq4WGVCT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NGjzOI5KSzVyPUCuNlE1KM7:TR?=M2[0bnNCVkeHUh?=
KM12MVXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MnzaTWM2OD1yLkK0NFU4KM7:TR?=MYfTRW5ITVJ?
HSC-4MVvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NWfHfI5SUUN3ME2wMlI1Ozl3IN88US=>NX3wb4h2W0GQR1XS
NOMO-1MXXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NUi1SVZCUUN3ME2wMlI2PzR{IN88US=>NU\P[GV5W0GQR1XS
MZ7-melMWnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NHW1dYFKSzVyPUCuNlY{PCEQvF2=NHXpTWVUSU6JRWK=
ACNNWr4Vmk2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MnjpTWM2OD1yLkK2O|M4KM7:TR?=NXnsbGxpW0GQR1XS
MEL-HONUTDdpA6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NITabFFKSzVyPUCuNlc3PTJizszNNUW3OWdYW0GQR1XS
BHT-101NXzzU3RiT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NViwdZJNUUN3ME2wMlI5PjB4IN88US=>NF\YVYtUSU6JRWK=
SK-MEL-28NV7MO41nT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NFPhdZpKSzVyPUCuN|A1ODlizszNMmTjV2FPT0WU
KG-1NFm2bXRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MYjJR|UxRTBwM{C2Olgh|ryPMlKyV2FPT0WU
COLO-679MYDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NFfRR3dKSzVyPUCuN|I4OiEQvF2=MXzTRW5ITVJ?
SK-MEL-24MnP3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NHnk[5lKSzVyPUCuN|I5OTNizszNM4KzOXNCVkeHUh?=
G-361MYnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MkT2TWM2OD1yLkO2O|k2KM7:TR?=NUWzeJZJW0GQR1XS
KY821MX7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?M1TrNGlEPTB;MD6zO|kyKM7:TR?=MlzkV2FPT0WU
KASUMI-1MnLuS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NVTFPIVzUUN3ME2wMlM6QSEQvF2=NE\VZldUSU6JRWK=
HL-60NVnY[msxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MVLJR|UxRTBwNEGxNFch|ryPMXnTRW5ITVJ?
K5MljPS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NH\zZXBKSzVyPUCuOFMyOTdizszNNYTlZno5W0GQR1XS
KU812NXHiUWFZT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NUnpe|F6UUN3ME2wMlQ2Ojl7IN88US=>Mk\iV2FPT0WU
SH-4MYnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MVjJR|UxRTBwNE[yOVYh|ryPMmDHV2FPT0WU
HTC-C3MlKwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?M3LCOGlEPTB;MD60OlU{OSEQvF2=M1O5N3NCVkeHUh?=
CP66-MELMVrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?M{jlWWlEPTB;MD60PFgxQSEQvF2=NWHUNYFxW0GQR1XS
WM-115MnzWS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NEHIc3BKSzVyPUCuOFkzPTdizszNMW\TRW5ITVJ?
A2780Mon1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NET5WW5KSzVyPUCuOFk5OjNizszNNVfleGJTW0GQR1XS
P12-ICHIKAWAMmLJS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NYL6RVR7UUN3ME2wMlYyOjJzIN88US=>NG\5WnFUSU6JRWK=
HMV-IINH\UTodIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MkjzTWM2OD1yLk[0OFY2KM7:TR?=NX7YcIUzW0GQR1XS
HT-144NIP6O4tIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=M1nQNWlEPTB;MD62OFY2PyEQvF2=NGXNWopUSU6JRWK=
LB2518-MELM13TbGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7M3LOfGlEPTB;MD63NVY{OiEQvF2=MWrTRW5ITVJ?
NCI-SNU-1MVzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MlS2TWM2OD1yLke1OFM{KM7:TR?=NULI[W9kW0GQR1XS
C2BBe1M{Lqc2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7NHHwW|NKSzVyPUCuPFExOjNizszNNF3WdndUSU6JRWK=
PSN1NVvq[Jk5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NYm2e2JyUUN3ME2wMlk3OTl4IN88US=>MUPTRW5ITVJ?
UACC-257M{LwUGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NFjOU4NKSzVyPUCuPVY1PzNizszNMn6xV2FPT0WU
RVH-421NVr0[VNWT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MlTpTWM2OD1yLkm3NVgh|ryPNXPhNY1bW0GQR1XS
GP5dM3LBXWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NE\heWdKSzVyPUCuPVg{ODhizszNM4PPR3NCVkeHUh?=
TYK-nuNHjnWGRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NYiy[2Y6UUN3ME2xMlA{OTd{IN88US=>NF3ZV4pUSU6JRWK=
SK-N-ASNHSyV4RIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NWLXUYVDUUN3ME2xMlA4QTR5IN88US=>NFrYZlFUSU6JRWK=
SW620NXnNRVU1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NW\SfpE1UUN3ME2xMlE{PTN2IN88US=>MVTTRW5ITVJ?
HuP-T4MkDFS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MX\JR|UxRTFwMUizOVkh|ryPMXzTRW5ITVJ?
A549MV3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MVrJR|UxRTFwMUm1O|Yh|ryPMXnTRW5ITVJ?
MewoMlv5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MWfJR|UxRTFwMkCyO|Yh|ryPMWrTRW5ITVJ?
ONS-76NW\CWHVRT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NUe4cnh2UUN3ME2xMlIzODR7IN88US=>Mk\5V2FPT0WU
SK-MEL-1MULHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?M2S0NmlEPTB;MT6yN|QyQSEQvF2=MV\TRW5ITVJ?
RCM-1NGH0NoVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MYrJR|UxRTFwMkSwOFch|ryPNEj0N2lUSU6JRWK=
H-EMC-SSM3XKPGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7M3jpOWlEPTB;MT6yPVYxQCEQvF2=MX7TRW5ITVJ?
NCI-H2291MlnwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MVfJR|UxRTFwM{K1N|Yh|ryPMVvTRW5ITVJ?
SW1463NF;0W4NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NY\EOIVtUUN3ME2xMlM{PzJzIN88US=>MlWzV2FPT0WU
LS-411NNHjrUZdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MmDvTWM2OD1zLkSwOVE4KM7:TR?=MkjHV2FPT0WU
BV-173NV\HS|k1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MX3JR|UxRTFwNESwNVUh|ryPNIrSSWJUSU6JRWK=
LS-513Mnz0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MnexTWM2OD1zLkS1NVkzKM7:TR?=NXfvU3F6W0GQR1XS
LoVoNUPOd|R[T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MmXKTWM2OD1zLkS2N|k6KM7:TR?=MVjTRW5ITVJ?
HO-1-N-1NIS5dHpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=M1XlXGlEPTB;MT61NVY{PCEQvF2=MYHTRW5ITVJ?
ML-2MUfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?M4L2NmlEPTB;MT61Nlg3QCEQvF2=NHXTT49USU6JRWK=
NCI-H1437M2\wbmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NUDTUIwxUUN3ME2xMlU2Ojd3IN88US=>M3PiXHNCVkeHUh?=
SW1116NX3sNos6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NXfqUnB3UUN3ME2xMlU3Ozl6IN88US=>NYq4RlczW0GQR1XS
A4-FukNF;QcYxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=M3PUdmlEPTB;MT61O|A1PSEQvF2=MkL5V2FPT0WU
HD-MY-ZM17te2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7MULJR|UxRTFwNUezO|Yh|ryPMXrTRW5ITVJ?
SK-MEL-2NGHzTndIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MkH3TWM2OD1zLkW3OFU6KM7:TR?=MnToV2FPT0WU
RT-112M{ftT2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7NFfEcJpKSzVyPUGuOVg6PTJizszNNHHGcnZUSU6JRWK=
COLO-829M3HVZWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NWS2TodEUUN3ME2xMlYzOjN{IN88US=>NETqVpZUSU6JRWK=
OVCAR-5NX3BfWljT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MoroTWM2OD1zLke3Olg4KM7:TR?=M17lNHNCVkeHUh?=
NB69NUXUWZIzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=M4jocWlEPTB;MT63PFQ3QSEQvF2=MYPTRW5ITVJ?
NCI-H292Mn3IS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NWHBdZJ1UUN3ME2xMlg3Pjl7IN88US=>MY\TRW5ITVJ?
LOXIMVIM1LTUWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NH;XRlNKSzVyPUGuPFk1OjdizszNMk\JV2FPT0WU
BPH-1NHeyRppIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NV3aPI5FUUN3ME2xMlg6PTlzIN88US=>NFywNVlUSU6JRWK=
A375NY\5XYxZT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=M2LUU2lEPTB;MT64PVcyPCEQvF2=M1Ttb3NCVkeHUh?=
LCLC-97TM1MX7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?M1O2RWlEPTB;MT65NlI2PiEQvF2=NYPWOld{W0GQR1XS
RXF393M2DG[Gdzd3e2aDDJcohq[mm2aX;uJGF{e2G7Ml7pTWM2OD1zLkm3PFg4KM7:TR?=MmLDV2FPT0WU
HCC70NV\sc29PT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NWDORnBMUUN3ME2yMlAzPDJ4IN88US=>NHPE[GVUSU6JRWK=
EM-2M4\xSmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NED4THJKSzVyPUKuNFcyQThizszNMV\TRW5ITVJ?
MZ2-MELNFy3TVlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NVrydHQyUUN3ME2yMlEyOTJ5IN88US=>MWPTRW5ITVJ?
HNNX;KdWRjT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MXnJR|UxRTJwMU[yO|gh|ryPMXnTRW5ITVJ?
A2058M3y2WWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NVT2NpRMUUN3ME2yMlE6Ojd7IN88US=>M1XGRnNCVkeHUh?=
NB7MWTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MYrJR|UxRTJwM{SwPFYh|ryPMUDTRW5ITVJ?
DOKMkDuS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MU\JR|UxRTJwM{W3O|Mh|ryPMWXTRW5ITVJ?
CAL-27NYXvb4ZuT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MX7JR|UxRTJwM{myN|Yh|ryPNH3kNWRUSU6JRWK=
