Dovitinib (TKI-258)

For research use only.

Catalog No.S1018 Synonyms: CHIR-258

38 publications

Dovitinib (TKI-258) Chemical Structure

CAS No. 405169-16-6

Dovitinib (TKI258, CHIR258) is a multitargeted RTK inhibitor, mostly for class III (FLT3/c-Kit) with IC50 of 1 nM/2 nM, also potent to class IV (FGFR1/3) and class V (VEGFR1-4) RTKs with IC50 of 8-13 nM, less potent to InsR, EGFR, c-Met, EphA2, Tie2, IGF-1R and HER2 in cell-free assays. Phase 4.

Selleck's Dovitinib (TKI-258) has been cited by 38 publications

Purity & Quality Control

Choose Selective FLT3 Inhibitors

Biological Activity

Description Dovitinib (TKI258, CHIR258) is a multitargeted RTK inhibitor, mostly for class III (FLT3/c-Kit) with IC50 of 1 nM/2 nM, also potent to class IV (FGFR1/3) and class V (VEGFR1-4) RTKs with IC50 of 8-13 nM, less potent to InsR, EGFR, c-Met, EphA2, Tie2, IGF-1R and HER2 in cell-free assays. Phase 4.
Targets
FLT3 [1]
(Cell-free assay)
c-Kit [1]
(Cell-free assay)
FGFR1 [1]
(Cell-free assay)
VEGFR3/FLT4 [1]
(Cell-free assay)
FGFR3 [1]
(Cell-free assay)
1 nM 2 nM 8 nM 8 nM 9 nM
In vitro

