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 MlHZS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NIXn[2JKSzVyPUK0MlA2OjZizszN MVK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNFU1PDJxJ{7TRW5ITVJ:L3G+
VM-CUB-1 NYn4WYtoT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mn[zTWM2OD1{Mz63N|QyKM7:TR?= NWH5N3V6RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTB3NESyM{c,W0GQR1XSQE9iRg>?
LC-2-ad NHHiR3pIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWPtfJVoUUN3ME2yN{43OTR5IN88US=> M4\TclxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFExPTR2Mj:nQnNCVkeHUkyvZV4>
A704 NEHuRmhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWDVe4g2UUN3ME2yN{43OTB|IN88US=> MnqwQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVA2PDR{Lze+V2FPT0WUPD;hQi=>
DMS-114 M1;ue2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGTGWGRKSzVyPUKzMlU4PjVizszN MoPDQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVA2PDR{Lze+V2FPT0WUPD;hQi=>
EKVX NE\UWGxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MU\JR|UxRTJ|LkO5NFkh|ryP NILyeGo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyODV2NEKvK|5USU6JRWK8M4E,
SNU-449 MVzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXfJR|UxRTJ|LkOyPUDPxE1? NFzzcJQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyODV2NEKvK|5USU6JRWK8M4E,
HCC1806 NVvqeotJT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NEHnSYZKSzVyPUKzMlA2QDNizszN MWi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNFU1PDJxJ{7TRW5ITVJ:L3G+
CaR-1 MYnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWLUcHVmUUN3ME2yN{4xOjF|IN88US=> MXO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNFU1PDJxJ{7TRW5ITVJ:L3G+
NCI-H441 M{TqW2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NInORZlKSzVyPUKyMlU3QDlizszN M{T3OlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFExPTR2Mj:nQnNCVkeHUkyvZV4>
TI-73 NFy0dFRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Ml:yTWM2OD1{Mj6zNlgh|ryP MYq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNFU1PDJxJ{7TRW5ITVJ:L3G+
NCI-H1755 MUDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2[zc2lEPTB;MkGuOlc1OSEQvF2= M2XHXFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFExPTR2Mj:nQnNCVkeHUkyvZV4>
A498 MlraS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGi3eFVKSzVyPUKxMlU{OTJizszN M3PLTFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFExPTR2Mj:nQnNCVkeHUkyvZV4>
CFPAC-1 NYnSR|ltT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGPSTpRKSzVyPUKxMlM5PThizszN NFvWXIQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyODV2NEKvK|5USU6JRWK8M4E,
ChaGo-K-1 NHTlWo9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2HPfGlEPTB;MkGuN|YzPyEQvF2= M3Hye|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFExPTR2Mj:nQnNCVkeHUkyvZV4>
KP-4 NYDFSVZyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mk\hTWM2OD1{MT6xNVk3KM7:TR?= NIHCe|E9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyODV2NEKvK|5USU6JRWK8M4E,
Becker M3fBOGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NU\1bFlNUUN3ME2yNU4yOTF6IN88US=> NGO1TIs9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyODV2NEKvK|5USU6JRWK8M4E,
UMC-11 M4LuU2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYPJR|UxRTJyLkmxOlQh|ryP M3\F[FxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFExPTR2Mj:nQnNCVkeHUkyvZV4>
TE-6 MlnzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnSyTWM2OD1{MD64NFY4KM7:TR?= MXO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNFU1PDJxJ{7TRW5ITVJ:L3G+
SF539 M1KyZ2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlfwTWM2OD1{MD61NVczKM7:TR?= MWi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNFU1PDJxJ{7TRW5ITVJ:L3G+
FTC-133 M4Tsbmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4\5dGlEPTB;MkCuOFcxOyEQvF2= MXu8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNFU1PDJxJ{7TRW5ITVJ:L3G+
NCI-H226 NV[zTVJkT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MV7JR|UxRTJyLkSzPVkh|ryP MX[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNFU1PDJxJ{7TRW5ITVJ:L3G+
NCI-H1048 MnLQS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGD3WIZKSzVyPUKwMlMzPjZizszN MXO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNFU1PDJxJ{7TRW5ITVJ:L3G+
Calu-3 M{j1S2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{HiemlEPTB;MUmuOFI{PyEQvF2= NUHWVmJiRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTB3NESyM{c,W0GQR1XSQE9iRg>?