BB65-RCCM4rSXGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MXnJR|UxRTJwNEC2O|Qh|ryPNIjneZZUSU6JRWK=
RDNHjidXNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NEPnOotKSzVyPUKuOFQ4OjNizszNM3m0T3NCVkeHUh?=
KNS-62M{nCdmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MXzJR|UxRTJwNUGxOlQh|ryPMUTTRW5ITVJ?
EW-13NUPafHVFT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MkLkTWM2OD1{LkW2N|M6KM7:TR?=MoLnV2FPT0WU
DBNV;OU|lQT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MlvXTWM2OD1{LkW4O|g5KM7:TR?=MVHTRW5ITVJ?
HCC2218NFnISopIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=M2fVOGlEPTB;Mj62OFc4QCEQvF2=NWPoPZdWW0GQR1XS
L-363NXfRSoNkT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NHLlNFNKSzVyPUKuO|Q{PyEQvF2=MmHlV2FPT0WU
CHL-1MXzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?M3G0UWlEPTB;Mj64NFc5PSEQvF2=NIL6Z2NUSU6JRWK=
BFTC-905M{X2emdzd3e2aDDJcohq[mm2aX;uJGF{e2G7M2Pi[GlEPTB;Mj64NlU{KM7:TR?=NI[2b2RUSU6JRWK=
HCE-TNIf0UnhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=M17Vd2lEPTB;Mj64N|I3PCEQvF2=NWjsdlFMW0GQR1XS
COLO-792M3W3Tmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NV[3S4h1UUN3ME2yMlg1ODJ5IN88US=>MmntV2FPT0WU
LB2241-RCCMXjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MoPwTWM2OD1{Lki1PFk{KM7:TR?=MofEV2FPT0WU
CAL-39M3Hafmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MUXJR|UxRTJwOEm5PVkh|ryPMYnTRW5ITVJ?
T-24MWLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NYXPW2l{UUN3ME2yMlkyOTF{IN88US=>NFu2WVRUSU6JRWK=
NCI-H727NIfie5ZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MojpTWM2OD1{LkmxO|k3KM7:TR?=M2PtcnNCVkeHUh?=
Ca9-22NFfCSotIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=M4jq[GlEPTB;Mj65O|I2PSEQvF2=MVvTRW5ITVJ?
MIA-PaCa-2NUfkVGNrT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MYfJR|UxRTNwMEC3PFEh|ryPMV7TRW5ITVJ?
HT-1080NYXyR5lxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MVLJR|UxRTNwMEG5PVch|ryPM1z2dHNCVkeHUh?=
D-423MGMmrPS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MVHJR|UxRTNwMEe3OVMh|ryPM3TB[HNCVkeHUh?=
LAMA-84NIfGPVRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MlrxTWM2OD1|LkGzOVgh|ryPMYLTRW5ITVJ?
SW780MU\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MnfRTWM2OD1|LkG0NlI6KM7:TR?=MoK0V2FPT0WU
KU-19-19MlzQS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?Ml;vTWM2OD1|LkG3NFM1KM7:TR?=MXLTRW5ITVJ?
COLO-741NXPjeVVjT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=M{\wSWlEPTB;Mz6xPFY4OyEQvF2=NFO4cW1USU6JRWK=
HSC-3MVfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MVnJR|UxRTNwMkOxOVEh|ryPNHOy[ItUSU6JRWK=
SN12CMoWwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?M4[1PWlEPTB;Mz6yOFcxOSEQvF2=NX\5bYZDW0GQR1XS
786-0NGfkTFdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MUDJR|UxRTNwMkeyOFMh|ryPNIrpdWNUSU6JRWK=
GAKNYPETmY5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MkLuTWM2OD1|LkOyOVYyKM7:TR?=MnrQV2FPT0WU
PANC-03-27NFzOZVhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NEeweJpKSzVyPUOuN|UxPDVizszNM4nVTXNCVkeHUh?=
CTB-1NXzqWZFKT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MVXJR|UxRTNwNEewOFch|ryPNI\MRmZUSU6JRWK=
A427M{\KOmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MXPJR|UxRTNwNUm1OVYh|ryPMmXQV2FPT0WU
EGI-1M{\0c2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7MnjXTWM2OD1|Lk[wOVg{KM7:TR?=NXfSTnBNW0GQR1XS
U-2-OSNXrjWFgxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=M1G4bGlEPTB;Mz62O|I2PiEQvF2=NHT4SW9USU6JRWK=
NCI-SNU-5M2XacWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7Mn\qTWM2OD1|Lk[3O|Mh|ryPMWLTRW5ITVJ?
SK-LU-1NYroXVMzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MmjWTWM2OD1|Lk[4O|k5KM7:TR?=Mnn4V2FPT0WU
697NE\4bVZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NHHzTXhKSzVyPUOuOlk3ODNizszNMYTTRW5ITVJ?
HPAF-IINFPMe5JIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NW\ST5VIUUN3ME2zMlc2PDlizszNNELncndUSU6JRWK=
NCI-H2087MWfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MXrJR|UxRTNwOES2O|Ih|ryPMXXTRW5ITVJ?
SK-MEL-3M2q5VWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NFLPTINKSzVyPUOuPFUyPTRizszNM3LVRXNCVkeHUh?=
CGTH-W-1MVTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?M2XFRWlEPTB;Mz64OVczPSEQvF2=NXS3NWN[W0GQR1XS
8505CNFjHNZlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NG\DcFdKSzVyPUOuPVAxPzhizszNMULTRW5ITVJ?
GAMGMlPGS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MVzJR|UxRTRwMEKzO|ch|ryPNXHZb5p4W0GQR1XS
SW626NXvu[IdQT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MXnJR|UxRTRwMES0PEDPxE1?NGfueIFUSU6JRWK=
CAL-62MYTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MofZTWM2OD12LkC3OFMh|ryPMYLTRW5ITVJ?
MHH-PREB-1M37RT2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7NXznW4FqUUN3ME20MlEzOTFzIN88US=>NHTHWINUSU6JRWK=
RPMI-7951NEPGOYxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NWPoT4Q3UUN3ME20MlI2PTh7IN88US=>MYjTRW5ITVJ?
HOP-92MYrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?M33oTWlEPTB;ND6yOVY4KM7:TR?=MX\TRW5ITVJ?
MDA-MB-231NE\hdpVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=Mo\BTWM2OD12LkK5NlI{KM7:TR?=M1LnbHNCVkeHUh?=
LAN-6NI\qSG5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NXTsUW12UUN3ME20MlMyPjN5IN88US=>MmXtV2FPT0WU
ALL-PONVvsZ2VrT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=M{\nO2lEPTB;ND6zOlE2PiEQvF2=M1KwXXNCVkeHUh?=
HHMXvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MXjJR|UxRTRwNEG1PVch|ryPMoH0V2FPT0WU
IGROV-1MnPJS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MYLJR|UxRTRwNEWxO|Eh|ryPNV;iSGZGW0GQR1XS
NCI-H358M4[xe2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7MoT4TWM2OD12LkS1N|g2KM7:TR?=MmiwV2FPT0WU
NB5NIXncG1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?=M4DVTWlEPTB;ND62NFM3QSEQvF2=M4jPN3NCVkeHUh?=
NCI-H747NH;RbGJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NXzkbZp[UUN3ME20MlY5QDB5IN88US=>M13Je3NCVkeHUh?=
NH-12NIe2VYFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NH24SpFKSzVyPUSuO|E3OjVizszNNUnY[WVMW0GQR1XS
LB1047-RCCM2rSZWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MWTJR|UxRTRwN{O4NVUh|ryPNUL3NGNlW0GQR1XS
EFO-27MUHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?M4jQRWlEPTB;ND63PFY3PyEQvF2=M1y1dnNCVkeHUh?=
EPLC-272HMWrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NWnYTHQ4UUN3ME20Mlk6PjZ7IN88US=>MmPtV2FPT0WU
CAL-54M3S4fGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7M3LufGlEPTB;NT6wNlY6PSEQvF2=Ml\nV2FPT0WU
H4MmjrS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NH\FenVKSzVyPUWuNFQzPTVizszNMYrTRW5ITVJ?
MOLT-13NEHne2tIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NILJOWxKSzVyPUWuNFY4PzZizszNNUfk[ZE4W0GQR1XS
CAL-33NW\JbmhZT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NHH0V4xKSzVyPUWuNVI{OTdizszNMVXTRW5ITVJ?
23132-87M2m3SGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NFvYPJVKSzVyPUWuNVY5PzJizszNMlXPV2FPT0WU
UM-UC-3NX:2dHFtT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NYPEXY44UUN3ME21MlE5ODR5IN88US=>Mn[yV2FPT0WU
HuH-7MkLkS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NUTmepdnUUN3ME21MlI4OTR5IN88US=>Mn[3V2FPT0WU
BCPAPMm\VS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?Mmi3TWM2OD13LkOyPVY6KM7:TR?=MmnMV2FPT0WU
AsPC-1NVPPTFdNT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MluyTWM2OD13LkO2O|Y{KM7:TR?=NF3rXZlUSU6JRWK=
NCI-H1155MWrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?M4HrVWlEPTB;NT60NFA2OSEQvF2=MnH1V2FPT0WU
GT3TKBMlzRS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NX3lUVJVUUN3ME21MlQ3PTl6IN88US=>NU\PRWpJW0GQR1XS
HCC2998NYmwc5I6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MmCwTWM2OD13LkS5NVA6KM7:TR?=MVfTRW5ITVJ?
NUGC-3NVnx[nl4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NUDxVFd[UUN3ME21MlQ6OzB{IN88US=>MlX0V2FPT0WU
Hs-578-TMVvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?Ml\ETWM2OD13LkWzO|k1KM7:TR?=MlO5V2FPT0WU
FADUMnG0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MYXJR|UxRTVwNUW3NlYh|ryPNUH3WoFvW0GQR1XS
NBsusSRM{TGTGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NH76RpVKSzVyPUWuOVcyPTVizszNNEfTd49USU6JRWK=
ME-180MYrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MoTWTWM2OD13LkW4NFkzKM7:TR?=MWTTRW5ITVJ?
