Bosutinib (SKI-606)

Licensed by Pfizer Catalog No.S1014

For research use only.

Bosutinib (SKI-606) is a novel, dual Src/Abl inhibitor with IC50 of 1.2 nM and 1 nM in cell-free assays, respectively. Bosutinib also effectively decreases the activity of PI3K/AKT/mTOR, MAPK/ERK and JAK/STAT3 signaling pathways by blocking the phosphorylation levels of p-ERK, p-S6, and p-STAT3. Bosutinib promotes autophagy.

Bosutinib (SKI-606) Chemical Structure

CAS No. 380843-75-4

Selleck's Bosutinib (SKI-606) has been cited by 103 publications

Purity & Quality Control

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Biological Activity

Description Bosutinib (SKI-606) is a novel, dual Src/Abl inhibitor with IC50 of 1.2 nM and 1 nM in cell-free assays, respectively. Bosutinib also effectively decreases the activity of PI3K/AKT/mTOR, MAPK/ERK and JAK/STAT3 signaling pathways by blocking the phosphorylation levels of p-ERK, p-S6, and p-STAT3. Bosutinib promotes autophagy.
Targets
S6 kinase [7]
()
ERK [7]
()
STAT3 [7]
()
Abl [2]
(Cell-free assay)
Src [1]
(Cell-free assay)
1 nM 1.2 nM
In vitro