SF126 M33QdGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mmr3TWM2OD1zOT6zOVAzKM7:TR?= MU[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNFU1PDJxJ{7TRW5ITVJ:L3G+
NTERA-S-cl-D1 M{jmdmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2rUeGlEPTB;MUmuNlAxPyEQvF2= MlTTQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVA2PDR{Lze+V2FPT0WUPD;hQi=>
SW1573 MkfNS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1\4R2lEPTB;MUmuNVk3QSEQvF2= NWjWV3dyRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTB3NESyM{c,W0GQR1XSQE9iRg>?
SNU-387 MWnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXPJR|UxRTF7LkG4PFkh|ryP MX28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNFU1PDJxJ{7TRW5ITVJ:L3G+
ETK-1 MkfPS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVvJR|UxRTF7LkG4Nlch|ryP Mm\MQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVA2PDR{Lze+V2FPT0WUPD;hQi=>
HuO9 NV7QOWZ1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXnOTINsUUN3ME2xPU4yOzd7IN88US=> NHLwcFU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyODV2NEKvK|5USU6JRWK8M4E,
RO82-W-1 MVzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MofhTWM2OD1zOD64Nlg5KM7:TR?= M3GxSFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFExPTR2Mj:nQnNCVkeHUkyvZV4>
D-502MG MWDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHO2c2ZKSzVyPUG4MlgyOzlizszN NWTRSnV5RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTB3NESyM{c,W0GQR1XSQE9iRg>?
LS-123 MV7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYHJR|UxRTF6Lke5NFEh|ryP NUi3cGVvRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTB3NESyM{c,W0GQR1XSQE9iRg>?
OC-314 NH;TTFVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NULibIZJUUN3ME2xPE44Ozh2IN88US=> NIS0N|A9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyODV2NEKvK|5USU6JRWK8M4E,
Ramos-2G6-4C10 M1vJVWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1\iVmlEPTB;MUiuOVkzPyEQvF2= MWS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNFU1PDJxJ{7TRW5ITVJ:L3G+
SW962 NFXrZ4dIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXTMW4JQUUN3ME2xPE42PzB{IN88US=> NFyzOG89[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyODV2NEKvK|5USU6JRWK8M4E,
SW982 NYDlSYxRT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWjjNIx{UUN3ME2xPE42PjR7IN88US=> NYSzNolbRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTB3NESyM{c,W0GQR1XSQE9iRg>?
KYSE-410 NGmw[pFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXnuUZR[UUN3ME2xPE41PTd5IN88US=> MmTJQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVA2PDR{Lze+V2FPT0WUPD;hQi=>
HT-3 M3WwWWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFnyd2hKSzVyPUG4MlM6PzdizszN NV7CV4R7RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTB3NESyM{c,W0GQR1XSQE9iRg>?