SW1710NWG5enE2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MVnJR|UxRTVwNkG2OVQh|ryPM{LFcXNCVkeHUh?=
HuP-T3NWPCd3ZWT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NGSxU4hKSzVyPUWuOlIxOjlizszNNWWySnNxW0GQR1XS
HOSNWjEToNvT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MnXMTWM2OD13Lk[yPVI{KM7:TR?=NWe0XG1WW0GQR1XS
PA-1NV;OO3g4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MXzJR|UxRTVwNkSyOlUh|ryPM{HsR3NCVkeHUh?=
LU-99ANEL5bWJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=M4LNbGlEPTB;NT62OlQ2OSEQvF2=M4XKTXNCVkeHUh?=
RS4-11Mn71S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NYTJPFk2UUN3ME21MlY3Pzd3IN88US=>MoDSV2FPT0WU
TE-8MVrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MWrJR|UxRTVwNki1N|ch|ryPMnnnV2FPT0WU
RERF-LC-MSNGrQcVVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NYjNZmprUUN3ME21MlY5QDB|IN88US=>NXHRfXdVW0GQR1XS
MEL-JUSOMn;PS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?Ml7sTWM2OD13LkezO|gh|ryPMXnTRW5ITVJ?
SK-MES-1NHX6XplIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MnTKTWM2OD13LkizOVI5KM7:TR?=M4nDXnNCVkeHUh?=
D-263MGMm\WS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MoXKTWM2OD13Lki4N|UyKM7:TR?=NGjufZRUSU6JRWK=
NB10MnzsS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NYHGRot[UUN3ME21Mlg6PDZizszNNWPCUpV7W0GQR1XS
SK-HEP-1NXr3ZZl6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MW\JR|UxRTVwOUO0O|Eh|ryPMWnTRW5ITVJ?
HT-29NHzuXGJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MmX3TWM2OD13Lkm4NVE5KM7:TR?=NELnT3lUSU6JRWK=
KYSE-140Mn3ES5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MVfJR|UxRTZwMEKxPFIh|ryPNEn6[25USU6JRWK=
NCI-H1666MUTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MmHtTWM2OD14LkC4OFYyKM7:TR?=NWHGd4s4W0GQR1XS
NCI-H1304NXLIeYVOT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NGLKV2lKSzVyPU[uNVk6PCEQvF2=MUXTRW5ITVJ?
RPMI-8866NWqxUlNtT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=M4\qbmlEPTB;Nj6yNVMyOyEQvF2=MUDTRW5ITVJ?
MV-4-11NFv4dGtIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=M2LkWmlEPTB;Nj6yN|E6QSEQvF2=MlWwV2FPT0WU
A431M4PNOmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MkDWTWM2OD14LkK0Nlk3KM7:TR?=NIHXNJVUSU6JRWK=
PANC-10-05NVfXUpYyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MVLJR|UxRTZwMkizOlMh|ryPMXfTRW5ITVJ?
TK10MVLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NFn4clhKSzVyPU[uN|I3ODRizszNMV\TRW5ITVJ?
NCI-H1975MnHPS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?M2jHXWlEPTB;Nj60O|IyPSEQvF2=NUPO[2s2W0GQR1XS
A172MmS5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NHHmTm1KSzVyPU[uOFkyPzZizszNM1\kfnNCVkeHUh?=
D-566MGNGr2ZWVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=M{X1[2lEPTB;Nj61OFMxOyEQvF2=M4H4b3NCVkeHUh?=
NCI-H2122MYDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MWrJR|UxRTZwNkG1Nlgh|ryPMojwV2FPT0WU
COR-L105MYPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NVeyXpdqUUN3ME22MlY2Ojd3IN88US=>MmmwV2FPT0WU
AN3-CAMUXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NFuybJhKSzVyPU[uOlg3PDFizszNNISyPVZUSU6JRWK=
Calu-6NIrP[|VIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NGfzT4ZKSzVyPU[uO|k3QThizszNMnvqV2FPT0WU
HCT-116MUDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MnXRTWM2OD14LkixNlY1KM7:TR?=MonSV2FPT0WU
MHH-NB-11NXzhO|g{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MYPJR|UxRTZwOEWwNFIh|ryPMmPuV2FPT0WU
MFE-280NIX4cZRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=M3fURmlEPTB;Nj64OVk5OyEQvF2=M{i3UnNCVkeHUh?=
SW1088MWnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NHXxbZFKSzVyPU[uPVE6OTNizszNMnvvV2FPT0WU
SW48M3\4O2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7M1vYNWlEPTB;Nj65OFUyKM7:TR?=M3jZW3NCVkeHUh?=
HuCCT1MVTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NETHdlZKSzVyPUeuNFExOzdizszNNHPtS5RUSU6JRWK=
ACHNMkLsS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NGjydIRKSzVyPUeuNFI6PDNizszNNXnxUW5PW0GQR1XS
8305CNVXVU2I1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MWXJR|UxRTdwMEm5PVUh|ryPNHvOXZNUSU6JRWK=
DoTc2-4510NHPUUmtIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=M4PVN2lEPTB;Nz6xNlE2KM7:TR?=NUL2ZYFvW0GQR1XS
COR-L23Ml7yS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MUDJR|UxRTdwMkS0NkDPxE1?NGLQOVBUSU6JRWK=
SK-MEL-30NYTFU|Z5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NH7WRm9KSzVyPUeuNlUxQDNizszNMV\TRW5ITVJ?
BE-13M4rLcGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7M1y0SGlEPTB;Nz6zN|g{PCEQvF2=MUfTRW5ITVJ?
GR-STNGrNV2pIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NW[wPFlnUUN3ME23MlQxOTd2IN88US=>MmP5V2FPT0WU
LU-135M1XSOmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NXPv[3FOUUN3ME23MlU2QTN7IN88US=>NE[xdVBUSU6JRWK=
U-266MW\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?M3jPU2lEPTB;Nz61OlI5PiEQvF2=NWXtVGRKW0GQR1XS
NCI-H1355Mm\GS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?M3zxemlEPTB;Nz61PFY{PSEQvF2=NGLNSmhUSU6JRWK=
NB14M1;wdWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NIH3[4hKSzVyPUeuOlY3PDJizszNNXj5[YZlW0GQR1XS
SCC-25M2PtcWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MYHJR|UxRTdwN{C5JO69VQ>?NX:yVJByW0GQR1XS
COLO-678NIWyWI9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?=Mnf1TWM2OD15LkexNFc3KM7:TR?=M2Hxb3NCVkeHUh?=
TGBC1TKBM1rwOWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NEnkV4pKSzVyPUeuPFk{QThizszNM4XQOXNCVkeHUh?=
IST-MEL1NFnDbmVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=M4TQW2lEPTB;OD6wNFQxPiEQvF2=NITOdJZUSU6JRWK=
ECC10MWHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?Moj4TWM2OD16LkCzN|k2KM7:TR?=NEP0ZZlUSU6JRWK=
EW-16NXnXPWtMT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MXjJR|UxRThwMEi0OFUh|ryPNV33d5lDW0GQR1XS
DOHH-2MYnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MnHJTWM2OD16LkKwNFk2KM7:TR?=MYPTRW5ITVJ?
NCI-H1581MV7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MonqTWM2OD16LkK2N|I{KM7:TR?=M17VVnNCVkeHUh?=
TE-5MU\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?M3TzNGlEPTB;OD60NlQzQSEQvF2=M3fsZnNCVkeHUh?=
CAKI-1MXXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NHjy[FJKSzVyPUiuOVczOjJizszNM1\2eXNCVkeHUh?=
A673MUXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MnPNTWM2OD16Lk[zNlAzKM7:TR?=NF[yb|NUSU6JRWK=
CAL-12TNGnnTpJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=M17YdWlEPTB;OD62OVc2OyEQvF2=MWXTRW5ITVJ?
DBTRG-05MGNXXEfIR6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MmPiTWM2OD16Lke0PFU6KM7:TR?=NHH5PXdUSU6JRWK=
SK-N-FIM2LTcWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NXP3flRsUUN3ME24MlgyOzd7IN88US=>MoLJV2FPT0WU
K-562MX;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?M37YZmlEPTB;OD64N|k2PyEQvF2=M2\SNHNCVkeHUh?=
SBC-1M{HIU2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7M1qxbWlEPTB;OD64OlY1PSEQvF2=M4rTeXNCVkeHUh?=
ES4MXLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NIDxWmNKSzVyPUiuPFY5QDRizszNNYO1WGZ6W0GQR1XS
MS-1NIS3b4xIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NVjyNFlQUUN3ME24Mlg4PTF5IN88US=>M{TZS3NCVkeHUh?=
RKOMkDvS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MVTJR|UxRThwOEmwOVch|ryPNGXEW|RUSU6JRWK=
NCI-H1693NInMcWlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NXPY[VJ1UUN3ME24MlkzOTdizszNNFTYe|lUSU6JRWK=
SW954MXXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?M4OxSmlEPTB;OD65Olk4QCEQvF2=NXTEd2ZMW0GQR1XS
SK-UT-1MYrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MUPJR|UxRThwOUe2PFMh|ryPNYjIU2NNW0GQR1XS
T98GMWLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MVfJR|UxRThwOUm4OFYh|ryPMYrTRW5ITVJ?
NCI-H2126M4HoUGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NF3FVYNKSzVyPUmuNFA5OjZizszNMX;TRW5ITVJ?
TE-12NUTqVotiT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NYeyOJNsUUN3ME25MlA{OzZ5IN88US=>MVPTRW5ITVJ?
DK-MGNYDoc4l3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NIjtVXFKSzVyPUmuNlEyQTFizszNM{PUe3NCVkeHUh?=
MEG-01MVLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NFfVWYZKSzVyPUmuNlQ6OzFizszNMlXYV2FPT0WU
HCC1937NFywcVNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=Mlq2TWM2OD17LkK5NFkyKM7:TR?=MWPTRW5ITVJ?