Dovitinib potently inhibits the FGF-stimulated growth of WT and F384L-FGFR3-expressing B9 cells with IC50 of 25 nM. In addition, Dovitinib inhibits proliferation of B9 cells expressing each of the various activated mutants of FGFR3. Interestingly, there are minimal observed differences in the sensitivity of the different FGFR3 mutations to Dovitinib, with the IC50 ranging from 70 to 90 nM for each of the various mutations. IL-6-dependent B9 cells containing vector only (B9-MINV cells are resistant to the inhibitory activity of Dovitinib at concentrations up to 1 μM. Dovitinib inhibits cell proliferation of KMS11 (FGFR3-Y373C), OPM2 (FGFR3-K650E), and KMS18 (FGFR3-G384D) cells with IC50 of 90 nM (KMS11 and OPM2) and 550 nM, respectively. Dovitinib inhibits FGF-mediated ERK1/2 phosphorylation and induces cytotoxicity in FGFR3-expressing primary MM cells. BMSCs does confer a modest degree of resistance with 44.6% growth inhibition for cells treated with 500 nM Dovitinib and cultured on stroma compared with 71.6% growth inhibition for cells grown without BMSCs. Dovitinib inhibits proliferation of M-NFS-60, an M-CSF growth-driven mouse myeloblastic cell line with a median effective concentration (EC50) of 220 nM. [1] Treatment of SK-HEP1 cells with Dovitinib results in a dose-dependent reduction in cell number and G2/M phase arrest with reduction in the G0/G1 and S phases, inhibition of anchorage-independent growth and blockage of bFGF-induced cell motility. The IC50 for Dovitinib in SK-HEP1 cells is approximately 1.7 μM. Dovitinib also significantly reduces the basal phosphorylation levels of FGFR-1, FGFR substrate 2α (FRS2-α) and ERK1/2 but not Akt in both SK-HEP1 and 21-0208 cells. In 21-0208 HCC cells, Dovitinib significantly inhibits bFGF-induced phosphorylation of FGFR-1, FRS2-α, ERK1/2 but not Akt. [2]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
SupB15 NYfNfWJNT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M37XUGlEPTB;MD60OFkh|ryP MnnCQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV{MEKwO|MoRjJ3MkCyNFc{RC:jPh?=
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BaF3-pSRα MlzzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXHDV5RYUUN3ME2wMlY3QCEQvF2= M3n2OVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3MkCyNFc{Lz5{NUKwNlA4OzxxYU6=
BaF3-p210Bcr-Abl Ml7QS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFvXVG9KSzVyPUCuOlkzKM7:TR?= NVK5e2x[RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkWyNFIxPzNpPkK1NlAzODd|PD;hQi=>
BaF3-p210Bcr-Abl-T315I NGrVUlhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXPJR|UxRTJwNkK2JO69VQ>? MXG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTJyMkC3N{c,OjV{MEKwO|M9N2F-
CCRF-CEM M1SxPGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXzJR|UxRTBwM{m4JO69VQ>? NETEPIE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUKwNlA4Oid-MkWyNFIxPzJ:L3G+
CEM/C2 MXXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NV3UbnRiUUN3ME2xMlEzPSEQvF2= MmXQQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV{MEKwO|IoRjJ3MkCyNFczRC:jPh?=
Nalm-6 Mmf4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MW\JR|UxRTBwM{iyJO69VQ>? NFjJRY09[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUKwNlA4Oid-MkWyNFIxPzJ:L3G+
SEM-K2 Mn;6S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFfLc2FKSzVyPUCuNFIzKM7:TR?= NXLuWFhsRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkWyNFIxPzJpPkK1NlAzODd{PD;hQi=>
HB-1119 NIX3N3FIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHzDcoxKSzVyPUCuNFI5KM7:TR?= NEP6UHo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUKwNlA4Oid-MkWyNFIxPzJ:L3G+
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HCT-116 NXX0S2QzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MkPITWM2OD1|LkC1NE42QCEQvF2= MXq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDR7NUe1NEc,OjR2OUW3OVA9N2F-
HT-29 NXfBOVRET3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1XBc2lEPTB;NT6yNU46OyEQvF2= NE\TbWg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NES5OVc2OCd-MkS0PVU4PTB:L3G+