Bosutinib is selective for Src over non-Src family kinases with an IC50 of 1.2 nM, and potently inhibits Src-dependent cell proliferation with an IC50 of 100 nM. [1] Bosutinib significantly inhibits the proliferation of Bcr-Abl-positive leukemia cell lines KU812, K562, and MEG-01 but not Molt-4, HL-60, Ramos, and other leukemia cell lines, with IC50 of 5 nM, 20 nM and 20 nM, respectively, more potently than that of STI-571. Similar to STI-571, Bosutinib displays antiproliferative activity against the Abl-MLV-transformed fibroblasts with IC50 of 90 nM. Bosutinib ablates tyrosine phosphorylation of Bcr-Abl and STAT5 in CML cells and of v-Abl expressed in fibroblasts at the concentration of ~50 nM, 10-25 nM and 200 nM, respectively, leading to the Bcr-Abl downstream signaling inhibition of Lyn/Hck phosphorylation. [2] Although unable to inhibit the proliferation and survival of breast cancer cells, Bosutinib significantly decreases the motility and invasion of breast cancer cells with IC50 of ~250 nM, involved with an increase in cell-to-cell adhesion and membrane localization of β-catenin. [3]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
NB7 MWrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkH4TWM2OD1yLkC4NlMyKCEQvF2= NIHJRpI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwzQDh2NEGvK|5USU6JRWK8M4E,
SW756 MlT5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1nWZ2lEPTB;MD6xOFAzPCBizszN M1LwO|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFI5QDR2MT:nQnNCVkeHUkyvZV4>
CTV-1 MoPNS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2DPVmlEPTB;MD6xOlM6QCBizszN MYO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyyPFg1PDFxJ{7TRW5ITVJ:L3G+
HSC-4 NVf3b21vT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MkK3TWM2OD1yLkG3NVU5KCEQvF2= MX68ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyyPFg1PDFxJ{7TRW5ITVJ:L3G+
LAMA-84 MkH3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2XORmlEPTB;MD6yPFY3PCBizszN MYe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyyPFg1PDFxJ{7TRW5ITVJ:L3G+
KU812 M1X1RWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYHC[XNRUUN3ME2wMlM1ODZ6IDFOwG0> MkGxQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNlg5PDRzLze+V2FPT0WUPD;hQi=>
HCC1806 MVLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVH1RZZqUUN3ME2wMlM2OjF4IDFOwG0> Mnu3QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNlg5PDRzLze+V2FPT0WUPD;hQi=>
DOK M2Dhfmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mn7qTWM2OD1yLkO3O|g3KCEQvF2= MnGyQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNlg5PDRzLze+V2FPT0WUPD;hQi=>
NCI-H209 M37ITGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MorGTWM2OD1yLkSwPFA5KCEQvF2= NELrc4Q9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwzQDh2NEGvK|5USU6JRWK8M4E,
EoL-1-cell NY\qVIxtT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVzJR|UxRTBwNEG1O|YhKM7:TR?= Mln4QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNlg5PDRzLze+V2FPT0WUPD;hQi=>
H9 NGnENGNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NInTTIhKSzVyPUCuOFM1PjRiIN88US=> NUfGbopzRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOjh6NESxM{c,W0GQR1XSQE9iRg>?
EM-2 NYThcHI5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mk\1TWM2OD1yLkSzPFkhKM7:TR?= MUW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyyPFg1PDFxJ{7TRW5ITVJ:L3G+
NCI-H292 NFPvbVhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYHJR|UxRTBwNESxNFghKM7:TR?= M4Hab|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFI5QDR2MT:nQnNCVkeHUkyvZV4>
697 Mo[5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2O3ZWlEPTB;MD60OVY{OyBizszN NGf6O|c9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwzQDh2NEGvK|5USU6JRWK8M4E,
BHT-101 MUnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NV;YXIE3UUN3ME2wMlQ3PTliIN88US=> MXK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyyPFg1PDFxJ{7TRW5ITVJ:L3G+
BE-13 M4O1emdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2XLO2lEPTB;MD60PFU4OiBizszN NV7rcopGRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOjh6NESxM{c,W0GQR1XSQE9iRg>?
RS4-11 MXHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mk\KTWM2OD1yLkS4OVg1KCEQvF2= M33rUVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFI5QDR2MT:nQnNCVkeHUkyvZV4>
IGROV-1 M4WwUmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWSyNFdrUUN3ME2wMlQ5Pzl5IDFOwG0> MV:8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyyPFg1PDFxJ{7TRW5ITVJ:L3G+
KE-37 M2XIdmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYPJR|UxRTBwNEm1NFkhKM7:TR?= M1nLVlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFI5QDR2MT:nQnNCVkeHUkyvZV4>
BV-173 NEfqWXNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVqwXY92UUN3ME2wMlUxPzl{IDFOwG0> M1fBfFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFI5QDR2MT:nQnNCVkeHUkyvZV4>
MEG-01 NYLZNlk3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUnJR|UxRTBwNUGyNVQhKM7:TR?= NXL0bVQzRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOjh6NESxM{c,W0GQR1XSQE9iRg>?