MKN45M2OzUWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MU\JR|UxRTlwNEWwOlUh|ryPMVrTRW5ITVJ?
NCI-H1792MoLES5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MmS2TWM2OD17LkS1NlE6KM7:TR?=NIPKSXVUSU6JRWK=
SW1417NVi5ZoJoT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MVTJR|UxRTlwNU[4N|ch|ryPNFHqUpVUSU6JRWK=
639-VNU\FdFJOT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MmDzTWM2OD17Lk[0N|g5KM7:TR?=MmPiV2FPT0WU
P30-OHKNVvEeZQ4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NV[2fYJVUUN3ME25MlY2OzF4IN88US=>NYnrZY9kW0GQR1XS
YKG-1MoWxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MUnJR|UxRTlwN{WwN|Mh|ryPM4mxUnNCVkeHUh?=
KGNNH\PT2VIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NID6blZKSzVyPUmuPFM4QTVizszNMmGyV2FPT0WU
MSTO-211HMYDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?M1O0emlEPTB;OT65OVUzQSEQvF2=MWLTRW5ITVJ?
NCI-H1573NUXkOnFTT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=M4D1OGlEPTB;MUCuNVU4PCEQvF2=NGD0eJNUSU6JRWK=
NCI-H720NWL3WmJIT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MkniTWM2OD1zMD6xPVg6KM7:TR?=MVnTRW5ITVJ?
KARPAS-45MnzKS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NIS1RmFKSzVyPUGwMlI4QTVizszNNV;4eXBQW0GQR1XS
MDA-MB-175-VIIMni1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NGfSOIpKSzVyPUGwMlQ5KM7:TR?=NHLCdphUSU6JRWK=
SK-NEP-1NUXJ[|liT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MknUTWM2OD1zMD60PVgyKM7:TR?=M1LKPXNCVkeHUh?=
MKN28NUjNUppwT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=M{DOXGlEPTB;MUCuOVE5KM7:TR?=NFjmSZBUSU6JRWK=
KYSE-520NF3HOYFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MoPnTWM2OD1zMD61NkDPxE1?MVjTRW5ITVJ?
KE-37M1XKdWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MWjJR|UxRTFyLkWyO|Ih|ryPNXi2VnNzW0GQR1XS
VA-ES-BJNXvmb|QzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NFTrVJdKSzVyPUGwMlU3PyEQvF2=MYLTRW5ITVJ?
CCRF-CEMMXzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NIS1elJKSzVyPUGwMlU3QDRizszNMmrDV2FPT0WU
GMS-10NIDpbJJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NYTJR2RzUUN3ME2xNE43ODl2IN88US=>NIj2RZJUSU6JRWK=
NCI-H1623MkTyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MVfJR|UxRTFyLk[zO|kh|ryPM4LoeHNCVkeHUh?=
NEC8NF\0b3dIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MlLGTWM2OD1zMD63O|c{KM7:TR?=NIPaWFVUSU6JRWK=
MOLT-16MonyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MX;JR|UxRTFyLkixNVMh|ryPNFrWfZNUSU6JRWK=
DJM-1MWTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NHfXOWFKSzVyPUGxMlA{PzlizszNM4O3[HNCVkeHUh?=
U251MUjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NIjacWJKSzVyPUGxMlA1OiEQvF2=NFXUbItUSU6JRWK=
SBC-5M1\tUGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MUfJR|UxRTFzLkG0Olch|ryPNISzdohUSU6JRWK=
SW756MofiS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NF31d5NKSzVyPUGxMlIyPTRizszNMn7qV2FPT0WU
KS-1MoiwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?Mn\oTWM2OD1zMT6yOlE6KM7:TR?=M4DUU3NCVkeHUh?=
SF295MkLYS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MXzJR|UxRTFzLkOxNFQh|ryPMnHiV2FPT0WU
YH-13NVTMcnkxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NWrlVW1RUUN3ME2xNU4{OjZ5IN88US=>MlrQV2FPT0WU
SW837NVjvR3RuT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NFzXVlVKSzVyPUGxMlM2ODZizszNM4[3e3NCVkeHUh?=
KYSE-450M3TJfWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NVPwVHc{UUN3ME2xNU41ODV5IN88US=>MYnTRW5ITVJ?
KYSE-180NFK4N|lIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MYHJR|UxRTFzLkS4NkDPxE1?Ml;QV2FPT0WU
S-117NUjGUGZtT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MmPYTWM2OD1zMT60PFk3KM7:TR?=NYTMPW04W0GQR1XS
KOSC-2MkHTS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MXPJR|UxRTFzLk[yNlIh|ryPNWPCcoY2W0GQR1XS
KYSE-270NUjYfZZFT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NVnrOY8yUUN3ME2xNU45PzR3IN88US=>M{LmXXNCVkeHUh?=
D-336MGMkHmS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?M3zmb2lEPTB;MUGuPVA4PSEQvF2=MnjMV2FPT0WU
KALS-1MXTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MXzJR|UxRTF{LkCwNVYh|ryPMmXpV2FPT0WU
LB373-MEL-DM4nzVmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MlTiTWM2OD1zMj6wOVM{KM7:TR?=NHPLcnlUSU6JRWK=
HLENFezfFFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=Ml\MTWM2OD1zMj6wOVg2KM7:TR?=NG\rblFUSU6JRWK=
SJSA-1NHTlOJhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=M36zZ2lEPTB;MUKuNFc{PSEQvF2=NWjXPItOW0GQR1XS
SW1990NVmwToZET3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NHTyR|NKSzVyPUGyMlA6OTFizszNM2jROnNCVkeHUh?=
NOS-1M2jGPWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MU\JR|UxRTF{LkGzOVIh|ryPMlT2V2FPT0WU
GI-ME-NMnq3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NYTGRpRnUUN3ME2xNk4zOTZ|IN88US=>Mn\pV2FPT0WU
NCI-H1703NUD5dYNWT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=M2j4XWlEPTB;MUKuNlYyPiEQvF2=NXTyWY1bW0GQR1XS
ES7MU\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MX7JR|UxRTF{LkK3NlQh|ryPM4jS[nNCVkeHUh?=
KYSE-510MlfoS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NHvHZ3hKSzVyPUGyMlUxPzlizszNM{fJPHNCVkeHUh?=
BHYMnHRS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?M13FS2lEPTB;MUKuOVMxPyEQvF2=NVPUfmxXW0GQR1XS
TCCSUPM1;USGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NXvoemI4UUN3ME2xNk42PzV5IN88US=>MlPPV2FPT0WU
HSC-2MUjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MYPJR|UxRTF{LkW5PVYh|ryPNXvIU4wxW0GQR1XS
BENNXXrWIJGT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NFnNZ2FKSzVyPUGyMlYyPDNizszNMYjTRW5ITVJ?
769-PMWHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NF\TSXpKSzVyPUGyMlc6OjRizszNNGXhb2hUSU6JRWK=
HTNELkTXJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=Mon0TWM2OD1zMj64N|Q3KM7:TR?=MWTTRW5ITVJ?
LXF-289M3K3WWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MljwTWM2OD1zMj65OVMyKM7:TR?=MmrmV2FPT0WU
OVCAR-3MX;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MkO4TWM2OD1zMj65OVY4KM7:TR?=NUPpVmt6W0GQR1XS
ATN-1NV7Mfnk6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MlrLTWM2OD1zMz6wNVg1KM7:TR?=MYrTRW5ITVJ?
8-MG-BAMn;QS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MYjJR|UxRTF|LkC0OVUh|ryPNYjrSYp4W0GQR1XS
SW13NGG3OXNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NYnqNoxOUUN3ME2xN{4yOTZ3IN88US=>M{\vU3NCVkeHUh?=
NCI-H1092MULHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MUfJR|UxRTF|LkG2NkDPxE1?NH\IdJpUSU6JRWK=
OAW-42NXHsTm9GT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MXPJR|UxRTF|LkG5N|ch|ryPMoPhV2FPT0WU
NCI-H2452Mlq2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?M3:zbWlEPTB;MUOuNlE4PSEQvF2=NF7FVXZUSU6JRWK=
CAPAN-1NFvVTXRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=M4HCVGlEPTB;MUOuOVUyPCEQvF2=M{PXVnNCVkeHUh?=
NCI-H2009MVvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MVrJR|UxRTF|LkW5NVkh|ryPMmrEV2FPT0WU
SF268MU\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NHTDTGFKSzVyPUGzMlY{OjZizszNM{PC[nNCVkeHUh?=
GCIYM3fDVmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7M2LhOWlEPTB;MUOuOlkzPyEQvF2=NFrDfGZUSU6JRWK=
OS-RC-2NVvKOnVyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=M2HhVmlEPTB;MUOuPVUxOSEQvF2=NEjVPXRUSU6JRWK=
GCTMoK2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?M4ixWWlEPTB;MUOuPVY6PyEQvF2=NXrMVoN6W0GQR1XS
NB17MkLIS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NGLkd2RKSzVyPUG0MlA5PSEQvF2=MVTTRW5ITVJ?
NCI-H2030M3nkVWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MmTwTWM2OD1zND6xOFY2KM7:TR?=MY\TRW5ITVJ?
HC-1NXO5OYk3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NUXScHZVUUN3ME2xOE4zODh5IN88US=>NHf4bmtUSU6JRWK=
QIMR-WILMlrxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NES0W5ZKSzVyPUG0MlM1OTJizszNM4nqbnNCVkeHUh?=
Capan-2M1fQc2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7NH[1TZRKSzVyPUG0MlM4OTRizszNMnnUV2FPT0WU
BALL-1MlLWS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?Mm\pTWM2OD1zND60OlY2KM7:TR?=Mn;qV2FPT0WU
LS-1034MkHzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?Mk\1TWM2OD1zND62NVUzKM7:TR?=MWfTRW5ITVJ?
U-118-MGM1jyXmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7M2\YfmlEPTB;MUSuOlMyKM7:TR?=NVzibHpVW0GQR1XS