CAL-85-1 M33wOGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlvMTWM2OD1zOD6xPFA6KM7:TR?= NFflVVM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyODV2NEKvK|5USU6JRWK8M4E,
BB30-HNC MX;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mn3PTWM2OD1zOD6wN|E5KM7:TR?= MV[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNFU1PDJxJ{7TRW5ITVJ:L3G+
D-247MG MUnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NE[xTHJKSzVyPUG3MlkzPDdizszN MlHqQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVA2PDR{Lze+V2FPT0WUPD;hQi=>
SCC-15 MnLjS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3XLfWlEPTB;MUeuPFQ4OyEQvF2= NGnnWmI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyODV2NEKvK|5USU6JRWK8M4E,
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KYSE-70 NHnKOHJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWXJR|UxRTF5LkK4PUDPxE1? M1P6UVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFExPTR2Mj:nQnNCVkeHUkyvZV4>
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LB831-BLC NVPKT4NKT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGPlW|RKSzVyPUG0Mlg6OzRizszN MoTJQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVA2PDR{Lze+V2FPT0WUPD;hQi=>
BT-549 NUfjSZoyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3G2U2lEPTB;MUSuPFI5PCEQvF2= NGHpcoE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyODV2NEKvK|5USU6JRWK8M4E,
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BALL-1 NWLQW5J3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGTRdJFKSzVyPUG0MlQ3PjVizszN NIfCNYw9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyODV2NEKvK|5USU6JRWK8M4E,
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GCT NVzZO|h7T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUnhbph7UUN3ME2xN{46Pjl5IN88US=> MnTlQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVA2PDR{Lze+V2FPT0WUPD;hQi=>
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SF268 NVrTNFg4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NU\mXXdWUUN3ME2xN{43OzJ4IN88US=> MmrjQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVA2PDR{Lze+V2FPT0WUPD;hQi=>
NCI-H2009 Ml7yS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2[5PGlEPTB;MUOuOVkyQSEQvF2= MXW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNFU1PDJxJ{7TRW5ITVJ:L3G+
CAPAN-1 NIn4Z5RIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmnWTWM2OD1zMz61OVE1KM7:TR?= MWe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNFU1PDJxJ{7TRW5ITVJ:L3G+
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NCI-H727 NH\MeohIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGPp[4ZKSzVyPUKuPVE4QTZizszN NEXKR409[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyODV2NEKvK|5USU6JRWK8M4E,
T-24 NHywSlVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NX72eIJxUUN3ME2yMlkyOTF{IN88US=> NHm2W5A9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyODV2NEKvK|5USU6JRWK8M4E,
CAL-39 MoTiS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXWyOIs2UUN3ME2yMlg6QTl7IN88US=> MkHpQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVA2PDR{Lze+V2FPT0WUPD;hQi=>
LB2241-RCC NW\v[GVRT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXXhVIw2UUN3ME2yMlg2QDl|IN88US=> NW\JdHlvRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTB3NESyM{c,W0GQR1XSQE9iRg>?
COLO-792 Mlj4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVLBW|FXUUN3ME2yMlg1ODJ5IN88US=> MWe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNFU1PDJxJ{7TRW5ITVJ:L3G+
HCE-T M3PSSWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NW\tVmh4UUN3ME2yMlg{OjZ2IN88US=> M3fHNlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFExPTR2Mj:nQnNCVkeHUkyvZV4>
BFTC-905 NGGzeJFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVT2WWExUUN3ME2yMlgzPTNizszN MknKQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVA2PDR{Lze+V2FPT0WUPD;hQi=>
CHL-1 NGrW[IRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGrqe4lKSzVyPUKuPFA4QDVizszN MnfTQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVA2PDR{Lze+V2FPT0WUPD;hQi=>
L-363 MnHjS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVzJR|UxRTJwN{SzO{DPxE1? MYW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNFU1PDJxJ{7TRW5ITVJ:L3G+
HCC2218 NWTIV4p2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVPYVnFYUUN3ME2yMlY1Pzd6IN88US=> MUi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNFU1PDJxJ{7TRW5ITVJ:L3G+
DB M{CzWmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2XsTWlEPTB;Mj61PFc5QCEQvF2= NWj0T4xCRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTB3NESyM{c,W0GQR1XSQE9iRg>?