LB2241-RCC MoXNS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mny4TWM2OD1yLkWzO|E5KCEQvF2= MWi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyyPFg1PDFxJ{7TRW5ITVJ:L3G+
ACHN MVnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWPGVYJZUUN3ME2wMlU1ODZ7IDFOwG0> NYnzem1PRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOjh6NESxM{c,W0GQR1XSQE9iRg>?
CTB-1 NUPkS5VOT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXv6NJBjUUN3ME2wMlU1QDJiIN88US=> M2nycFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFI5QDR2MT:nQnNCVkeHUkyvZV4>
HT-1080 M2HRNWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYHsSI9bUUN3ME2wMlU2OzR7IDFOwG0> M4LH[lxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFI5QDR2MT:nQnNCVkeHUkyvZV4>
CHL-1 MmDJS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEHPfWpKSzVyPUCuOVU1PjViIN88US=> M17JXlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFI5QDR2MT:nQnNCVkeHUkyvZV4>
EW-3 NIXXUFFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIjxdFZKSzVyPUCuOVU6OzViIN88US=> M3HVZVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFI5QDR2MT:nQnNCVkeHUkyvZV4>
ES1 MVPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2G2N2lEPTB;MD62O|Q6QCBizszN M2KxTlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFI5QDR2MT:nQnNCVkeHUkyvZV4>
KASUMI-1 NHfGcGJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUT6NZNEUUN3ME2wMlczOzNiIN88US=> M4C3RVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFI5QDR2MT:nQnNCVkeHUkyvZV4>
SW13 NHTDSXJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MX;JR|UxRTBwN{O3PVghKM7:TR?= NIrlN2U9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwzQDh2NEGvK|5USU6JRWK8M4E,
A3-KAW NYPNdWV[T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVTkb5dPUUN3ME2wMlc6OjB6IDFOwG0> M{nY[FxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFI5QDR2MT:nQnNCVkeHUkyvZV4>
LB771-HNC NXfydWp[T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXLFO|Z6UUN3ME2wMlg{OTB2IDFOwG0> M2W2b|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFI5QDR2MT:nQnNCVkeHUkyvZV4>
OC-314 NGWyOoxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmPZTWM2OD1yLki2PVY2KCEQvF2= MV28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyyPFg1PDFxJ{7TRW5ITVJ:L3G+
MLMA MUTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFfXVZJKSzVyPUCuPVA3PzViIN88US=> NHHaU|k9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwzQDh2NEGvK|5USU6JRWK8M4E,
KARPAS-45 MWPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYLJR|UxRTBwOUK0OlYhKM7:TR?= MnrQQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNlg5PDRzLze+V2FPT0WUPD;hQi=>
CAL-27 MXjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUftdJhyUUN3ME2wMlkzQTB4IDFOwG0> NVHsXHhsRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOjh6NESxM{c,W0GQR1XSQE9iRg>?
SK-NEP-1 NVjkfVRwT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVLGTGlXUUN3ME2wMlk4OjR6IDFOwG0> M1j1VlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFI5QDR2MT:nQnNCVkeHUkyvZV4>
COR-L105 NXjtcJpOT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NH;IW|FKSzVyPUGuNFA{QTRiIN88US=> NV7obotzRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOjh6NESxM{c,W0GQR1XSQE9iRg>?
TI-73 MmLxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEWyd4ZKSzVyPUGuNFE3PSBizszN MXO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyyPFg1PDFxJ{7TRW5ITVJ:L3G+
JVM-3 NIHxcVJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmHLTWM2OD1zLkC1NFE4KCEQvF2= M4XZblxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFI5QDR2MT:nQnNCVkeHUkyvZV4>
HAL-01 MYLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mo[2TWM2OD1zLkC4PFEhKM7:TR?= M1Pk[FxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFI5QDR2MT:nQnNCVkeHUkyvZV4>
QIMR-WIL MVHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYnJR|UxRTFwMEmwOVghKM7:TR?= M4TJeFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFI5QDR2MT:nQnNCVkeHUkyvZV4>
HSC-3 NGHCTFZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4PFZmlEPTB;MT6xNVc5OyBizszN NH3mbnY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwzQDh2NEGvK|5USU6JRWK8M4E,
KY821 NXvVfY5iT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHPFWHZKSzVyPUGuNVM{PTFiIN88US=> MoPDQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNlg5PDRzLze+V2FPT0WUPD;hQi=>
5637 MlPPS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Ml\ETWM2OD1zLkGzPFA{KCEQvF2= NVTQV3JmRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOjh6NESxM{c,W0GQR1XSQE9iRg>?
CAL-33 MV7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUH6Zox{UUN3ME2xMlE6OzB{IDFOwG0> M4DEb|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFI5QDR2MT:nQnNCVkeHUkyvZV4>
ES4 MorWS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGX2dXVKSzVyPUGuNlA4QSBizszN MoTZQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNlg5PDRzLze+V2FPT0WUPD;hQi=>
BHY M{WyUmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MW\JR|UxRTFwMkK4PVIhKM7:TR?= NHLje4Q9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwzQDh2NEGvK|5USU6JRWK8M4E,
LB1047-RCC NHjLN2FIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NV;BfHF1UUN3ME2xMlI{Pzh3IDFOwG0> MXK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyyPFg1PDFxJ{7TRW5ITVJ:L3G+