NCI-H630MoXUS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NEXXWZJKSzVyPUG0MlY2PjhizszNM{HsSnNCVkeHUh?=
OVCAR-8MlroS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MXvJR|UxRTF2LkeyNFEh|ryPNWjrbFlHW0GQR1XS
NCI-H2347NWfYZnBmT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MXzJR|UxRTF2LkiyN{DPxE1?MnftV2FPT0WU
BT-549MXPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NGrSZ3NKSzVyPUG0MlgzQDRizszNMXnTRW5ITVJ?
LB831-BLCNHHzblZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NX;rVIVIUUN3ME2xOE45QTN2IN88US=>NG\WPJhUSU6JRWK=
NCI-H661MXTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MlG2TWM2OD1zND65OVkh|ryPNHjOVoFUSU6JRWK=
MKN7MXnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NH\lXmxKSzVyPUG1MlAxQTNizszNMXvTRW5ITVJ?
U-87-MGNXz1TVVoT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MXHJR|UxRTF3LkC4PVch|ryPMnL6V2FPT0WU
OVCAR-4NInGRVlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NXfXNXNbUUN3ME2xOU4yPDJ2IN88US=>MljwV2FPT0WU
OE33NFP4dIpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NUPYO2JOUUN3ME2xOU4yPzFzIN88US=>NUjvcWJWW0GQR1XS
EC-GI-10Ml7CS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MYPJR|UxRTF3LkKzOVch|ryPMo\OV2FPT0WU
AM-38NUPiflBiT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MoDUTWM2OD1zNT6yO|E4KM7:TR?=MlXzV2FPT0WU
NCI-H1563NITWWYtIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MWfJR|UxRTF3LkO0PUDPxE1?M2Hxc3NCVkeHUh?=
SCC-4Mkf4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MWjJR|UxRTF3LkSxNFMh|ryPM{nPZnNCVkeHUh?=
Detroit562NVr6dXNwT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NXjqcIZkUUN3ME2xOU41PTR5IN88US=>MlL6V2FPT0WU
PC-14NGLVfmZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MoXTTWM2OD1zNT60PFY3KM7:TR?=M2PR[3NCVkeHUh?=
ES3M2TnU2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7M{TvNGlEPTB;MUWuOVM3KM7:TR?=MWnTRW5ITVJ?
OCI-AML2M1fYcmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MnqwTWM2OD1zNT63OlE1KM7:TR?=NXv1dYNUW0GQR1XS
LU-134-ANFPsUJhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MXjJR|UxRTF3LkmwNVgh|ryPMWTTRW5ITVJ?
SASNWrMWY93T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MWrJR|UxRTF3LkmzO|Mh|ryPM2f6NnNCVkeHUh?=
TGBC11TKBMkCzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NIXuR4RKSzVyPUG1Mlk1OTRizszNM1zne3NCVkeHUh?=
HOP-62MV;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NEDtd2JKSzVyPUG1Mlk2QTdizszNNEnE[HZUSU6JRWK=
G-401NFT3OXFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NYTYfYp{UUN3ME2xOU46PjR7IN88US=>NGjDenVUSU6JRWK=
NCI-H28M{fp[Gdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NEj0TpVKSzVyPUG2MlA5PTZizszNM3GwVnNCVkeHUh?=
A204NIXhO5lIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MkDSTWM2OD1zNj6yNFA3KM7:TR?=MYPTRW5ITVJ?
NCI-H1299NGq3dHpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=M2HsXmlEPTB;MU[uNlI6OSEQvF2=M2rDcHNCVkeHUh?=
VMRC-RCZMV3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MWTJR|UxRTF4LkK1PVIh|ryPNVPPfItLW0GQR1XS
BxPC-3M3LwOWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MX;JR|UxRTF4LkK4OVYh|ryPMXfTRW5ITVJ?
NCI-H2228MULHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NGDWUVVKSzVyPUG2MlUyPThizszNNIHObopUSU6JRWK=
NCI-H23NEnnSZBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NIfjWYhKSzVyPUG2MlYxPzhizszNNFT3V|RUSU6JRWK=
NKM-1NXz6O4FoT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NYCwV|l5UUN3ME2xO{4xOTh7IN88US=>NGHCTlJUSU6JRWK=
KYSE-70M3zzTmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MYjJR|UxRTF5LkK4PUDPxE1?NH;ydXlUSU6JRWK=
BB49-HNCNYjiWYdmT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NYPPc2F[UUN3ME2xO{42Pjh4IN88US=>MYDTRW5ITVJ?
SCC-15M1TiSWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NHjoXVJKSzVyPUG3Mlg1PzNizszNMUDTRW5ITVJ?
D-247MGNX6zNIE1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NYLCRVlyUUN3ME2xO{46OjR5IN88US=>MWrTRW5ITVJ?
BB30-HNCM1XuOGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7M4LYN2lEPTB;MUiuNFMyQCEQvF2=NX:xR3JPW0GQR1XS
CAL-85-1M1vKc2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7MXvJR|UxRTF6LkG4NFkh|ryPNYHhcFVMW0GQR1XS
HT-3MYLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NYLUOIlmUUN3ME2xPE4{QTd5IN88US=>M4XxcnNCVkeHUh?=
KYSE-410MmTZS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MkSxTWM2OD1zOD60OVc4KM7:TR?=NVzCWlR6W0GQR1XS
SW982NVi1e441T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NXfINWVLUUN3ME2xPE42PjR7IN88US=>NV;6WlM5W0GQR1XS
SW962MUXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NVPZUY1rUUN3ME2xPE42PzB{IN88US=>NF\JVFFUSU6JRWK=
Ramos-2G6-4C10NWDWWZJ5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=M4q3V2lEPTB;MUiuOVkzPyEQvF2=M36xZXNCVkeHUh?=
OC-314NGfyZnJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MkPQTWM2OD1zOD63N|g1KM7:TR?=NVzreVVLW0GQR1XS
LS-123M1\MWWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7M{TpdmlEPTB;MUiuO|kxOSEQvF2=MYLTRW5ITVJ?
D-502MGMU\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NFTmTHlKSzVyPUG4MlgyOzlizszNMnLsV2FPT0WU
RO82-W-1NV7EWWhjT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NXLNN4RSUUN3ME2xPE45Ojh6IN88US=>MkDMV2FPT0WU
HuO9MVLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NHfEXWJKSzVyPUG5MlE{PzlizszNNE[2OYFUSU6JRWK=
ETK-1NGflb4NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MnjRTWM2OD1zOT6xPFI4KM7:TR?=MVvTRW5ITVJ?
SNU-387M1va[2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7M3K4Z2lEPTB;MUmuNVg5QSEQvF2=M2LXSnNCVkeHUh?=
SW1573M4HiV2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7NFK2fWpKSzVyPUG5MlE6PjlizszNNHvrbpBUSU6JRWK=
NTERA-S-cl-D1NXLESZRyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NWjVdHh7UUN3ME2xPU4zODB5IN88US=>NVnxPW45W0GQR1XS
SF126NUD6doduT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NF2wRplKSzVyPUG5MlM2ODJizszNM3vkWHNCVkeHUh?=
Calu-3MojSS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MoO4TWM2OD1zOT60NlM4KM7:TR?=NITYU4NUSU6JRWK=
NCI-H1048Ml7SS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NGnvTWZKSzVyPUKwMlMzPjZizszNMYTTRW5ITVJ?
NCI-H226NUjjfopCT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NUj6UGlnUUN3ME2yNE41Ozl7IN88US=>MonpV2FPT0WU
FTC-133NXvGUJZET3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=M1ThfGlEPTB;MkCuOFcxOyEQvF2=NYPKbWdMW0GQR1XS
SF539M{PyRWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NIXRd49KSzVyPUKwMlUyPzJizszNNH:5[|JUSU6JRWK=
TE-6NEXk[npIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=Mny3TWM2OD1{MD64NFY4KM7:TR?=MmfrV2FPT0WU
UMC-11M{DYT2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7MVfJR|UxRTJyLkmxOlQh|ryPMUXTRW5ITVJ?
BeckerM1HSWmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MUDJR|UxRTJzLkGxNVgh|ryPM3LVOnNCVkeHUh?=
KP-4MUjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MV\JR|UxRTJzLkGxPVYh|ryPNGfCPJZUSU6JRWK=
ChaGo-K-1Mle2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NUK2U3lsUUN3ME2yNU4{PjJ5IN88US=>NYLneVRnW0GQR1XS
CFPAC-1M1uxOmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7M33RWGlEPTB;MkGuN|g2QCEQvF2=NUHZeW9KW0GQR1XS
A498MX3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NELiS2NKSzVyPUKxMlU{OTJizszNNGD2dXJUSU6JRWK=
NCI-H1755MoTLS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?M{TnbWlEPTB;MkGuOlc1OSEQvF2=MVfTRW5ITVJ?
TI-73MnToS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NETrdGRKSzVyPUKyMlMzQCEQvF2=MWDTRW5ITVJ?
NCI-H441MnW4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MmO3TWM2OD1{Mj61Olg6KM7:TR?=MmT4V2FPT0WU
CaR-1NXXtXFh5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NXjJN5VtUUN3ME2yN{4xOjF|IN88US=>NIfVUXNUSU6JRWK=
HCC1806MkHOS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NF\XbWdKSzVyPUKzMlA2QDNizszNMmTEV2FPT0WU
SNU-449NV\0T2FzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NIH3[pFKSzVyPUKzMlMzQSEQvF2=MnvBV2FPT0WU
EKVXM{[1W2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7MnLPTWM2OD1{Mz6zPVA6KM7:TR?=NGPVfXdUSU6JRWK=
DMS-114MmHES5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NIXEbIpKSzVyPUKzMlU4PjVizszNM2roXnNCVkeHUh?=
A704NFXvS5dIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=Mk[yTWM2OD1{Mz62NVA{KM7:TR?=NX73SlNSW0GQR1XS