SW-480 NYTxXGdtT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUfJR|UxRTRwM{OwMlQ4KM7:TR?= MoHPQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR2OUW3OVAoRjJ2NEm1O|UxRC:jPh?=
CaCO2 MVPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MorFTWM2OD1|LkKzNE43PCEQvF2= NGe3U|A9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NES5OVc2OCd-MkS0PVU4PTB:L3G+
LS174T MkDzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3HPe2lEPTB;ND6zN|AvPDdizszN NFTrb5E9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NES5OVc2OCd-MkS0PVU4PTB:L3G+
HEC-1A MkTCSpVv[3Srb36gRZN{[Xl? Ml;WNE4xPS9yLkGvNE42KM7:TR?= NEXubZQ4OiCq NFrmU5Fk[XW|ZYOgZUBl\WO{ZXHz[UBqdiCVVFHUN{whTVKNLDDhcoQhSUuWIIDoc5NxcG:{eXzheIlwdg>? M{DRU|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2NEm1O|UxLz5{NES5OVc2ODxxYU6=
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MFE-296  M4TBbGZ2dmO2aX;uJGF{e2G7 MVewMlA2NzBwMT:wMlUh|ryP MXi3NkBp NUT2WJpW[2G3c3XzJIEh\GWlcnXhd4UhcW5iU2TBWFMtKEWUSzygZY5lKEGNVDDwbI9{eGixconsZZRqd25? MUi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDR7NUe1NEc,OjR2OUW3OVA9N2F-
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BFTC905 NV75bFk6S2WubDDWbYFjcWyrdImgRZN{[Xl? MUKxMVExKM7:TR?= NVnhWGtnPzJiaB?= NYLnSFlDcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? NUT5SGR2RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSzNlU1PjFpPkK0N|I2PDZzPD;hQi=>
TCC-SUP NYq5[IJbS2WubDDWbYFjcWyrdImgRZN{[Xl? NGflT5IyNTFyIN88US=> MVe3NkBp MmfwbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> MV[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDN{NUS2NUc,OjR|MkW0OlE9N2F-
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CNE2  M1\CZWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MV2wMlEuOTBizszN M4H1PFQ5yqCq NFrtU5FqdmS3Y3XzJGczN01iZHXsZZkhcW5iYTDjc45k\W62cnH0bY9vNWSncHXu[IVvfCCvYX7u[ZI> NUXSUW96RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSyN|gxQTRpPkK0NlM5ODl2PD;hQi=>
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HepG2 MV;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXfyTllxPDhiaB?= Mn\pTWM2OD1{LkeyO{DDuSByLkSyPUDPxE1? M{LBZlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ|NUS2OVkyLz5{M{W0OlU6OTxxYU6=
Hep3B MkHjS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NIHz[mc1QCCq NGn2fWFKSzVyPUSuNlI{KMLzIECuPFM6KM7:TR?= NWq3XI83RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO1OFY2QTFpPkKzOVQ3PTlzPD;hQi=>
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Huh7 MWnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlLhOFghcA>? NVfLeGVLUUN3ME2xOU4xODdiwsGgO{4{OzRizszN MUS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzV2NkW5NUc,OjN3NE[1PVE9N2F-
HepG2 NHLCeXVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3i4fFczKGh? MX3JR|UxRTFwMkCwJOKyKDBwMkK2JO69VQ>? MWe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzV2NkW5NUc,OjN3NE[1PVE9N2F-
Hep3B M4H5e2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVu3NkBp NHLrS3FKSzVyPUCuPFkzKMLzIECuNFQ1KM7:TR?= Ml;UQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN3NE[1PVEoRjJ|NUS2OVkyRC:jPh?=
PLC/PRF5 MkG4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEnHdZY4OiCq NH3ofnlKSzVyPUOuNVExKMLzIECuN|M4KM7:TR?= MX28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzV2NkW5NUc,OjN3NE[1PVE9N2F-
Huh7 NIrGPYVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHP5V|U4OiCq MX3JR|UxRTNwOUiwJOKyKDBwOECzJO69VQ>? MlTyQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN3NE[1PVEoRjJ|NUS2OVkyRC:jPh?=
MFE280 MmHWS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlnzTWM2OD1yLkSyJOKyKDBwME[g{txO NIPJPGM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{S0N|gxPSd-MkO0OFM5ODV:L3G+
AN3CA MnPGS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MY\JR|UxRTBwNUCgxtEhOC5zMDFOwG0> NHW3bpo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{S0N|gxPSd-MkO0OFM5ODV:L3G+
HEC155 NUTVdXRwT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXrJR|UxRTBwNk[gxtEhOC5yOTFOwG0> NIjOU489[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{S0N|gxPSd-MkO0OFM5ODV:L3G+