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RPMI-8866 M4O4bWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYDLS25xUUN3ME2xMlI3OTB4IDFOwG0> NXLaN2pTRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOjh6NESxM{c,W0GQR1XSQE9iRg>?
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PC-14 MXXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NG\YSXVKSzVyPUGuNlkzODViIN88US=> Mm\jQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNlg5PDRzLze+V2FPT0WUPD;hQi=>
NUGC-3 NEXwTGlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWf4TJpTUUN3ME2xMlI6OzV4IDFOwG0> M1rSdlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFI5QDR2MT:nQnNCVkeHUkyvZV4>
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MHH-NB-11 M{LPTmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVnadlNIUUN3ME2xMlMyOzh|IDFOwG0> NI\rSnc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwzQDh2NEGvK|5USU6JRWK8M4E,
KOSC-2 MYfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkPWTWM2OD1zLkOxO|c2KCEQvF2= NXP5bIFURGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOjh6NESxM{c,W0GQR1XSQE9iRg>?
A498 NHLwd45Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NX\EOldHUUN3ME2xMlQxOTF|IDFOwG0> MV28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyyPFg1PDFxJ{7TRW5ITVJ:L3G+
KG-1 NGr1eWVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVzyc4pWUUN3ME2xMlQyOjd|IDFOwG0> NXfLWoVXRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOjh6NESxM{c,W0GQR1XSQE9iRg>?
DEL NHzRelFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGn0WZRKSzVyPUGuOFM3PTdiIN88US=> M{fXSVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFI5QDR2MT:nQnNCVkeHUkyvZV4>
EW-16 MY\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkPXTWM2OD1zLkSzPVc{KCEQvF2= M1Xa[FxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFI5QDR2MT:nQnNCVkeHUkyvZV4>
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JAR NWj6OoZoT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MoK0TWM2OD1zLkS5N|YhKM7:TR?= MlPtQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNlg5PDRzLze+V2FPT0WUPD;hQi=>
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A375 NY[4PY5rT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnvsTWM2OD1zLkWxO|czKCEQvF2= MkDaQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNlg5PDRzLze+V2FPT0WUPD;hQi=>
SW954 M3PIb2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnW1TWM2OD1zLkW1NFA4KCEQvF2= MorvQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNlg5PDRzLze+V2FPT0WUPD;hQi=>
Ca9-22 NHvkOmdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYnLeYZCUUN3ME2xMlU3OjZiIN88US=> NXntRVBKRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOjh6NESxM{c,W0GQR1XSQE9iRg>?
D-566MG NEXTS|RIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVHJR|UxRTFwNUexOVUhKM7:TR?= NXHrTYlKRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOjh6NESxM{c,W0GQR1XSQE9iRg>?
SCC-15 NYriUHM6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NEfPcHdKSzVyPUGuOlE5ODRiIN88US=> MWS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyyPFg1PDFxJ{7TRW5ITVJ:L3G+
HD-MY-Z MYHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mn3vTWM2OD1zLk[zOVg1KCEQvF2= NXHUfYJ3RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOjh6NESxM{c,W0GQR1XSQE9iRg>?
HT-1376 M17Nemdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmS5TWM2OD1zLk[0N|YhKM7:TR?= NUXzcI16RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOjh6NESxM{c,W0GQR1XSQE9iRg>?
CAL-54 NESyTJhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWLJR|UxRTFwNkW3NFkhKM7:TR?= NEnnVpg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwzQDh2NEGvK|5USU6JRWK8M4E,
ONS-76 M1T1dGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVrJR|UxRTFwNke1OVEhKM7:TR?= M1\oTlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFI5QDR2MT:nQnNCVkeHUkyvZV4>
EFO-27 NXX5R4ZYT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWXJR|UxRTFwNki5NkAh|ryP MlrXQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNlg5PDRzLze+V2FPT0WUPD;hQi=>
769-P MX7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHm3d21KSzVyPUGuOlk2QTZiIN88US=> M{mz[lxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFI5QDR2MT:nQnNCVkeHUkyvZV4>
MV-4-11 Mnu1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVK1OJZ4UUN3ME2xMlY6QDV4IDFOwG0> NWnvdY9QRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOjh6NESxM{c,W0GQR1XSQE9iRg>?
NKM-1 NE[5OHpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mnj2TWM2OD1zLkexPFAzKCEQvF2= M4HRSlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFI5QDR2MT:nQnNCVkeHUkyvZV4>
LOXIMVI Ml70S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWHJR|UxRTFwN{S1PVkhKM7:TR?= MnTyQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNlg5PDRzLze+V2FPT0WUPD;hQi=>
KYSE-140 MYPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYPkSm5rUUN3ME2xMlc2PjV3IDFOwG0> NYOyNW84RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOjh6NESxM{c,W0GQR1XSQE9iRg>?
ES5 MWnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3u3dGlEPTB;MT64Olc1PyBizszN NXK5NZNyRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOjh6NESxM{c,W0GQR1XSQE9iRg>?
