PD184352 (CI-1040)

Catalog No.S1020

For research use only.

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. PD184352 (CI-1040) selectively induces apoptosis. Phase 2.

PD184352 (CI-1040) Chemical Structure

CAS No. 212631-79-3

Selleck's PD184352 (CI-1040) has been cited by 128 publications

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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. PD184352 (CI-1040) selectively induces apoptosis. Phase 2.
Features First MEK inhibitor to begin clinical development.
Targets
MEK1 [1]
(Cell-free assay)
MEK2 [1]
(Cell-free assay)
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 Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
PC-3 NFm0ZZpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mk\xTWM2OD1{ND6wOVI3KM7:TR?= MmW1QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVA2PDR{Lze+V2FPT0WUPD;hQi=>
VM-CUB-1 NInjb|dIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIGw[HJKSzVyPUKzMlc{PDFizszN M4\aXFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFExPTR2Mj:nQnNCVkeHUkyvZV4>
LC-2-ad MomwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlTxTWM2OD1{Mz62NVQ4KM7:TR?= MmfsQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVA2PDR{Lze+V2FPT0WUPD;hQi=>
A704 MVXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NF3z[HZKSzVyPUKzMlYyODNizszN MljxQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVA2PDR{Lze+V2FPT0WUPD;hQi=>
DMS-114 MUPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVXJR|UxRTJ|LkW3OlUh|ryP M2PDVVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFExPTR2Mj:nQnNCVkeHUkyvZV4>
EKVX Mo\nS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWXvNpdDUUN3ME2yN{4{QTB7IN88US=> MXO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNFU1PDJxJ{7TRW5ITVJ:L3G+
SNU-449 NVywPGRsT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1PLUGlEPTB;MkOuN|I6KM7:TR?= MWC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNFU1PDJxJ{7TRW5ITVJ:L3G+
HCC1806 MUTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWPJR|UxRTJ|LkC1PFMh|ryP M3LDbFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFExPTR2Mj:nQnNCVkeHUkyvZV4>
CaR-1 MWfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MUHJR|UxRTJ|LkCyNVMh|ryP NEDRWpY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyODV2NEKvK|5USU6JRWK8M4E,
NCI-H441 NGD2[4xIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{SyZ2lEPTB;MkKuOVY5QSEQvF2= M2fiOlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFExPTR2Mj:nQnNCVkeHUkyvZV4>
TI-73 NGXRXXpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnvnTWM2OD1{Mj6zNlgh|ryP MUW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNFU1PDJxJ{7TRW5ITVJ:L3G+
NCI-H1755 MoryS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4eybWlEPTB;MkGuOlc1OSEQvF2= M3HLbFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFExPTR2Mj:nQnNCVkeHUkyvZV4>
A498 MYjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2rQTWlEPTB;MkGuOVMyOiEQvF2= M{npVlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFExPTR2Mj:nQnNCVkeHUkyvZV4>
CFPAC-1 NI[4fXlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXLJR|UxRTJzLkO4OVgh|ryP M4[ybVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFExPTR2Mj:nQnNCVkeHUkyvZV4>
ChaGo-K-1 M4DwNmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2jZfmlEPTB;MkGuN|YzPyEQvF2= MnyzQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVA2PDR{Lze+V2FPT0WUPD;hQi=>
KP-4 NYDm[Yc4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnfFTWM2OD1{MT6xNVk3KM7:TR?= MkS5QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVA2PDR{Lze+V2FPT0WUPD;hQi=>
Becker M{fJT2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{jLOWlEPTB;MkGuNVEyQCEQvF2= M{fmVVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFExPTR2Mj:nQnNCVkeHUkyvZV4>
UMC-11 NVzNTIt[T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYr1cmtNUUN3ME2yNE46OTZ2IN88US=> NE\KV2U9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyODV2NEKvK|5USU6JRWK8M4E,