LC-2-adMYDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NITNU5dKSzVyPUKzMlYyPDdizszNMYXTRW5ITVJ?
VM-CUB-1MV;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MUTJR|UxRTJ|LkezOFEh|ryPMX3TRW5ITVJ?
PC-3MoLWS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NYrpTVBvUUN3ME2yOE4xPTJ4IN88US=>NGLUSoJUSU6JRWK=
HELNFzJd4hIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MoXZTWM2OD1{ND6wPFY2KM7:TR?=M1XpXXNCVkeHUh?=
ABC-1NHfKTlVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MkS5TWM2OD1{ND6yO|I6KM7:TR?=Mmf3V2FPT0WU
COLO-680NNGS1W2tIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NGPlZVNKSzVyPUK0MlQ4PjRizszNMmDEV2FPT0WU
MZ1-PCNGDaelBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NVzv[4R3UUN3ME2yOE43QDdizszNM{jWcXNCVkeHUh?=
NCI-H69M4j3dGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MWDJR|UxRTJ2LkezOVQh|ryPNFLQfWRUSU6JRWK=
TE-1NGLiW5dIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NILjUmhKSzVyPUK1MlA1QTlizszNNFvBco9USU6JRWK=
EW-3M1zOeWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7M122O2lEPTB;MkWuNVE{KM7:TR?=Mom2V2FPT0WU
PANC-08-13M4SxdGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MmHlTWM2OD1{NT64NVA{KM7:TR?=NVvITWFQW0GQR1XS
NMC-G1NH\3UIhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=M{DZbmlEPTB;Mk[uNFA5QCEQvF2=MXPTRW5ITVJ?
BT-20MXLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NGexXW1KSzVyPUK2MlQ2PDNizszNMlnuV2FPT0WU
TGBC24TKBMn;NS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NFvyXlFKSzVyPUK2Mlc{OzFizszNNV3oc|ZuW0GQR1XS
TE-11MknZS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NVTRUpdUUUN3ME2yOk46QDl3IN88US=>MlfwV2FPT0WU
ESS-1NHv2RoFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=M1LjfWlEPTB;MkeuN|IyPiEQvF2=MVnTRW5ITVJ?
JVM-3NWXRU|llT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NFHZZ5hKSzVyPUK3MlY1PzVizszNMWPTRW5ITVJ?
C3AMkfHS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?M{jWemlEPTB;MkeuPFQ6PiEQvF2=MWHTRW5ITVJ?
MDA-MB-157NHHQNGVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NWjrbYJrUUN3ME2yO{45PzV|IN88US=>MVHTRW5ITVJ?
KLENGPLSoVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MnvYTWM2OD1{OD6xNFU5KM7:TR?=MVXTRW5ITVJ?
ES1Mkn1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?M323U2lEPTB;MkiuNVg{QCEQvF2=NG[yVXJUSU6JRWK=
CAL-120M2P4emdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MY\JR|UxRTJ6LkO5PVkh|ryPM4raTXNCVkeHUh?=
NCI-N87Mmf6S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?M2fv[2lEPTB;MkiuOVExPSEQvF2=M33OWnNCVkeHUh?=
RPMI-8226M4LUR2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7MojHTWM2OD1{OT6xPFQ{KM7:TR?=NF:3S5JUSU6JRWK=
COR-L88NX73cYNyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NHXIXW5KSzVyPUK5MlI1OTlizszNMnXGV2FPT0WU
UACC-893NFnlNYxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MX7JR|UxRTJ7LkOxN|ch|ryPM17lWnNCVkeHUh?=
C8166NX7pXXRKT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NELTeFBKSzVyPUK5Mlk6QTZizszNM33IcHNCVkeHUh?=
J82M1fENGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MkDDTWM2OD1|MD64NVQ4KM7:TR?=M4X5O3NCVkeHUh?=
PFSK-1M3jaPGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NVK0b5JkUUN3ME2zNU4xPjV7IN88US=>M4XjNHNCVkeHUh?=
COLO-684NWrFOZczT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NX3lUHhtUUN3ME2zNU41Ozd2IN88US=>NFTpOJZUSU6JRWK=
CAL-72NITwdINIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MWnJR|UxRTNzLkW3Nlkh|ryPMnX3V2FPT0WU
SNB75MnGyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NVTBeZhkUUN3ME2zNU45QTdizszNMW\TRW5ITVJ?
MDA-MB-415MmjzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?M{jLZ2lEPTB;M{GuPVc3OiEQvF2=NITzeHVUSU6JRWK=
SiHaMl7vS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NIe4d|NKSzVyPUOyMlQ4OTFizszNMYHTRW5ITVJ?
NCI-H1648NVTaRZBRT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MVnJR|UxRTN{LkmzOFUh|ryPNH7ENXhUSU6JRWK=
EFO-21M4\rRWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MVzJR|UxRTN|LkCwOUDPxE1?NIPrbFVUSU6JRWK=
HCC38MYnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?M3\0V2lEPTB;M{OuN|g1OSEQvF2=MUDTRW5ITVJ?
IA-LMMkDGS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MkXtTWM2OD1|Mz63PFg6KM7:TR?=NXXHUmhRW0GQR1XS
CTV-1NHjLRnNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MoXwTWM2OD1|Mz65O|g3KM7:TR?=MWfTRW5ITVJ?
NCI-H446Mlu0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MYjJR|UxRTN2LkK2PFkh|ryPNFzJUXJUSU6JRWK=
IST-SL1MXXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?M2XWTmlEPTB;M{SuO|QxQCEQvF2=NV;ETJdpW0GQR1XS
EW-22MkjKS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MVjJR|UxRTN2Lke3OVkh|ryPM4HVe3NCVkeHUh?=
JEG-3NUjxSJhjT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NIDVPJZKSzVyPUO2MlE4PjZizszNNHjrR2tUSU6JRWK=
LU-65NXT4fYRVT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NYG1eW5NUUN3ME2zOk4zQTh3IN88US=>NUTEVY51W0GQR1XS
NCI-H596MXLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MkfGTWM2OD1|Nj65OVkyKM7:TR?=NXjGVlZrW0GQR1XS
KNS-81-FDNWDCcG5nT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MnvXTWM2OD1|Nz6xOFUh|ryPNHzDbFFUSU6JRWK=
NCI-H1793MkTkS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?M1:0O2lEPTB;M{euO|A5PiEQvF2=NVLYd|NFW0GQR1XS
NCI-H460NVPSZ2xGT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=Mn\nTWM2OD1|OD6wPFc{KM7:TR?=NVG4UlA{W0GQR1XS
MPP-89MlL5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MYfJR|UxRTN7LkW4PFYh|ryPNXLEWnFGW0GQR1XS
D-542MGNHTwd|NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NXnMfldlUUN3ME2zPU45PDN4IN88US=>NUDyc4FRW0GQR1XS
JARMVPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MXLJR|UxRTRyLkS3NFUh|ryPM13ReHNCVkeHUh?=
NCI-H209MYHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NFP2VGtKSzVyPUSwMlY4PyEQvF2=M4nu[nNCVkeHUh?=
G-402NU[1OpBWT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NIG2VGlKSzVyPUSxMlM6QTNizszNMoj1V2FPT0WU
IST-MES1MmqwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MWjJR|UxRTR{LkG5N|Uh|ryPNWG2ZWhFW0GQR1XS
DaoyMXvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NUXZXXlUUUN3ME20Nk42PDdzIN88US=>MWPTRW5ITVJ?
EW-11M1XrWGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MUTJR|UxRTR|LkGyNVEh|ryPNUnpSHZDW0GQR1XS
Saos-2NVjP[VY1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=M2HRWGlEPTB;NEOuNVU{PyEQvF2=NFKwNHdUSU6JRWK=
no-10M2PK[mdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NV3iNY1VUUN3ME20N{4yPzB{IN88US=>MkS4V2FPT0WU
HCC1395MkXxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?M{C1N2lEPTB;NEOuOFY1PCEQvF2=MYDTRW5ITVJ?
HCE-4MlvMS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MmPiTWM2OD12Mz63OlY1KM7:TR?=MXfTRW5ITVJ?
EW-1NF32N3lIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=M4jGVmlEPTB;NEOuPFA1QSEQvF2=NV\KRVI6W0GQR1XS
OCUB-MMX;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NVXwUpR7UUN3ME20OE4{PjN6IN88US=>MWDTRW5ITVJ?
IGR-1MljYS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MXTJR|UxRTR2LkSxNVUh|ryPM3:2O3NCVkeHUh?=
NCI-H1838NVm3fG4yT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MUjJR|UxRTR2LkSzOFkh|ryPM1OzeXNCVkeHUh?=
NCI-H2405NUnvRmZNT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NXLzOnllUUN3ME20OE42OzRizszNNH34VnVUSU6JRWK=
GB-1MmnhS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?M2TkOWlEPTB;NESuO|Q3OyEQvF2=NFHvWYlUSU6JRWK=
MG-63M{HJU2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7M4DJZ2lEPTB;NE[uNFY6PiEQvF2=NWjGTHZGW0GQR1XS
KP-N-YNNHe3SHhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MVjJR|UxRTR4LkS2O|kh|ryPNHrvW2lUSU6JRWK=
no-11NYjpOWtYT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MofMTWM2OD12Nz6wNlQ1KM7:TR?=Mo\LV2FPT0WU
SW948M4jmV2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7M{PYe2lEPTB;NEeuN|M4PyEQvF2=MlTFV2FPT0WU
CAMA-1MkXjS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MoXUTWM2OD12Nz6zOFM5KM7:TR?=M2jjNXNCVkeHUh?=
HCC1187NF\vW|hIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NFnaT3dKSzVyPUS3MlUyKM7:TR?=NFfBXWlUSU6JRWK=
D-392MGM37jfWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NHHoZmhKSzVyPUS3MlY2OTZizszNMlrNV2FPT0WU
647-VMlHXS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?M4[5W2lEPTB;NEmuN|QyPCEQvF2=MU\TRW5ITVJ?