BB65-RCC NHPaSYpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlvVTWM2OD1zLki5PFQ6KCEQvF2= NVTrNWx{RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOjh6NESxM{c,W0GQR1XSQE9iRg>?
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A101D NFza[JBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYD2Z4JkUUN3ME2xMlk{PjJ6IDFOwG0> NHm2TpQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwzQDh2NEGvK|5USU6JRWK8M4E,
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NCI-H1693 NEfKRYlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2m3ZWlEPTB;MT65PVg5QCBizszN MVe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyyPFg1PDFxJ{7TRW5ITVJ:L3G+
OVCAR-4 MV7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3vTb2lEPTB;Mj6wNFQ{PSBizszN MVu8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyyPFg1PDFxJ{7TRW5ITVJ:L3G+
SK-HEP-1 NFjONJZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFrQb49KSzVyPUKuNFA4PDViIN88US=> NFH3V4I9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwzQDh2NEGvK|5USU6JRWK8M4E,
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HT29 NHu3VnBCdnSrcILvcIln\XKjdHn2[UBie3OjeR?= MnHiOFghcHK| NVrPVmVHSW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDIWFI6KGOnbHzzJIFnfGW{IES4JIhzeyCkeTDzeYxnd3Kqb3ThcYlv\SCEIHHzd4F6NCCJSUWwJF0hOS5zNzFOwG0v M2jLUFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF6NEi1O|E2Lz5zOES4OVcyPTxxYU6=
BA/F3 NF3DbVdEgXSxdH;4bYNqfHliYYPzZZk> Mn\rO|IhcHK| MUXDfZRwfG:6aXPpeJkh[WejaX7zeEBud3W|ZTDCRU9HOyClZXzsd{BmgHC{ZYPzbY5oKEKFUj3BRmwhXDNzNVmgcZV1[W62IHHmeIVzKDd{IHjyd{BjgSCPVGSgZZN{[XluIFnDOVAhRSB|LkKg{txONg>? M1qwWVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4OEG0PFkxLz5{NkixOFg6ODxxYU6=
HeLa NGjBNGlHfW6ldHnvckBie3OjeR?= M{TQcFQvPSCqcoO= NGHZUXpKdmirYnn0bY9vKG:oIFXic4xifmm{dYOg[4x6[2:ycn;0[YlvN22jdILpfEBxem:2ZXnuJHZRPDBiZX70dpkhcW5iaIXtZY4hUGWOYTDj[YxteyCjZoTldkA1NjViaILzJIJmfGFvbHHjeIFu[XOnIILldI9zfGW{IHHzd4F6NCCLQ{WwJF0hOy56NTFOwG0v MWC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTZ{NEO4O{c,Ojl4MkSzPFc9N2F-
HT29 MoKzRY51cXC{b3zp[oVz[XSrdnWgZZN{[Xl? MknnOFghcHK| MWTBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKEiWMkmgZ4VtdHNiYX\0[ZIhPDhiaILzJIJ6KHO3bH\vdohw\GGvaX7lJGIh[XO|YYmsJGlEPTBiPTCzMlg4KM7:TT6= MWq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQDR6NUexOUc,OTh2OEW3NVU9N2F-
HepG2 M2fRbmFvfGmycn;sbYZmemG2aY\lJIF{e2G7 NWHOUXZ3PDhiaILz MojYRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDoeY1idiCKZYDHNkBk\WyuczDh[pRmeiB2ODDodpMh[nlic4Xs[o9zcG:mYX3pcoUhSiCjc4PhfUwhUUN3MDC9JFMvQTFizszNMi=> M{jHcFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF6NEi1O|E2Lz5zOES4OVcyPTxxYU6=
HT29 M3LBS2FvfGmycn;sbYZmemG2aY\lJIF{e2G7 NVPnT2J3PDhiaILz MnHERY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDoeY1idiCKVEK5JINmdGy|IHHmeIVzKDR6IHjyd{BjgSC|dXzmc5Jpd2SjbXnu[UBDKGG|c3H5MEBVT0liPTC2MlUh|ryPLh?= NXTZeGluRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUi0PFU4OTVpPkG4OFg2PzF3PD;hQi=>
HepG2 NVzwVIVwSW62aYDyc4xq\mW{YYTpeoUh[XO|YYm= M2TycFQ5KGi{cx?= NGT6fmxCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIFjldGczKGOnbHzzJIFnfGW{IES4JIhzeyCkeTDzeYxnd3Kqb3ThcYlv\SCEIHHzd4F6NCCWR1mgQUA4NjZ4IN88UU4> MnrQQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTh2OEW3NVUoRjF6NEi1O|E2RC:jPh?=
Ba/F3 NHm4U4hE\WyuIHTlZZRpKGG|c3H5 MYrJcoR2[3Srb36gc4Yh[2WubDDk[YF1cCCxZjDteZJqdmViQnHGN{Bk\WyuczDlfJBz\XO|aX7nJG5RVS:DTFugUFI2PlRibYX0ZY51KGK7IITyfZBidiCkbIXlJIV5[2y3c3nvckBie3OjeR?= NIjlS|k9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zNkm3NFQxOCd-MU[5O|A1ODB:L3G+
A673 MoP4dWhVWyCjc4PhfS=> MmH5dWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[|ohWHKrbXHyfUB{[3KnZX6g[o9zKEF4N{OgZ4VtdHN? M3vmNlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
DAOY M{H0T5FJXFNiYYPzZZk> NYH1WWV7eUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC|Y4Ll[Y4h\m:{IFTBU3kh[2WubIO= NGjxfZk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N|UyOzl:L3G+
Saos-2 MX7xTHRUKGG|c3H5 M3vWc5FJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCVYX;zMVIh[2WubIO= MkiyQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN|koRjJ7NEO1NVM6RC:jPh?=
RD NW\0PIpKeUiWUzDhd5NigQ>? NFHtZZRyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiUlSgZ4VtdHN? NFO0OJc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N|UyOzl:L3G+
OHS-50 NW\GZWd4eUiWUzDhd5NigQ>? M2XvTJFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCRSGOtOVAh[2WubIO= M{TjOVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
SK-N-MC MUDxTHRUKGG|c3H5 NYPRWWZ5eUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC|Y4Ll[Y4h\m:{IGPLMW4uVUNiY3XscJM> MkPCQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN|koRjJ7NEO1NVM6RC:jPh?=
Assay
Methods Test Index PMID
Western blot p-Src / Src / p-c-Abl / c-Abl / p-S6 / S6 / p-ERK / ERK / p-STAT3 / STAT3 ; p-FAK / FAK / p-Pyk2 / p-p130Cas / p-AKT ; p-ABL / ABL 27903968 18483306 28199182
Immunofluorescence p-FAK / p-STAT3 / beta-catenin 18483306
Growth inhibition assay Cell viability ; IC50 24812339 27903968
In vivo