TE-6 MUjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MonITWM2OD1{MD64NFY4KM7:TR?= NYHHNVR7RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTB3NESyM{c,W0GQR1XSQE9iRg>?
SF539 Ml:0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NI\B[oNKSzVyPUKwMlUyPzJizszN NV\sTnNTRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTB3NESyM{c,W0GQR1XSQE9iRg>?
FTC-133 NHLCbZBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGLVOYpKSzVyPUKwMlQ4ODNizszN MWi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNFU1PDJxJ{7TRW5ITVJ:L3G+
NCI-H226 MmTKS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUnJR|UxRTJyLkSzPVkh|ryP MYS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNFU1PDJxJ{7TRW5ITVJ:L3G+
NCI-H1048 NHHCU5VIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnvITWM2OD1{MD6zNlY3KM7:TR?= M3H4c|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFExPTR2Mj:nQnNCVkeHUkyvZV4>
Calu-3 M2XZe2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmfZTWM2OD1zOT60NlM4KM7:TR?= NVjWZm9iRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTB3NESyM{c,W0GQR1XSQE9iRg>?
SF126 MmTYS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVzJR|UxRTF7LkO1NFIh|ryP MmPOQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVA2PDR{Lze+V2FPT0WUPD;hQi=>
NTERA-S-cl-D1 NILMPJNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mlf3TWM2OD1zOT6yNFA4KM7:TR?= MXy8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNFU1PDJxJ{7TRW5ITVJ:L3G+
SW1573 NF\adYFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYXJR|UxRTF7LkG5Olkh|ryP M1XpPVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFExPTR2Mj:nQnNCVkeHUkyvZV4>
SNU-387 M3Xyemdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYjJR|UxRTF7LkG4PFkh|ryP MUG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNFU1PDJxJ{7TRW5ITVJ:L3G+
ETK-1 MXrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYTXfIVqUUN3ME2xPU4yQDJ5IN88US=> M363cVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFExPTR2Mj:nQnNCVkeHUkyvZV4>
HuO9 NHGy[FVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGPU[HhKSzVyPUG5MlE{PzlizszN MY[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNFU1PDJxJ{7TRW5ITVJ:L3G+
RO82-W-1 NImzVHdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MoK5TWM2OD1zOD64Nlg5KM7:TR?= NUO1cYtORGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTB3NESyM{c,W0GQR1XSQE9iRg>?
D-502MG Mk\6S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2P4eWlEPTB;MUiuPFE{QSEQvF2= MV68ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNFU1PDJxJ{7TRW5ITVJ:L3G+
LS-123 MVHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4CydWlEPTB;MUiuO|kxOSEQvF2= NWHjRms1RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTB3NESyM{c,W0GQR1XSQE9iRg>?
OC-314 NIDYPVVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4jGd2lEPTB;MUiuO|M5PCEQvF2= NXfoR49LRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTB3NESyM{c,W0GQR1XSQE9iRg>?
Ramos-2G6-4C10 NXXLUXNFT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3\1SGlEPTB;MUiuOVkzPyEQvF2= MlXOQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVA2PDR{Lze+V2FPT0WUPD;hQi=>
SW962 M37DTGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYrVS2JMUUN3ME2xPE42PzB{IN88US=> NX3ZU2E4RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTB3NESyM{c,W0GQR1XSQE9iRg>?
SW982 MVXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVrJR|UxRTF6LkW2OFkh|ryP MlfOQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVA2PDR{Lze+V2FPT0WUPD;hQi=>
KYSE-410 MorSS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVi1[WVCUUN3ME2xPE41PTd5IN88US=> NF3jOWk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyODV2NEKvK|5USU6JRWK8M4E,
HT-3 NYTRUlMzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnvJTWM2OD1zOD6zPVc4KM7:TR?= M{W5d|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFExPTR2Mj:nQnNCVkeHUkyvZV4>
CAL-85-1 M13R[mdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIXBZo9KSzVyPUG4MlE5ODlizszN NWLNXYl1RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTB3NESyM{c,W0GQR1XSQE9iRg>?