MFE296 MVnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Moq5TWM2OD1yLk[2JOKyKDBwMUmg{txO MVG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzR2M{iwOUc,OjN2NEO4NFU9N2F-
SPAC1S MW\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MX3JR|UxRTBwN{egxtEhOC5yODFOwG0> NXHzco4{RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO0OFM5ODVpPkKzOFQ{QDB3PD;hQi=>
RL952 NWCxZZZsT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVGw[ZlXUUN3ME2wMlk{KMLzIECuNFEh|ryP MlThQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN2NEO4NFUoRjJ|NESzPFA2RC:jPh?=
EN1 MXPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFSyT2ZKSzVyPUGuNFIhyrFiMD6yOUDPxE1? M3TWVVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ|NESzPFA2Lz5{M{S0N|gxPTxxYU6=
SNGII MXjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mk\uTWM2OD1zLkK0JOKyKDBwMkig{txO M4nvdlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ|NESzPFA2Lz5{M{S0N|gxPTxxYU6=
ISHIKAWA NUWwd4tbT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3zpeGlEPTB;MT6zNEDDuSByLkGxJO69VQ>? MV[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzR2M{iwOUc,OjN2NEO4NFU9N2F-
HEC1A MVfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGr5eWtKSzVyPUGuN|QhyrFiMD6zNEDPxE1? NETFSJg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{S0N|gxPSd-MkO0OFM5ODV:L3G+
KLE MYjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3Pr[mlEPTB;MT6zO{DDuSByLkCyJO69VQ>? NIi5WIo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{S0N|gxPSd-MkO0OFM5ODV:L3G+
SNGM NHW5XW9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWK3V2l6UUN3ME2xMlQzKMLzIECuNVMh|ryP M13lR|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ|NESzPFA2Lz5{M{S0N|gxPTxxYU6=
USPC2 M2DmbWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NY[4b3BRUUN3ME2xMlYzKMLzIECuNFEh|ryP MnrsQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN2NEO4NFUoRjJ|NESzPFA2RC:jPh?=
EN NY[yWJJyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXLJR|UxRTFwNk[gxtEhOC5yMTFOwG0> MoTYQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN2NEO4NFUoRjJ|NESzPFA2RC:jPh?=
MFE319 MWfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkT3TWM2OD1zLki3JOKyKDBwNEWg{txO NHftU|c9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{S0N|gxPSd-MkO0OFM5ODV:L3G+
EFE184 MmTBS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M33JOGlEPTB;Mj6wOEDDuSByLkGzJO69VQ>? MVu8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzR2M{iwOUc,OjN2NEO4NFU9N2F-
ECC1 MVjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4HEcGlEPTB;Mj6wO{DDuSByLkCxJO69VQ>? M{fRXVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ|NESzPFA2Lz5{M{S0N|gxPTxxYU6=
HEC1B M4XXemdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4\XR2lEPTB;Mj61O{DDuSByLkKzJO69VQ>? MYS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzR2M{iwOUc,OjN2NEO4NFU9N2F-
USPC1 Mnj6S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVLJR|UxRTJwNkCgxtEhOC5zMzFOwG0> MVO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzR2M{iwOUc,OjN2NEO4NFU9N2F-
SPAC1L MXzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MoHSTWM2OD1|LkC2JOKyKDFwMUSg{txO MoHjQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN2NEO4NFUoRjJ|NESzPFA2RC:jPh?=
HUVEC NEjGWYVE\WyuIG\pZYJqdGm2eTDBd5NigQ>? M1LQNVAuOjVizszN Mo\0O|IhcA>? NVLLU|BJTE2VTx?= NGXYZVFqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? NYW5[JQ5RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkOyNlgxOTdpPkKzNlI5ODF5PD;hQi=>
HMVEC MW\D[YxtKF[rYXLpcIl1gSCDc4PhfS=> MoXHNE0zPSEQvF2= MoPTO|IhcA>? M37DT2ROW09? MnXibY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> NVPoSotORGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkOyNlgxOTdpPkKzNlI5ODF5PD;hQi=>
MHCC-97H MoWxR4VtdCCYaXHibYxqfHliQYPzZZk> NW\iNYl6OC1{NTFOwG0> Moi3O|IhcA>? NYO3Z2VSTE2VTx?= M4HqRYlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz M{TsRlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ|MkK4NFE4Lz5{M{KyPFAyPzxxYU6=
SMMC7721 NFTWeYRE\WyuIG\pZYJqdGm2eTDBd5NigQ>? MmXHNE0zPSEQvF2= NXKzUZUzPzJiaB?= MlLzSG1UVw>? M4joVYlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz NYTV[ZpPRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkOyNlgxOTdpPkKzNlI5ODF5PD;hQi=>