EW-13 MWLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVjJR|UxRTJwNU[zN|kh|ryP M{\idlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFExPTR2Mj:nQnNCVkeHUkyvZV4>
KNS-62 NVT5[WZbT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NEjHUopKSzVyPUKuOVEyPjRizszN MYG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNFU1PDJxJ{7TRW5ITVJ:L3G+
RD NEDJ[FZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4e1fmlEPTB;Mj60OFczOyEQvF2= M4Hr[FxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFExPTR2Mj:nQnNCVkeHUkyvZV4>
BB65-RCC NFrpepJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1;3cGlEPTB;Mj60NFY4PCEQvF2= M{TwUFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFExPTR2Mj:nQnNCVkeHUkyvZV4>
CAL-27 MYLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NH;3XpFKSzVyPUKuN|kzOzZizszN MoHqQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVA2PDR{Lze+V2FPT0WUPD;hQi=>
DOK NUf6W5d1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWTJR|UxRTJwM{W3O|Mh|ryP NILvT|A9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyODV2NEKvK|5USU6JRWK8M4E,
NB7 MV3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlmyTWM2OD1{LkO0NFg3KM7:TR?= MVi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNFU1PDJxJ{7TRW5ITVJ:L3G+
A2058 MoOxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWewVYlZUUN3ME2yMlE6Ojd7IN88US=> MWK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNFU1PDJxJ{7TRW5ITVJ:L3G+
HN MW\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYLJR|UxRTJwMU[yO|gh|ryP M1jiO|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFExPTR2Mj:nQnNCVkeHUkyvZV4>
MZ2-MEL MmjoS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MoW5TWM2OD1{LkGxNVI4KM7:TR?= NXO4SIRWRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTB3NESyM{c,W0GQR1XSQE9iRg>?
EM-2 MYjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MV\JR|UxRTJwMEexPVgh|ryP M4Had|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFExPTR2Mj:nQnNCVkeHUkyvZV4>
HCC70 MXvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlPwTWM2OD1{LkCyOFI3KM7:TR?= M4LDSFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFExPTR2Mj:nQnNCVkeHUkyvZV4>
RXF393 NF\IWHZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkXUTWM2OD1zLkm3PFg4KM7:TR?= MYq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNFU1PDJxJ{7TRW5ITVJ:L3G+
LCLC-97TM1 M4DUTmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MkTFTWM2OD1zLkmyNlU3KM7:TR?= NYXPRYE5RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTB3NESyM{c,W0GQR1XSQE9iRg>?
A375 MYPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1PSfmlEPTB;MT64PVcyPCEQvF2= MXe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNFU1PDJxJ{7TRW5ITVJ:L3G+
BPH-1 MYfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mk[4TWM2OD1zLki5OVkyKM7:TR?= NGrRU2U9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyODV2NEKvK|5USU6JRWK8M4E,
LOXIMVI NYPEbIl{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MmXMTWM2OD1zLki5OFI4KM7:TR?= MmXQQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVA2PDR{Lze+V2FPT0WUPD;hQi=>
NCI-H292 NYrzc5FWT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXTJR|UxRTFwOE[2PVkh|ryP MmrWQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVA2PDR{Lze+V2FPT0WUPD;hQi=>
NB69 NFn1bJdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUe1OmppUUN3ME2xMlc5PDZ7IN88US=> NGLIToo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyODV2NEKvK|5USU6JRWK8M4E,
OVCAR-5 MoLpS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWDJR|UxRTFwN{e2PFch|ryP MXe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNFU1PDJxJ{7TRW5ITVJ:L3G+
COLO-829 MWXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmrDTWM2OD1zLk[yNlMzKM7:TR?= M1LD[|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFExPTR2Mj:nQnNCVkeHUkyvZV4>
RT-112 M{PwUWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{jhT2lEPTB;MT61PFk2OiEQvF2= MU[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNFU1PDJxJ{7TRW5ITVJ:L3G+
SK-MEL-2 NGnPcndIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mo\1TWM2OD1zLkW3OFU6KM7:TR?= M2XUNFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFExPTR2Mj:nQnNCVkeHUkyvZV4>
HD-MY-Z NHrrRZlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXy2T3NbUUN3ME2xMlU4Ozd4IN88US=> NFvxN449[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyODV2NEKvK|5USU6JRWK8M4E,
A4-Fuk M4jodmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MX3JR|UxRTFwNUewOFUh|ryP NX3PSXd{RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTB3NESyM{c,W0GQR1XSQE9iRg>?