BB30-HNC MlK2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3zvNmlEPTB;MUiuNFMyQCEQvF2= MYC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNFU1PDJxJ{7TRW5ITVJ:L3G+
D-247MG M{D4ZWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmjFTWM2OD1zNz65NlQ4KM7:TR?= MXW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNFU1PDJxJ{7TRW5ITVJ:L3G+
SCC-15 M1zsfmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEm1TIRKSzVyPUG3Mlg1PzNizszN M37tVlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFExPTR2Mj:nQnNCVkeHUkyvZV4>
BB49-HNC NV7LSW1QT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4PQ[WlEPTB;MUeuOVY5PiEQvF2= NWnmclJmRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTB3NESyM{c,W0GQR1XSQE9iRg>?
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CAL-39 MYfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4e5dWlEPTB;Mj64PVk6QSEQvF2= NXLSd2FvRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTB3NESyM{c,W0GQR1XSQE9iRg>?
LB2241-RCC MWfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHvuZ5JKSzVyPUKuPFU5QTNizszN NFmx[Xo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyODV2NEKvK|5USU6JRWK8M4E,
COLO-792 MUnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M373OWlEPTB;Mj64OFAzPyEQvF2= NWPJd3o4RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTB3NESyM{c,W0GQR1XSQE9iRg>?
HCE-T NHfINWVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M33PdmlEPTB;Mj64N|I3PCEQvF2= M4fzeVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFExPTR2Mj:nQnNCVkeHUkyvZV4>
BFTC-905 MVfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{fqN2lEPTB;Mj64NlU{KM7:TR?= NEi3cG89[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyODV2NEKvK|5USU6JRWK8M4E,
CHL-1 NHzo[Y1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NILIWI1KSzVyPUKuPFA4QDVizszN M1vuOVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFExPTR2Mj:nQnNCVkeHUkyvZV4>
L-363 NEDr[WJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MV\JR|UxRTJwN{SzO{DPxE1? NUPN[YVkRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTB3NESyM{c,W0GQR1XSQE9iRg>?
HCC2218 MW\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3Tnc2lEPTB;Mj62OFc4QCEQvF2= NIi5OFc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyODV2NEKvK|5USU6JRWK8M4E,
DB NYXTUYo4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NH75RY1KSzVyPUKuOVg4QDhizszN MXS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNFU1PDJxJ{7TRW5ITVJ:L3G+
EW-13 NX3YdJV5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXTMXWc1UUN3ME2yMlU3OzN7IN88US=> NYXaXJZuRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTB3NESyM{c,W0GQR1XSQE9iRg>?
KNS-62 NIX1TnZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnS0TWM2OD1{LkWxNVY1KM7:TR?= NVTHOpFPRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTB3NESyM{c,W0GQR1XSQE9iRg>?
RD NWTz[ldjT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnjiTWM2OD1{LkS0O|I{KM7:TR?= Mk[2QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVA2PDR{Lze+V2FPT0WUPD;hQi=>
BB65-RCC MnHPS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmDJTWM2OD1{LkSwOlc1KM7:TR?= NInzdZo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyODV2NEKvK|5USU6JRWK8M4E,
CAL-27 NHG5PGpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NY\ZbWJCUUN3ME2yMlM6OjN4IN88US=> MUS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNFU1PDJxJ{7TRW5ITVJ:L3G+
DOK M{nwfmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MknaTWM2OD1{LkO1O|c{KM7:TR?= NGexZY89[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyODV2NEKvK|5USU6JRWK8M4E,
NB7 Mn60S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MluxTWM2OD1{LkO0NFg3KM7:TR?= NGjMbXM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyODV2NEKvK|5USU6JRWK8M4E,
A2058 M1z0RWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Ml\oTWM2OD1{LkG5Nlc6KM7:TR?= NGLpR2c9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyODV2NEKvK|5USU6JRWK8M4E,