Huh-7 M{PQXWFxd3C2b4Ppd{BCe3OjeR?= M2nJcFAuOTJwNTFOwG0> NV;JXmlkOjRiaB?= NHS4RpVFVVORwrC= MYrz[Y5{cXSrenXzJGhESyClZXzsd{B1dyCWUlHJUE0h[W6mIITp[4F1fXq3bXHiMYlv\HWlZXSgZZBweHSxc3nzJIlvKGFiZH;z[U1l\XCnbnTlcpQhdWGwbnXy MlnLQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ{M{C0O|koRjJ{MkOwOFc6RC:jPh?=
Sk-Hep1 MojsRZBweHSxc3nzJGF{e2G7 NVLs[ndwOC1zMj61JO69VQ>? MlrTNlQhcA>? NVTwfIE6TE2VT9Mg M2ribJNmdnOrdHn6[ZMhUEOFIHPlcIx{KHSxIGTSRWlNNSCjbnSgeIlo[XS3eoXtZYIucW6mdXPl[EBieG:ydH;zbZMhcW5iYTDkc5NmNWSncHXu[IVvfCCvYX7u[ZI> M4PmTFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{MkOwOFc6Lz5{MkKzNFQ4QTxxYU6=
Hep3B MWPBdI9xfG:|aYOgRZN{[Xl? NV3wW2lYOC1zMj61JO69VQ>? NHfyPZozPCCq M{LqWWROW00EoB?= NVjTZ5Rke2Wwc3n0bZpmeyCKQ1OgZ4VtdHNidH:gWHJCUUxvIHHu[EB1cWejdIX6eY1i[i2rbnT1Z4VlKGGyb4D0c5NqeyCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5meg>? NUfSbpdiRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkKyN|A1PzlpPkKyNlMxPDd7PD;hQi=>
PLC5 MVTBdI9xfG:|aYOgRZN{[Xl? MUmwMVEzNjVizszN MYmyOEBp MlnxSG1UV8Li MVPz[Y5{cXSrenXzJGhESyClZXzsd{B1dyCWUlHJUE0h[W6mIITp[4F1fXq3bXHiMYlv\HWlZXSgZZBweHSxc3nzJIlvKGFiZH;z[U1l\XCnbnTlcpQhdWGwbnXy MYG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjJ|MES3PUc,OjJ{M{C0O|k9N2F-
PLC5 NELv[WdE\WyuIG\pZYJqdGm2eTDBd5NigQ>? M2nSU|AuOTVizszN M4DHXlczKGh? MW\y[YR2[2W|IHPlcIwhfmmjYnnsbZR6KGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVzyqB? NGrGfHg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkG4NFMxQCd-MkKxPFA{ODh:L3G+
Hep3B Moj5R4VtdCCYaXHibYxqfHliQYPzZZk> MkDsNE0yPSEQvF2= M4HZUVczKGh? NETscpBz\WS3Y3XzJINmdGxidnnhZoltcXS7IHnuJIEh\G:|ZT3k[ZBmdmSnboSgcYFvdmW{wrC= MoO3QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJzOECzNFgoRjJ{MUiwN|A5RC:jPh?=
Sk-Hep1 NX;t[XpvS2WubDDWbYFjcWyrdImgRZN{[Xl? MVOwMVE2KM7:TR?= MX:3NkBp MonGdoVlfWOnczDj[YxtKH[rYXLpcIl1gSCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5mesLi NGXwSoM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkG4NFMxQCd-MkKxPFA{ODh:L3G+
Huh-7 NWnENndiS2WubDDWbYFjcWyrdImgRZN{[Xl? NVP3b5hvOC1zNTFOwG0> NEXEUXQ4OiCq MlfudoVlfWOnczDj[YxtKH[rYXLpcIl1gSCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5mesLi MUC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjF6MEOwPEc,OjJzOECzNFg9N2F-
PLC5 Mn;JRZBweHSxc3nzJGF{e2G7 MnX1NE0yPSEQvF2= NWX1NGo5OjRiaB?= NFv6SllqdmO{ZXHz[ZMh[XCxcITveIlkKGOnbHyg[IVifGhiaX6gZUBld3OnLXTldIVv\GWwdDDtZY5v\XMEoB?= MX[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjF6MEOwPEc,OjJzOECzNFg9N2F-
Hep3B NUHwXlNjSXCxcITvd4l{KEG|c3H5 M1TNS|AuOTVizszN M{O3bVI1KGh? NULIfW5TcW6lcnXhd4V{KGGyb4D0c5Rq[yClZXzsJIRm[XSqIHnuJIEh\G:|ZT3k[ZBmdmSnboSgcYFvdmW{wrC= NF3VXZI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkG4NFMxQCd-MkKxPFA{ODh:L3G+
Sk-Hep1 NF3Ob|dCeG:ydH;zbZMhSXO|YYm= NF\TOpgxNTF3IN88US=> NGrN[pYzPCCq MmL3bY5kemWjc3XzJIFxd3C2b4TpZ{Bk\WyuIHTlZZRpKGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVzyqB? MoPxQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJzOECzNFgoRjJ{MUiwN|A5RC:jPh?=
Huh-7 NGfm[nFCeG:ydH;zbZMhSXO|YYm= NWXufHNMOC1zNTFOwG0> M3fWblI1KGh? NF;mcVhqdmO{ZXHz[ZMh[XCxcITveIlkKGOnbHyg[IVifGhiaX6gZUBld3OnLXTldIVv\GWwdDDtZY5v\XMEoB?= MoflQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJzOECzNFgoRjJ{MUiwN|A5RC:jPh?=
PLC5 M3X2c2Z2dmO2aX;uJGF{e2G7 MlXmNE0yOCEQvF2= Mn7oNlQhcA>? NInC[HJk[XW|ZYOg[I9{\S2mZYDlcoRmdnRiRF7BJIZz[WevZX70ZZRqd25? M4\PWlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{MUiwN|A5Lz5{MkG4NFMxQDxxYU6=
Hep3B M1PESWZ2dmO2aX;uJGF{e2G7 NULNNGRlOC1zMDFOwG0> MWOyOEBp M{\LfYNifXOnczDkc5NmNWSncHXu[IVvfCCGTlGg[pJi\22nboTheIlwdg>? NFTa[5M9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkG4NFMxQCd-MkKxPFA{ODh:L3G+
Sk-Hep1 MVLGeY5kfGmxbjDBd5NigQ>? NXO2VJM{OC1zMDFOwG0> M4ixeVI1KGh? NF;t[2Vk[XW|ZYOg[I9{\S2mZYDlcoRmdnRiRF7BJIZz[WevZX70ZZRqd25? NXvXOHNsRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkKxPFA{ODhpPkKyNVgxOzB6PD;hQi=>
Huh-7 NYHHN2VCTnWwY4Tpc44hSXO|YYm= MUCwMVExKM7:TR?= MYOyOEBp NYrIeWJj[2G3c3XzJIRwe2VvZHXw[Y5l\W62IFTORUBnemGpbXXueIF1cW:w Mm\lQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJzOECzNFgoRjJ{MUiwN|A5RC:jPh?=