Bosutinib (60 mg/kg/day) is active against Src-transformed fibroblasts xenografts and HT29 xenografts in nude mice with T/C of 18% and 30%, respectively. [1] Oral administration of Bosutinib for 5 days significantly suppresses K562 tumor growth in mice in a dose-dependent manner, with the large tumors eradicated at dose of 100 mg/kg and tumor free at 150 mg/kg without overt toxicity. [2] As being inactive against Colo205 xenografts in nude mice at 50 mg/kg twice daily, Bosutinib dosing at 75 mg/kg twice daily is necessary against Colo205 xenografts, and increasing the dose of Bosutinib has no additional benefit, in contrast to the significant dose-dependent ability against HT29 xenografts. [4]

Protocol (from reference)

Kinase Assay:

[1]

  • The Src and Abl kinase assays:

    The Src kinase activity is measured in an ELISA format. Src (3 units/reaction), reaction buffer (50 mM Tris-HCl pH 7.5, 10 mM MgCl2, 0.1 mM EGTA, 0.5 mM Na3VO4) and cdc2 substrate peptide are added to various concentration of Bosutinib and incubated at 30 °C for 10 minutes. The reaction is started by the addition of ATP to a final concentration of 100 μM, incubated at 30 °C for 1 hour and stopped by addition of EDTA. Instructions from the manufacturer are followed for subsequent steps. The Abl kinase assay is performed in a DELFIA solid phase europium-based detection assay format. Biotinylated peptide (2 μM) is bound to streptavidin-coated microtitration plates for 1.5 hours in 1 mg/mL ovalbumin in PBS. The plates are washed for 1 hour with PBS/0.1% Tween 80, followed by a PBS wash. The kinase reaction is incubated for 1 hour at 30°C. Abl kinase (10 units) is mixed with 50 mM Tris-HCl (pH 7.5), 10 mM MgCl2, 80 μM EGTA, 100 μM ATP, 0.5 mM Na3VO4, 1% DMSO, 1 mM HEPES (pH 7.0), 200 μg/mL ovalbumin and various concentration of Bosutinib. The reaction is stopped with EDTA at a final concentration of 50 mM. The reaction is monitored with Eu-labeled phosphotyrosine antibody and DELFIA enhancement solution.