SW1116 NIfhSFBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NV7EUJZCUUN3ME2xMlU3Ozl6IN88US=> M4Xq[|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFExPTR2Mj:nQnNCVkeHUkyvZV4>
NCI-H1437 MWPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXfJR|UxRTFwNUWyO|Uh|ryP NH[xfGM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyODV2NEKvK|5USU6JRWK8M4E,
ML-2 MXLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIXXRmVKSzVyPUGuOVI5PjhizszN M1XoXlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFExPTR2Mj:nQnNCVkeHUkyvZV4>
HO-1-N-1 NGnXemdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYjCOJdpUUN3ME2xMlUyPjN2IN88US=> M2\kdlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFExPTR2Mj:nQnNCVkeHUkyvZV4>
LoVo Mnz5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlnUTWM2OD1zLkS2N|k6KM7:TR?= MVy8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNFU1PDJxJ{7TRW5ITVJ:L3G+
LS-513 NV;IdFRnT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1TKXWlEPTB;MT60OVE6OiEQvF2= NGXzW4Y9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyODV2NEKvK|5USU6JRWK8M4E,
BV-173 MmHBS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVvJR|UxRTFwNESwNVUh|ryP NW\IRnc1RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTB3NESyM{c,W0GQR1XSQE9iRg>?
LS-411N NXPVT3RuT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MY\JR|UxRTFwNEC1NVch|ryP M1jnSVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFExPTR2Mj:nQnNCVkeHUkyvZV4>
SW1463 MW\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYPmb2VkUUN3ME2xMlM{PzJzIN88US=> NGCwVVA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyODV2NEKvK|5USU6JRWK8M4E,
NCI-H2291 MVLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2OxNmlEPTB;MT6zNlU{PiEQvF2= NWTLbpVyRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTB3NESyM{c,W0GQR1XSQE9iRg>?
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SK-N-MC MX7xTHRUKGG|c3H5 NW\rSZI{eUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC|Y4Ll[Y4h\m:{IGPLMW4uVUNiY3XscJM> NV20TlRjRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N|UyOzlpPkK5OFM2OTN7PD;hQi=>
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NB-EBc1 MXrxTHRUKGG|c3H5 NHPiXlFyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiTlKtSWJkOSClZXzsdy=> NFjKN3Q9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N|UyOzl:L3G+
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SK-N-SH MlGwdWhVWyCjc4PhfS=> NFLhZoVyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiU1utUk1UUCClZXzsdy=> NVPFOW05RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N|UyOzlpPkK5OFM2OTN7PD;hQi=>
NB1643 NIPzO3RyUFSVIHHzd4F6 NFfDSGpyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiTlKxOlQ{KGOnbHzz M2nlSFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
LAN-5 NEf1O2lyUFSVIHHzd4F6 MWfxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW|IH\vdkBlenWpIILldJVzeG:|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhVEGQLUWgZ4VtdHN? M2j1UFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
BT-12 MlTGdWhVWyCjc4PhfS=> NVi0Tm5seUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC|Y4Ll[Y4h\m:{IFLUMVEzKGOnbHzz M4PQ[lxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
OHS-50 M3yxU5FJXFNiYYPzZZk> MlfDdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[|ohWHKrbXHyfUB{[3KnZX6g[o9zKE:KUz21NEBk\Wyucx?= NILMOWw9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N|UyOzl:L3G+
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MG 63 (6-TG R) MYfxTHRUKGG|c3H5 M4DOV5FJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCPRzC2N{ApPi2WRzDSLUBk\Wyucx?= M4\pOFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
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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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