... Click to View More Cell Line Experimental Data

In vivo Oral dosing of CI-1040 impairs the growth of colon tumor xenografts of mouse and human with a wide dose range of 48-200 mg/kg per dose, but not of P388 leukemia. [1] CI-1040 inhibits the tumor xenografts from PTC cells carrying a BRAF mutation with 31.3% reduction, carrying the RET/PTC1 rearrangement with 47.5% reduction than in untreated (vehicle) mice after 3 weeks of oral administration (300 mg/kg/d). No toxic effects are observed in any mice when they are treated with CI-1040. [2] Transient exposure of mammary tumors to CI-1040 and UCN-01 causes tumor cell death in vivo and prolonged suppression of tumor regrowth. Combined treatment with CI-1040 (25 mg/kg) and UCN-01 (0.1-0.2 mg/kg) significantly reduces MDA-MB-231, and largely abolishs MCF7 tumor growth in implanted athymic mice, while either single treatment has no significant activity. The drug combination leads to profound tumor cell death which correlates with a reduction in the phosphorylation of ERK1/2 and the immuno-reactivity of Ki67 and of CD31. [5]
Features First MEK inhibitor to begin clinical development.

Protocol(Only for Reference)

Kinase Assay:

[2]

MEK1 Assay MAP kinase is activated after phosphorylation by MEK; the activated MAP kinase subsequently phosphorylates myelin basic protein (MBP).Incorporation of 32P into myelin basic protein (MBP) is assayed in the presence of glutathione S-transferase (GST) fusion proteins containing the 44-kDa MAPK (GST-MAPK) or the 45-kDa MEK (GST-MEK1). Assays are conducted in 50μL of 50 mM Tris, pH 7.4/10 mM MgCl2 /2 mM EGTA/10 μM [γ-32P]ATP containing 10 μg of GST-MEK1, 0.5 μg of GST-MAPK, and 40 μg of MBP. After incubation at 30°C for 15 minutes, reactions are stopped by addition of Laemmli SDS sample buffer. Phosphorylated MBP is resolved by SDS/10% PAGE. This screening effort leads to the discovery of several small-molecule inhibitors of MEK, i.e. CI-1040. Experiments assessing the order of addition shows that CI-1040 directly inhibits MEK1 with a 50% inhibitory concentration (IC50) of 17 nM, without affecting the activity of MAPK.

Cell Assay:

[1]

Cell lines Colon 26 carcinoma cells
Concentrations 0.1-10 μM
Incubation Time 24 hours
Method

Cells are planted seeded in T-75 cm 2 flasks and treated the next day for 24 hous with either DMSO or CI-1040. Single-cell suspensions are collected, and pellets are fixed in ice-cold ethanol (70%) for 30 minutes. After centrifugation of the samples, propidium iodide (50 μg/mL) and RNase (30 units/mL) are added to the pellets for 20 minutes at 37 °C. After filtration, samples are analyzed by flow cytometry.

Animal Study:

[3]

Animal Models PTC cells in athymic mice
Formulation Cremophor EL–95% ethanol (50:50) and dilutes with water
Dosages 150 mg/kg
Administration Orally twice daily

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDog
Weight (kg)0.020.151.80.40.0810
Body Surface Area (m2)0.0070.0250.150.050.020.5
Km factor36128520
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

References

[1] Sebolt-Leopold JS, et al. Nat Med, 1999, 5(7), 810-816.

[2] Davies SP, et al. Biochem J, 2000, 135(1), 95-105.

view more

Clinical Trial Information( data from http://clinicaltrials.gov, updated on 2016-01-10)

NCT Number Recruitment Conditions Sponsor
/Collaborators
Start Date Phases
NCT00033384 Completed Breast Cancer|Colorectal Cancer|Lung Cancer|Pancreatic Cancer University of Alabama at Birmingham|National Cancer Insti  ...more University of Alabama at Birmingham|National Cancer Institute (NCI) February 2002 Phase 2
NCT00034827 Completed Colorectal Neoplasms|Breast Neoplasms|Carcinoma, Non-Small-Cell Lung|Pancreatic Neoplasms Pfizer January 2002 Phase 2

Chemical Information

Download PD184352 (CI-1040) SDF
Molecular Weight (MW) 478.67
Formula

C17H14ClF2IN2O2

CAS No. 212631-79-3
Storage 3 years -20℃powder
6 months-80℃in solvent
Synonyms N/A
Solubility (25°C) * In vitro DMSO 96 mg/mL (200.55 mM)
Ethanol 14 mg/mL (29.24 mM)
Water <1 mg/mL (<1 mM)
In vivo 30% PEG400/0.5% Tween80/5% propylene glycol, pH 9 10 mg/mL
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
Chemical Name 2-(2-chloro-4-iodophenylamino)-N-(cyclopropylmethoxy)-3,4-difluorobenzamide

Customer Product Validation (12)


Click to enlarge
Rating
Source Science 2011 331, 912-916. PD184352 (CI-1040) purchased from Selleck
Method Immunohistochemistry
Cell Lines Hand2d/d mice
Concentrations
Incubation Time 24h
Results The epithelia of vehicle-treated horn showed prominent expression of p-FRS2 and p-ERK1/2(Fig.A,a and c). However, the levels of both p -FRS2 and p -ERK1/2 were reduced in the epithelia of PD173074-treated horn on day 4 of pregnancy (Fig. A, b and d). We also observed a marked decline in the proliferative activity of Hand2-null uterine epithelia, as indicated by decreased Ki-67 staining (Fig. A, e and f) . In parallel experiments, administration of PD184352, an inhibitor of the ERK1/2 pathway, to uterine horns of Hand2 d/d mice suppressed the level of pERK1/2 (Fig.B, a and b) , as well as luminal epithelial proliferation ( Fig. B, c and d).The ERK1/2-dependent phosphorylation of epithelial ERα at Ser118 is critical for the transcriptional activation of ERα. Administration of either PD173074 (Fig. C, a to d) or PD184352 (Fig. C, e to h) to Hand2-null uterine horns blocked the phosphorylation of epithelial ERα at Ser118 and the expression of Muc -1.

Click to enlarge
Rating
Source J Natl Cancer Inst 2012 104(21), 1673-9. PD184352 (CI-1040) purchased from Selleck
Method Western Blot
Cell Lines primary human melanocytes
Concentrations 1 uM
Incubation Time 18 h
Results In BRAFV600E melanoma cells, the highly selective BRAFV600E inhibitor GDC-0879 and three selective MEK inhibitors [PD184352/CI-1040, U0126, PD98059] did not suppress c-Jun levels, although they effectively reduced phospho-ERK levels.

Click to enlarge
Rating
Source J Natl Cancer Inst 2012 104(21), 1673-9. PD184352 (CI-1040) purchased from Selleck
Method Xenograft
Cell Lines athymic nude Foxn1nu mice
Concentrations 3 mg/kg
Incubation Time 13 day
Results CDK2/4 inhibition augmented statistically significant growth reduction of melanoma xenografts in vivo by the BRAF and MEK inhibitors (GDC-0879 and CI1040).

Click to enlarge
Rating
Source Proc Natl Acad Sci U S A 2011 108, 16392-7. PD184352 (CI-1040) purchased from Selleck
Method Western blot
Cell Lines DU145/PC3 cells
Concentrations 10 μM
Incubation Time 12 h
Results PI3K inhibition by LY294002 in-creased ERK activation in Her2-overexpressing DU145 cells, whereas treatment with the MEK inhibitor PD184352 in PC3 cells with Her2 overexpression resulted in increased AKT activation. This suggests a strong reciprocal feedback regulation of the PI3K/AKT and MEK/ERK signaling cascades (Fig. E)

Click to enlarge
Rating
Source Breast Cancer Res 2011 13, R36. PD184352 (CI-1040) purchased from Selleck
Method MTT assay
Cell Lines MDA-MB-453 cell line, HCC-1954 cell line
Concentrations 2-25 μM
Incubation Time 48 h
Results We observed that monotherapies with CI-1040 and other inhibitors reduced cell viability in a dose-dependent manner across these cell lines

Click to enlarge
Rating
Source Breast Cancer Res 2011 13, R36. PD184352 (CI-1040) purchased from Selleck
Method MTT assay/Western blot
Cell Lines MDA-MB-453-R cell line
Concentrations 5/10 μM
Incubation Time 48 h
Results "Flutamide and CI-1040 treatments were carried out at the same four dose combinations applied before in the nonresistant line (CI-1040(5μM)/flutamide(5μM), CI-1040 (10μM) /flutamide (5μM), CI-1040 (5μM)/flutamide (10μM), and CI-1040(10 μM)/f lutamide (10μM)). Importantly, we observed a synergy at all four dose combinations in MDA -MB-453-R line with CI values of 0.68 to 0.76 (Figure D). Combination therapies with CI-1040 (5μM)/f lutamide (5μM) and CI-1040 (5μM)/flutamide (10μM) completely abrogated ERK phosphorylationin MDA-MB-453-R line (Figure F).

Click to enlarge
Rating
Source Neoplasia 2011 13, 154–166. PD184352 (CI-1040) purchased from Selleck
Method Western blot
Cell Lines MDA-MB-453 cell lines, HCC-1954 cell lines
Concentrations 10 μM
Incubation Time 24 h
Results We observed that CI-1040 at 10μM concentration almost completely inhibited ERK phosphorylation in both cell lines

Click to enlarge
Rating
Source Neoplasia 2011 13, 154–166. PD184352 (CI-1040) purchased from Selleck
Method RT-PCR
Cell Lines MDA-MB-453 cell lines, HCC-1954 cell lines
Concentrations 10 μM
Incubation Time 24 h
Results We assessed AR expression using RT-PCR and observed a significant reduction of AR transcript level after MEK inhibition by CI-1040 to 0.2- and 0.6-fold in MDA-MB- 453 and HCC-1954 cells, respectively, compared with the controls (P < .01; Figure A). This finding suggest that ERK signaling regulates AR expression in molecular apocrine cells.

Click to enlarge
Rating
Source Neoplasia 2011 13, 154–166. PD184352 (CI-1040) purchased from Selleck
Method MTT assay
Cell Lines MDA-MB-453 cell line, HCC-1954 cell line, HCC-202 cell line
Concentrations 5/10 μM
Incubation Time 48 h
Results These data suggest that AR inhibitor flutamide and MEK inhibit or CI-1040 have synergy in reducing cell viability of molecular apocrine cell lines.

Click to enlarge
Rating
Source 2010 Dr. Zhang of Tianjin Medical University. PD184352 (CI-1040) purchased from Selleck
Method Western blot
Cell Lines Breast cancer cells
Concentrations 0-10 nM
Incubation Time 3 h
Results

Click to enlarge
Rating
Source 2010 Dr. Zhang of Tianjin Medical University. PD184352 (CI-1040) purchased from Selleck
Method Western blot
Cell Lines Breast cancer cells
Concentrations 0-1 nM
Incubation Time 3 h
Results

Click to enlarge
Rating
Source 2010 Dr. Shuo Dong of Baylor College of Medicine. PD184352 (CI-1040) purchased from Selleck
Method Cell colony formation assays
Cell Lines primary hematopoietic cells
Concentrations 10 μM
Incubation Time
Results

Product Use Citation (41)

Tech Support & FAQs

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

* Indicates a Required Field

Related MEK Products

  • Cobimetinib (GDC-0973, RG7420)

    Cobimetinib (GDC-0973, RG7420) is a potent and highly selective MEK1 inhibitor with IC50 of 4.2 nM. Phase 3.

  • BI-847325

    BI-847325 is an orally bioavailable, and selective dual MEK/Aurora kinase inhibitor with IC50 of 3 nM, 25 nM, 15 nM, 25 nM, and 4 nM for Xenopus laevis Aurora B, human Aurora A and Aurora C, as well as human MEK1 and MEK2, respectively. Phase 1.

  • GDC-0623

    GDC-0623 is a potent and ATP-uncompetitive MEK1 inhibitor with Ki of 0.13 nM. Phase 1.

  • Trametinib (GSK1120212)

    Trametinib (GSK1120212) is a highly specific and potent MEK1/2 inhibitor with IC50 of 0.92 nM/1.8 nM in cell-free assays, no inhibition of the kinase activities of c-Raf, B-Raf, ERK1/2.

    Features:More potent than PD0325901 or AZD6244.

  • PD0325901

    PD0325901 is a selective and non ATP-competitive MEK inhibitor with IC50 of 0.33 nM in cell-free assays, roughly 500-fold more potent than CI-1040 on phosphorylation of ERK1 and ERK2. Phase 2.

  • Selumetinib (AZD6244)

    Selumetinib (AZD6244) is a potent, highly selective MEK1 inhibitor with IC50 of 14 nM in cell-free assays, also inhibits ERK1/2 phosphorylation with IC50 of 10 nM, no inhibition to p38α, MKK6, EGFR, ErbB2, ERK2, B-Raf, etc. Phase 3.

    Features:First MEK inhibitor being tested in Phase II clinical trials.

  • U0126-EtOH

    U0126-EtOH is a highly selective inhibitor of MEK1/2 with IC50 of 0.07 μM/0.06 μM in cell-free assays, 100-fold higher affinity for ΔN3-S218E/S222D MEK than PD98059.

    Features:A chemically synthesized and highly selective inhibitor of both MEK1 and MEK2.

  • PD98059

    PD98059 is a non-ATP competitive MEK inhibitor with IC50 of 2 μM in a cell-free assay, specifically inhibits MEK-1-mediated activation of MAPK; does not directly inhibit ERK1 or ERK2.

    Features:Does not inhibit c-Raf phosphorylated MEK1.

  • Binimetinib (MEK162, ARRY-162, ARRY-438162)

    Binimetinib (MEK162, ARRY-162, ARRY-438162) is a potent inhibitor of MEK1/2 with IC50 of 12 nM in a cell-free assay. Phase 3.

  • Refametinib (RDEA119, Bay 86-9766)

    Refametinib (RDEA119, Bay 86-9766) is a potent, ATP non-competitive and highly selective inhibitor of MEK1 and MEK2 with IC50 of 19 nM and 47 nM, respectively.

Recently Viewed Items

Tags: buy PD184352 (CI-1040) | PD184352 (CI-1040) supplier | purchase PD184352 (CI-1040) | PD184352 (CI-1040) cost | PD184352 (CI-1040) manufacturer | order PD184352 (CI-1040) | PD184352 (CI-1040) distributor
×
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
Contact Us