Cell Research:

[2]

  • Cell lines: Abl-MLV, Rat 2, KU812, K562, and MEG-01 cells
  • Concentrations: Dissolved in DMSO, final concentrations ~1 μM
  • Incubation Time: 72 hours
  • Method:

    Cells are exposed to various concentrations of Bosutinib for 72 hours. Anchorage-independent proliferation of Abl-MLV-transformed fibroblasts is measured in 96-well ultra-low binding plates treated with Sigmacote to block residual cell attachment. Cell proliferation is measured with MTS or Cell-Glo. For the determination of cell cycle or cell death, cells are prepared for FACS analysis in the CycleTest Plus DNA reagent kit and analyzed on a fluorescence-activated cell sorter flow cytometer.

  • (Only for Reference)
Animal Research:

[2]

  • Animal Models: Nude female mice injected with K562 cells
  • Dosages: ~150 mg/kg/day
  • Administration: Oral gavage
  • (Only for Reference)

Solubility (25°C)

In vitro

DMSO 100 mg/mL
(188.51 mM)
Ethanol 2 mg/mL
(3.77 mM)
Water Insoluble

In vivo

Add solvents to the product individually and in order
(Data is from Selleck tests instead of citations):
2% DMSO+30% PEG 300+5% Tween 80+ddH2O
For best results, use promptly after mixing.

10mg/mL

* 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 Information

Molecular Weight 530.45
Formula

C26H29Cl2N5O3

CAS No. 380843-75-4
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles CN1CCN(CC1)CCCOC2=C(C=C3C(=C2)N=CC(=C3NC4=CC(=C(C=C4Cl)Cl)OC)C#N)OC

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

Clinical Trial Information

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT04258943 Recruiting Drug: Bosutinib Philadelphia Chromosome Positive CML|Accelerated Phase Chronic Myelogenous Leukemia|Blastic Phase Chronic Myelogenous Leukemia|Chronic Phase Chronic Myelogenous Leukemia Children''s Oncology Group|Erasmus MC|Dutch Childhood Oncology Group|Innovative Therapies for Children with Cancer|Pfizer April 6 2020 Phase 1|Phase 2
NCT03023319 Recruiting Drug: Bosutinib|Drug: Pemetrexed Carcinoma Non-Small-Cell Lung|Mesothelioma|Bladder Cancer|Ovarian Cancer|Peritoneal Cancer|Thymoma|Thymus Cancer|Uterine Cervical Cancer Nagla Abdel Karim|Augusta University December 10 2019 Phase 1
NCT03888222 Active not recruiting Drug: Placebo Oral Tablet|Drug: Bosutinib Oral Tablet Dementia With Lewy Bodies Georgetown University|Alzheimer''s Association April 23 2019 Phase 2
NCT03854903 Recruiting Drug: Palbociclib|Drug: Bosutinib|Drug: Fulvestrant Metastatic Breast Cancer|Human Epidermal Growth Factor 2 Negative Carcinoma of Breast|Hormone Receptor Positive Breast Cancer Georgetown University|Pfizer April 1 2019 Phase 1
NCT03831776 Recruiting Drug: Bosutinib|Drug: Ropeginterferon Chronic Myeloid Leukemia St. Olavs Hospital|Haukeland University Hospital|Oslo University Hospital|University Hospital of North Norway|Helse Stavanger HF|Henri Mondor University Hospital|Hôpital René Huguenin|Hôpital Mignot Versailles Paris|Uppsala University Hospital|Odense University Hospital March 25 2019 Phase 2

(data from https://clinicaltrials.gov, updated on 2021-09-06)

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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Frequently Asked Questions

Question 1:
Can I give S1014 Bosutinib to mice by oral gavage? If so, how to dissolve the drug?

Answer:
For oral gavage, S1014 Bosutinib can be dissolved in 5% Tween 80+0.5% CMC Na at 30 mg/ml as a suspension.

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