HN M2rsOWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEXyUW9KSzVyPUKuNVYzPzhizszN NInaN3o9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyODV2NEKvK|5USU6JRWK8M4E,
MZ2-MEL Ml3IS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NH\GbIVKSzVyPUKuNVEyOjdizszN MlqxQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVA2PDR{Lze+V2FPT0WUPD;hQi=>
EM-2 MYjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mnf2TWM2OD1{LkC3NVk5KM7:TR?= M1PjXVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFExPTR2Mj:nQnNCVkeHUkyvZV4>
HCC70 MlHpS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWe1dZY{UUN3ME2yMlAzPDJ4IN88US=> NWe4ZW1bRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTB3NESyM{c,W0GQR1XSQE9iRg>?
RXF393 MVzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXjJR|UxRTFwOUe4PFch|ryP NVXmcYoyRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTB3NESyM{c,W0GQR1XSQE9iRg>?
LCLC-97TM1 M1zJNWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFqwS4pKSzVyPUGuPVIzPTZizszN NVnJPHI5RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTB3NESyM{c,W0GQR1XSQE9iRg>?
A375 MXvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{X1S2lEPTB;MT64PVcyPCEQvF2= MX:8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNFU1PDJxJ{7TRW5ITVJ:L3G+
BPH-1 MULHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYjJR|UxRTFwOEm1PVEh|ryP MUS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNFU1PDJxJ{7TRW5ITVJ:L3G+
LOXIMVI NGT4U|JIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NV;ndm9qUUN3ME2xMlg6PDJ5IN88US=> M1e4XVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFExPTR2Mj:nQnNCVkeHUkyvZV4>
NCI-H292 NXuxSo8{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVi4enZ3UUN3ME2xMlg3Pjl7IN88US=> NYq4XldmRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTB3NESyM{c,W0GQR1XSQE9iRg>?
NB69 M3jJ[2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MkDWTWM2OD1zLke4OFY6KM7:TR?= MUe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNFU1PDJxJ{7TRW5ITVJ:L3G+
OVCAR-5 NV;yXHg4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHXCOJNKSzVyPUGuO|c3QDdizszN NEHHZ5k9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyODV2NEKvK|5USU6JRWK8M4E,
COLO-829 NGrsbndIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFLrVYpKSzVyPUGuOlIzOzJizszN NGLte2s9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyODV2NEKvK|5USU6JRWK8M4E,
RT-112 M2T1fWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2fsV2lEPTB;MT61PFk2OiEQvF2= M2fsU|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFExPTR2Mj:nQnNCVkeHUkyvZV4>
SK-MEL-2 NFuzV2xIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3TBTWlEPTB;MT61O|Q2QSEQvF2= M1vUXFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFExPTR2Mj:nQnNCVkeHUkyvZV4>
HD-MY-Z MlzlS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUi4b2tjUUN3ME2xMlU4Ozd4IN88US=> MXy8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNFU1PDJxJ{7TRW5ITVJ:L3G+
A4-Fuk M3i1Xmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1rhS2lEPTB;MT61O|A1PSEQvF2= MVu8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNFU1PDJxJ{7TRW5ITVJ:L3G+
SW1116 NWOxNVhPT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGPiSIhKSzVyPUGuOVY{QThizszN NG\vTGg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyODV2NEKvK|5USU6JRWK8M4E,
NCI-H1437 MkXOS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYDCXm9YUUN3ME2xMlU2Ojd3IN88US=> M{KycVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFExPTR2Mj:nQnNCVkeHUkyvZV4>
ML-2 M1\DcWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2q0bGlEPTB;MT61Nlg3QCEQvF2= NXzyeG5XRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTB3NESyM{c,W0GQR1XSQE9iRg>?
HO-1-N-1 MU\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mnn0TWM2OD1zLkWxOlM1KM7:TR?= NGe0WWw9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyODV2NEKvK|5USU6JRWK8M4E,
LoVo MoXFS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVTte5JzUUN3ME2xMlQ3Ozl7IN88US=> NH7L[5c9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyODV2NEKvK|5USU6JRWK8M4E,
LS-513 MnPQS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MoL5TWM2OD1zLkS1NVkzKM7:TR?= Ml;SQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVA2PDR{Lze+V2FPT0WUPD;hQi=>
BV-173 M4jsfmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2mxR2lEPTB;MT60OFAyPSEQvF2= MVm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNFU1PDJxJ{7TRW5ITVJ:L3G+
LS-411N NUL0NWxoT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnXxTWM2OD1zLkSwOVE4KM7:TR?= M17yWlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFExPTR2Mj:nQnNCVkeHUkyvZV4>
SW1463 M1HKNWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MV;JR|UxRTFwM{O3NlEh|ryP NXW4R3BLRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTB3NESyM{c,W0GQR1XSQE9iRg>?
NCI-H2291 NUXIN2NRT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXrTdGp4UUN3ME2xMlMzPTN4IN88US=> NHju[5I9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyODV2NEKvK|5USU6JRWK8M4E,
H-EMC-SS NGLNZ3BIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NF7TXYNKSzVyPUGuNlk3ODhizszN MkC3QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVA2PDR{Lze+V2FPT0WUPD;hQi=>
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NB1643 NWnGPVFjeUiWUzDhd5NigQ>? NFKwVI1yUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiTlKxOlQ{KGOnbHzz Mkj6QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN|koRjJ7NEO1NVM6RC:jPh?=
LAN-5 NWLUVVdbeUiWUzDhd5NigQ>? NX;VW|BVeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC|Y4Ll[Y4h\m:{IFzBUk02KGOnbHzz M{D6dlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
BT-12 Mn[3dWhVWyCjc4PhfS=> M{HyVpFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCEVD2xNkBk\Wyucx?= M3jQR|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
OHS-50 MmTndWhVWyCjc4PhfS=> MWXxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW|IH\vdkBlenWpIILldJVzeG:|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhV0iVLUWwJINmdGy| Ml;VQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN|koRjJ7NEO1NVM6RC:jPh?=
RD MUfxTHRUKGG|c3H5 NWS1dXdjeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC|Y4Ll[Y4h\m:{IGLEJINmdGy| NXXs[IZERGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N|UyOzlpPkK5OFM2OTN7PD;hQi=>
MG 63 (6-TG R) NFfJeWhyUFSVIHHzd4F6 Mmi1dWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[|ohWHKrbXHyfUB{[3KnZX6g[o9zKE2JIE[zJEg3NVSJIGKpJINmdGy| NF3QUo89[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N|UyOzl:L3G+
786-0 NWi2b5NPTnWwY4Tpc44h[XO|YYm= NFm5Z3YzPCCqcoO= NWnMcZc{UW6qaXLpeIlwdiCxZjDDT|IhcW5iaIXtZY4hPzh4LUCgZ4VtdHNiYYPz[ZN{\WRiYYOg[IVkemWjc3WgbY4hSWu2MTDwbI9{eGixconsZZRqd25iYYSgV4VzOTJ7IHHmeIVzKDJ2IHjyd{BjgSCZZYP0[ZJvKGKub4SgZY5idHm|aYOsJGVEPTB;MD6x{txO MVW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8{ODZ6OUm0Okc,OzB4OEm5OFY9N2F-
Assay
Methods Test Index PMID
Western blot p-ERK1/2 / ERK1/2 ; p-ERK5 / ERK5 21762482
Growth inhibition assay Cell viability 29989268
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]

Protocol (from 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 Research:

[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 Research:

[3]

  • Animal Models: PTC cells in athymic mice
  • Dosages: 150 mg/kg
  • Administration: Orally twice daily

Solubility (25°C)

In vitro

In vivo

Add solvents to the product individually and in order
(Data is from Selleck tests instead of citations):
30% PEG400+0.5% Tween80+5% propylene glycol, pH 9
For best results, use promptly after mixing.

10 mg/mL

Chemical Information

Molecular Weight 478.67
Formula

C17H14ClF2IN2O2

CAS No. 212631-79-3
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles C1CC1CONC(=O)C2=C(C(=C(C=C2)F)F)NC3=C(C=C(C=C3)I)Cl

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg g μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Molarity Calculator

Mass Concentration Volume Molecular Weight

Tech Support

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.

Handling Instructions

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