SW780 M2rsN2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmDqOUBl NGDtPJBKSzVyPUWwJI5O MmfPQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjFzMUm2OlEoRjJzMUG5OlYyRC:jPh?=
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NB-EBc1 MVPxTHRUKGG|c3H5 NVfDPHRMeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC|Y4Ll[Y4h\m:{IF7CMWVD[zFiY3XscJM> MXS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR|NUGzPUc,Ojl2M{WxN|k9N2F-
U-2 OS NVjFcZY2eUiWUzDhd5NigQ>? MlGydWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[|ohWHKrbXHyfUB{[3KnZX6g[o9zKFVvMjDPV{Bk\Wyucx?= M1rZXlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
Saos-2 MYnxTHRUKGG|c3H5 NX7LcYFKeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC|Y4Ll[Y4h\m:{IGPhc5MuOiClZXzsdy=> M2LZS|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
SK-N-SH NXjUNmVieUiWUzDhd5NigQ>? NVflU5pleUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC|Y4Ll[Y4h\m:{IGPLMW4uW0hiY3XscJM> M{TsN|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
NB1643 M1jyd5FJXFNiYYPzZZk> NETmclFyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiTlKxOlQ{KGOnbHzz MonQQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN|koRjJ7NEO1NVM6RC:jPh?=
LAN-5 MU\xTHRUKGG|c3H5 MVjxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW|IH\vdkBlenWpIILldJVzeG:|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhVEGQLUWgZ4VtdHN? MoTBQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN|koRjJ7NEO1NVM6RC:jPh?=
BT-12 NF\kfY9yUFSVIHHzd4F6 MYPxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW|IH\vdkBlenWpIILldJVzeG:|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhSlRvMUKgZ4VtdHN? Mke2QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN|koRjJ7NEO1NVM6RC:jPh?=
Rh18 MkezdWhVWyCjc4PhfS=> MX3xTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW|IH\vdkBlenWpIILldJVzeG:|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhWmhzODDj[Yxtew>? Mlu1QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN|koRjJ7NEO1NVM6RC:jPh?=
OHS-50 M1rCO5FJXFNiYYPzZZk> NI\mS2VyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiT1jTMVUxKGOnbHzz M3rpVFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
RD M{LTN5FJXFNiYYPzZZk> MmLsdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[|ohWHKrbXHyfUB{[3KnZX6g[o9zKFKGIHPlcIx{ MYi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR|NUGzPUc,Ojl2M{WxN|k9N2F-
insect cells NF;VTZZHfW6ldHnvckBie3OjeR?= Mlj0NUB1dyB2IHjydy=> MWXJcohq[mm2aX;uJI9nKHKnY3;tZolv[W62IF\HSnIyKCi3bnvuc5dvKG:{aXfpckkh\XiycnXzd4VlKGmwIHLhZ5Vtd3[rcoXzJIlv\mWldHXkJIlve2WldDDj[YxteyC3c3nu[{BIT0eJUVTHT2R[UV[OUFmgZZMhe3Wkc4TyZZRmKGGodHXyJFEhfG9iNDDodpMh[nlidHnt[U1z\XOxbI\l[EBndHWxcnXzZ4Vv[2ViYYPzZZktKEmFNUC9NE4xODkQvF2= NGfu[|A9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9|MEWwN|k{QCd-M{C1NFM6Ozh:L3G+
NCI-H1703 MXPGeY5kfGmxbjDhd5NigQ>? NUTVTXhKOTBidV2= Mm\oNlQhcHK| MYHJcohq[mm2aX;uJI9nKFSQSVugbY4hcHWvYX6gUmNKNUhzN{CzJINmdGy|IITyZY5{\mWldHXkJJdqfGhibHXueIl3cXKjbDD2[YN1d3JiN2TGVEBie3Onc4Pl[EBieyC{ZXT1Z5Rqd25ib3[gS3NMOyCrbnjpZol1d3JiWDDhZ5RqfmG2ZXSgWG5KUy2vZXTpZZRm\CCZboSvWGNHN2KndHGtZ4F1\W6rbj3k[ZBmdmSnboSgeJJidnOlcnnweIlwdiCjdDCxNEB2VSCjZoTldkAzPCCqcoOgZpkhdHWlaX\ldoF{\SC{ZYDvdpRmeiCjc4PhfS=> NVuxSYs3RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTJ{OEmyM{c,S2iHTVLMQE9iRg>?
LoVo NU\INJBHS3m2b4TvfIlkcXS7IHHzd4F6 MX[xNEB2VQ>? NHrKbYM4OiCqcoO= M1vGOmN6fG:2b4jpZ4l1gSCjZ3HpcpN1KFewdD;i[ZRiNWOjdHXubY4he2mpbnHscIlv\yCmZYDlcoRmdnRiaIXtZY4hVG:YbzDj[YxteyCjc4Pld5Nm\CCjczDj[YxtKH[rYXLpcIl1gSCjdDCxNEB2VSCjZoTldkA4OiCqcoOgZpkhSVSSbHn0[UBie3OjeR?= NHTNbWc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2OjJ6OUKvK|5EcEWPQly8M4E,
HCT116 MWXDfZRwfG:6aXPpeJkh[XO|YYm= MoDlNVAhfU1? NET1OZc4OiCqcoO= M3XuXWN6fG:2b4jpZ4l1gSCjZ3HpcpN1KFewdD;i[ZRiNWOjdHXubY4he2mpbnHscIlv\yCmZYDlcoRmdnRiaIXtZY4hUEOWMUG2JINmdGy|IHHzd4V{e2WmIHHzJINmdGxidnnhZoltcXS7IHH0JFExKHWPIHHmeIVzKDd{IHjyd{BjgSCDVGDsbZRmKGG|c3H5 NUm1RYtJRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTJ{OEmyM{c,S2iHTVLMQE9iRg>?

... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Western blot
CDK1 / p-CDK1 / p53 / p21 ; 

PubMed: 24238094     


(A) Dovitinib induces phosphorylation of CDK1(Tyr15) in nasopharyngeal carcinoma cells. HONE1 cells were incubated with Dovitinib (5 μM) and harvested at the indicated time-points. Lysates were prepared and the indicated proteins were detected with immunoblotting. Equal loading of lysates was confirmed by immunoblotting for actin. (B) Dovitinib induces phosphorylation of CDK1Tyr15 in HeLa cells. HeLa cells were exposed to the indicated concentrations of Dovitinib for 24 hrs. Lysates were prepared and analysed with immunoblotting. Equal loading of extracts was accessed by immunoblotting of actin. (C) Dovitinib induces phosphorylation of CDK1Tyr15 in Hep3B cells. Hep3B cells were treated with the indicated concentrations of Dovitinib for 24 hrs. Lysates were prepared for immunoblotting analysis. Actin was probed to confirm equal loading. 

p-PDGFR-β / PDGFR-β / p-ERK / ERK ; 

PubMed: 23228017     


Phosphorylation of p-PDGFR-β and p-ERK were inhibited by dovitinib at pharmacologically relevant concentrations in MHCC-97H and SMMC7721 cells.

p-VEGFR-2 / VEGFR-2 / p-FGFR-1 / FGFR-1 ; 

PubMed: 23228017     


Dovitinib inhibited the phosphorylation of FGFG-1, VEGFR-2, and downstream ERK in HMVEC and HUVEC endothelial cells at pharmacologically relevant concentrations.

p-STAT3 / STAT3 / Mcl-1 / LC3 / Beclin 1 / p62 ; 

PubMed: 31485222     


The protein extracts from dovitinib-treated were subjected to immunoblot analysis for p-STAT3, STAT3, Mcl-1, beclin1, LC3B, p62, and actin.

24238094 23228017 31485222
Growth inhibition assay
Cell viability; 

PubMed: 28467797     


Cell viability of peripheral blood mononuclear cells (PBMCs) and RPMI8226 cells treated with dovitinib in RPMI1640 medium containing 5% FBS for 24 h. Data are presented as mean±SD. Experiments were performed in triplicate.* P < 0.01, **P < 0.001 versus control.

28467797
In vivo Dovitinib induces both cytostatic and cytotoxic responses in vivo resulting in regression of FGFR3-expressing tumors.[1] Dovitinib shows a dose- and exposure-dependent inhibition of target receptor tyrosine kinases (RTKs) expressed in tumor xenografts. Dovitinib potently inhibits tumor growth of six HCC lines. Inhibition of angiogenesis correlated with inactivation of FGFR/PDGFRβ/VEGFR2 signaling pathways. In an orthotopic model, Dovitinib potently inhibits primary tumor growth and lung metastasis and significantly prolonged mouse survival. [2] Administration of Dovitinib results in significant tumor growth inhibition and tumor regressions, including large, established tumors (500-1,000 mm3). [3]

Protocol

Kinase Assay:[1]
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In vitro kinase assays:

The inhibitory concentration of 50% (IC50) values for the inhibition of RTKs by Dovitinib are determined in a time-resolved fluorescence (TRF) or radioactive format, measuring the inhibition by Dovitinib of phosphate transfer to a substrate by the respective enzyme. The kinase domains of FGFR3, FGFR1, PDGFRβ, and VEGFR1-3 are assayed in 50 mM HEPES (N-2-hydroxyethylpiperazine-N-2-ethanesulfonic acid), pH 7.0, 2 mM MgCl2, 10 mM MnCl2 1 mM NaF, 1 mM dithiothreitol (DTT), 1 mg/mL bovine serum albumin (BSA), 0.25 μM biotinylated peptide substrate (GGGGQDGKDYIVLPI), and 1 to 30 μM adenosine triphosphate (ATP) depending on the Km for the respective enzyme. ATP concentrations are at or just below Km. For c-KIT and FLT3 reactions the pH is raised to 7.5 with 0.2 to 8 μM ATP in the presence of 0.25 to 1 μM biotinylated peptide substrate (GGLFDDPSYVNVQNL). Reactions are incubated at room temperature for 1 to 4 hours and the phosphorylated peptide captured on streptavidin-coated microtiter plates containing stop reaction buffer (25 mM EDTA [ethylenediaminetetraacetic acid], 50 mM HEPES, pH 7.5). Phosphorylated peptide is measured with the DELFIA TRF system using a Europium-labeled antiphosphotyrosine antibody PT66. The concentration of Dovitinib for IC50 is calculated using nonlinear regression with XL-Fit data analysis software version 4.1 (IDBS). Inhibition of colony-stimulating factor-1 receptor (CSF-1R), PDGFRα, insulin receptor (InsR), and insulin-like growth factor receptor 1 (IGFR1) kinase activity is determined at ATP concentrations close the Km for ATP.
Cell Research:[1]
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  • Cell lines: B9 cells, MM cell lines
  • Concentrations: 100 nM
  • Incubation Time: 48-96 hours
  • Method: Cell viability is assessed by 3-(4,5-dimethylthiazol)-2,5-diphenyl tetrazolium (MTT) dye absorbance. Cells are seeded in 96-well plates at a density of 5 × 103 (B9 cells) or 2 × 104 (MM cell lines) cells per well. Cells are incubated with 30 ng/mL aFGF and 100 μg/mL heparin or 1% IL-6 where indicated and increasing concentrations of Dovitinib. For each concentration of Dovitinib, 10 μL aliquots of drug or DMSO diluted in culture medium is added. For drug combination studies, cells are incubated with 0.5 μM dexamethasone, 100 nM Dovitinib, or both simultaneously where indicated. To evaluate the effect of Dovitinib on growth of MM cells adherent to BMSCs, 104 KMS11 cells are cultured on BMSC-coated 96-well plates in the presence or absence of Dovitinib. Plates are incubated for 48 to 96 hours. For assessment of macrophage colony-stimulating factor (M-CSF)-mediated growth, 5 × 103 M-NFS-60 cells/well are incubated with serial dilutions of Dovitinib with 10 ng/mL M-CSF and without granulocyte-macrophage colony-stimulating factor (GM-CSF). After 72 hours cell viability is determined using Cell Titer-Glo Assay. Each experimental condition is performed in triplicate.
    (Only for Reference)
Animal Research:[1]
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  • Animal Models: 8-week-old female BNX mice bearing KMS11 cells
  • Dosages: 10, 30, or 60 mg/kg
  • Administration: Gavage
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 30 mg/mL (76.44 mM)
Water Insoluble
Ethanol Insoluble
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
For best results, use promptly after mixing.
30 mg/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 392.43
Formula

C21H21FN6O

CAS No. 405169-16-6
Storage powder
in solvent
Synonyms CHIR-258
Smiles CN1CCN(CC1)C2=CC3=C(C=C2)N=C(N3)C4=C(C5=C(C=CC=C5F)NC4=O)N

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
Dosage mg/kg Average weight of animals g Dosing volume per animal ul Number of animals
Step 2: Enter the in vivo formulation ()
% DMSO % % Tween 80 % ddH2O
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Bio Calculators

Molarity Calculator

Molarity Calculator

Calculate the mass, volume or concentration required for a solution. The Selleck molarity calculator is based on the following equation:

Mass (mg) = Concentration (mM) × Volume (mL) × Molecular Weight (g/mol)

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*When preparing stock solutions, please always use the batch-specific molecular weight of the product found on the via label and SDS / COA (available on product pages).

Dilution Calculator

Dilution Calculator

Calculate the dilution required to prepare a stock solution. The Selleck dilution calculator is based on the following equation:

Concentration (start) x Volume (start) = Concentration (final) x Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2 ( Input Output )

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* When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and SDS / COA (available online).

The Serial Dilution Calculator Equation

  • Serial Dilutions

  • Computed Result

  • C1=C0/X C1: LOG(C1):
    C2=C1/X C2: LOG(C2):
    C3=C2/X C3: LOG(C3):
    C4=C3/X C4: LOG(C4):
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Molecular Weight Calculator

Molecular Weight Calculator

Enter the chemical formula of a compound to calculate its molar mass and elemental composition:

Total Molecular Weight: g/mol

Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2

Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter its chemical formula and click 'Calculate'.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT02268435 Withdrawn Drug: dovitinib plus imatinib Gastrointestinal Stromal Tumors Asan Medical Center March 2015 Phase 1
NCT01700270 Completed Drug: dovitinib (TKI258)|Drug: fluvoxamine Advanced Solid Tumors Excluding Breast Cancer Novartis Pharmaceuticals|Novartis May 2013 Phase 1
NCT01680796 Withdrawn Drug: Dovitinib|Drug: Bortezomib|Drug: Dexamethasone Multiple Myeloma University of Florida|Novartis Pharmaceuticals February 2013 Phase 1
NCT01266070 Terminated Drug: Dovitinib Von Hippel-Lindau Syndrome M.D. Anderson Cancer Center|Novartis November 2012 Phase 2
NCT01515969 Terminated Drug: Erlotinib hydrochloride|Drug: Dovitinib lactate Non-small Cell Lung Cancer (NSCLC) Recurrent|Non-small Cell Lung Cancer (NSCLC) Stage IV Heather Wakelee|Genentech Inc.|Novartis|Stanford University July 2012 Phase 1

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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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID