Dovitinib (TKI-258, CHIR-258)

Catalog No.S1018

Dovitinib (TKI-258, CHIR-258) Chemical Structure

Molecular Weight(MW): 392.43

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.

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Cited by 11 Publications

7 Customer Reviews

  •  

    Orthotopic xenografts of HNSCC cell lines (A) SCC-1 and (B) OSC-19 were treated with dovitinib (20 mg/kg/day). In addition, the OSC-19 xenografts were treated with +/ radiation therapy. Marker, mean for triplicate; bars, SE. Statistical significance by unpaired t-test, p < 0.05.

    Oral Oncol 2012 48, 1242-9. Dovitinib (TKI-258, CHIR-258) purchased from Selleck.

    Treatments were initiated at time of orthotopic implantation. Growth stabilization was seen by day 8 of treatment (Fig. B). On day 17, tumors were har-vested and histological analysis was performed (Fig. C). Following Ki67 staining, tumors from control xenografts were found to have a higher percentage of proliferating cells (62%) compared to those treated with dovitinib (14%; p = 0.005). The incidence of lymph nodes metastasis was greater in the control cohort ( n = 15) com-pared to those treated with dovitinib (n = 5).

    Oral Oncol 2012 48, 1242-9. Dovitinib (TKI-258, CHIR-258) purchased from Selleck.

  • Dose–response curves for HNSCC cells and fibroblasts treated in vitro with dovitinib (0–1000 nM). Boxes, mean for triplicate; bars, SE

    Oral Oncol 2012 48, 1242-9. Dovitinib (TKI-258, CHIR-258) purchased from Selleck.

    In vitro assays on CUX1-FGFR1-expressing Ba/F3 cells. a. IL-3 deprivation of Ba/F3 cells transduced with CUX1-FGFR1 resulted in transformation to growth factor independent growth. The mean growth ±SEM of three separate measurements over four consecutive days is presented. b. The dose-response curves of CUX1-FGFR1-transduced Ba/F3 cells, treated with TKI258 and PKC412 for 48 hours in the absence or presence of IL-3 (2 ng/ml) are presented. Points represent the average results of two experiments done in triplicate plotted with the curve-fitting GraphPad Prism 5 software; bars, SD. The calculated IC50 for each inhibitor is indicated. c. Western blot analyses of CUX1-FGFR1-transformed Ba/F3 cells after treatment with PKC412 and TKI258. Phosphorylation of CUX1-FGFR1 and its downstream effectors STAT5 and RPS6K decreased with increasing inhibitor concentrations. Expression of total CUX1-FGFR1, STAT5 and RPS6K remained unaffected. d. Effect of PKC412 and TKI258 on apoptosis of CUX1-FGFR1-expressing Ba/F3 cells after treatment for 48 hours. The percentage of apoptotic plus necrotic CUX1-FGFR1-transduced Ba/F3 cells is indicated.

    Haematologica 2011 96, 922-926. Dovitinib (TKI-258, CHIR-258) purchased from Selleck.

  • Ba/F3 cell lines expressing the recombinant TEL/kinase domain fusion protein for FGFR1-4 .Cells were grown in RPMI 1640 containing 10% FBS and 500 ng/mL puromycin. The parental Ba/F3 cell line transduced with an empty vector was grown in 10 ng/mL IL-3 (R & D systems). Cell viability was assessed at 72 hours using the Cell Titer 96 Aqueous One Solution (Promega). Data were plotted as percent viability relative to vehicle-treated cells and are shown as mean (±SD) from 3 experiments.

    AACR 2011 Dovitinib (TKI-258, CHIR-258) purchased from Selleck.

    RT112 cells were exposed to PD173074 (PD) (500 nM) for 0-24 h, TKI-258 (TK) (500 nM) or SU5402 (SU) (5 nM) for 1 h. Cells were lysed, FGFR3 was immunoprecipitated (immunoprecipitated, IP) and blots (immunoblot, IB) were probed for phospho-tyrosine and reprobed for FGFR3 or probed for phospho-ERK and reprobed for total ERK.

    BRIT J CANCER 2010 104, 75-82. Dovitinib (TKI-258, CHIR-258) purchased from Selleck.

  • Cells were exposed to PD173074 or TKI-258 (500 nM) for 24 h. Cell cycle profile was analysed using the Guava Easycyte Plus flow cytometry system.

    BRIT J CANCER 2010 104, 75-82. Dovitinib (TKI-258, CHIR-258) purchased from Selleck.

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 NFnkdotIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXz1SFNZUUN3ME2wMlQ1QSEQvF2= Mn7aNlUzODJyN{O=
SupB15-R MYPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlrhTWM2OD1yLkW1PEDPxE1? NFzGO20zPTJyMkC3Ny=>
BaF3-pSRα MlyzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MoroTWM2OD1yLk[2PEDPxE1? MoPjNlUzODJyN{O=
BaF3-p210Bcr-Abl MULHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkLJTWM2OD1yLk[5NkDPxE1? M2jvNVI2OjB{MEez
BaF3-p210Bcr-Abl-T315I NFz6RnhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXq5T45MUUN3ME2yMlYzPiEQvF2= NHntRnIzPTJyMkC3Ny=>
CCRF-CEM MonuS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlnVTWM2OD1yLkO5PEDPxE1? NG\6UVkzPTJyMkC3Ni=>
CEM/C2 MXXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWPzW4dIUUN3ME2xMlEzPSEQvF2= NYL3bpVDOjV{MEKwO|I>
Nalm-6 MUjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVPJR|UxRTBwM{iyJO69VQ>? MXmyOVIxOjB5Mh?=
SEM-K2 M{DOZmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGPse2dKSzVyPUCuNFIzKM7:TR?= NXvMU4dMOjV{MEKwO|I>
HB-1119 M1zITWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MV;JR|UxRTBwMEK4JO69VQ>? NGX1[pgzPTJyMkC3Ni=>
RS4:11 NIPNem9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVrJR|UxRTJwOEGg{txO NFjwV4MzPTJyMkC3Ni=>
Nalm-6 MlfpRZBweHSxc3nzJGF{e2G7 NYLXTY5iOiEQvF2= NIHrNYozPC92ODDo NH63fFhqdmS3Y3XzJIFxd3C2b4Ppd{Bz\XO3bITpcochcW5iYXLveZQhPzJnIH;mJINmdGxiZHXheIgh[W[2ZYKgNlQhcCC2cnXheI1mdnRiYX7kJFgyLSCjZoTldkA1QCCq MkPiNlUzODJyN{K=
SEM-K2 MVnBdI9xfG:|aYOgRZN{[Xl? MYSwMlEwOSEQvF2= NGjZTHQzPCCq MVfpcoR2[2W|IHXhdox6KGGyb4D0c5NqeyCxZjDTSW0uUzJiY3XscJMh[XRiMD6xJO69VSCjZoTldkAzPCCq NX;ETplGOjV{MEKwO|I>
HCT-116 MXnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWnJR|UxRTNwMEWwMlU5KM7:TR?= MYGyOFQ6PTd3MB?=
HT-29 MnPoS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXrJR|UxRTVwMkGuPVMh|ryP NX;IUZQzOjR2OUW3OVA>
SW-480 MUnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYDSV4lxUUN3ME20MlM{OC52NzFOwG0> M1O5NFI1PDl3N{Ww
CaCO2 Mn3LS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3jkbWlEPTB;Mz6yN|AvPjRizszN M{LBbVI1PDl3N{Ww
LS174T MVvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYLJR|UxRTRwM{OwMlQ4KM7:TR?= Ml[zNlQ1QTV5NUC=
HEC-1A NWPuTmpqTnWwY4Tpc44hSXO|YYm= M3HmXVAvODVxMD6xM|AvPSEQvF2= MoXwO|IhcA>? NUTqVWdm[2G3c3XzJIEh\GWlcnXhd4UhcW5iU2TBWFMtKEWUSzygZY5lKEGNVDDwbI9{eGixconsZZRqd25? NXn1ToZGOjR2OUW3OVA>
AN3CA NUXycGhJTnWwY4Tpc44hSXO|YYm= M{W3elAvODVxMD6xM|AvPSEQvF2= M3G5XFczKGh? M1SyOoNifXOnczDhJIRm[3KnYYPlJIlvKFOWQWSzMEBGWktuIHHu[EBCU1RicHjvd5Bpd3K7bHH0bY9v NGn3SmEzPDR7NUe1NC=>
MFE-296  MYnGeY5kfGmxbjDBd5NigQ>? MmH1NE4xPS9yLkGvNE42KM7:TR?= NH7re|E4OiCq MWPjZZV{\XNiYTDk[YNz\WG|ZTDpckBUXEGWMzygSXJMNCCjbnSgRWtVKHCqb4PwbI9zgWyjdHnvci=> M4jMclI1PDl3N{Ww
UMC3 NI\jbGlE\WyuIG\pZYJqdGm2eTDBd5NigQ>? NVPHbFJiOS1zMDFOwG0> NXvzVmJlPzJiaB?= NEDRTlhqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? NGLLR40zPDN{NUS2NS=>
5637 MXTD[YxtKF[rYXLpcIl1gSCDc4PhfS=> MlvhNU0yOCEQvF2= NWDzRlRPPzJiaB?= M2rtWYlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz MofFNlQ{OjV2NkG=
HU456 MYDD[YxtKF[rYXLpcIl1gSCDc4PhfS=> NXrnfnNDOS1zMDFOwG0> MmTLO|IhcA>? MXnpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> NEjEXWczPDN{NUS2NS=>
MGHU4 NVzObmtDS2WubDDWbYFjcWyrdImgRZN{[Xl? MUKxMVExKM7:TR?= M4f5OVczKGh? MUTpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> NED5WoUzPDN{NUS2NS=>
HT1376 NVvweYFOS2WubDDWbYFjcWyrdImgRZN{[Xl? NFv5S4IyNTFyIN88US=> NHnTR|k4OiCq M{XQcolvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz NU\1V5FWOjR|MkW0OlE>
RT112 MlPSR4VtdCCYaXHibYxqfHliQYPzZZk> MkS0NU0yOCEQvF2= MXe3NkBp MoK5bY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> NVT2cY1QOjR|MkW0OlE>
T24 NHfhO|dE\WyuIG\pZYJqdGm2eTDBd5NigQ>? M2XF[lEuOTBizszN M3rtdlczKGh? MYXpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> MV6yOFMzPTR4MR?=
BFTC905 NHqxWYlE\WyuIG\pZYJqdGm2eTDBd5NigQ>? NV7LUmV[OS1zMDFOwG0> NVvxWVdOPzJiaB?= NXX1Zm1McW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? NXfiWmhNOjR|MkW0OlE>
TCC-SUP NYnSfZNpS2WubDDWbYFjcWyrdImgRZN{[Xl? MYCxMVExKM7:TR?= NWLTS3ZlPzJiaB?= MlrmbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> MWCyOFMzPTR4MR?=
RT4 NGHlcFRE\WyuIG\pZYJqdGm2eTDBd5NigQ>? M4HSNFEuOTBizszN NEDDR2c4OiCq MlnVbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> M2\HfVI1OzJ3NE[x
HONE1 MojwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGLWTpYxNjFvMUCg{txO M4Lob|Q5yqCq NF6ydmNqdmS3Y3XzJGczN01iZHXsZZkhcW5iYTDjc45k\W62cnH0bY9vNWSncHXu[IVvfCCvYX7u[ZI> NHnFfIMzPDJ|OEC5OC=>
HNE1 NFLVb3ZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWewMlEuOTBizszN M3rjR|Q5yqCq NYTNPIxHcW6mdXPld{BIOi:PIHTlcIF6KGmwIHGgZ49v[2WwdILheIlwdi2mZYDlcoRmdnRibXHucoVz M3\6R|I1OjN6MEm0
CNE2  M1[0Smdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWHQWXZ4OC5zLUGwJO69VQ>? MnvBOFjDqGh? M1f0O4lv\HWlZYOgS|IwVSCmZXzhfUBqdiCjIHPvcoNmdnS{YYTpc44u\GWyZX7k[Y51KG2jbn7ldi=> NFO4XmEzPDJ|OEC5OC=>
C666-1 MXPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1XsXVAvOS1zMDFOwG0> M1H6eVQ5yqCq NFPZZYtqdmS3Y3XzJGczN01iZHXsZZkhcW5iYTDjc45k\W62cnH0bY9vNWSncHXu[IVvfCCvYX7u[ZI> M3O5W|I1OjN6MEm0
HeLa MWnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MY[wMlEuOTBizszN M3vhXFI1KGh? MmXIbY5lfWOnczDHNk9OKGG{cnXzeEBqdiCjIHPvcoNmdnS{YYTpc44u\GWyZX7k[Y51KG2jbn7ldi=> MXSyOFI{QDB7NB?=
Hep3B NETK[|NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWewMlEuOTBizszN NF3iXJczPCCq NHHsR2VqdmS3Y3XzJGczyqCjcoLld5TDqA>? MnfpNlQzOzhyOUS=
HepG2 NXTOUId5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1rLc|Q5KGh? NIq4XnJKSzVyPUKuO|I4KMLzIECuOFI6KM7:TR?= M3KySlI{PTR4NUmx
Hep3B NFvtTnNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmPyOFghcA>? Mm\wTWM2OD12LkKyN{DDuSByLkizPUDPxE1? NE[1dowzOzV2NkW5NS=>
PLC/PRF5 NYrlfnBsT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlPZOFghcA>? MlO0TWM2OD1zNj6xNlAhyrFiND6wNFEh|ryP MkLSNlM2PDZ3OUG=
Huh7 MmfNS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlXUOFghcA>? NHXFXppKSzVyPUG1MlAxPyEEsTC3MlM{PCEQvF2= NEX0b3IzOzV2NkW5NS=>
HepG2 MUfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MoDGO|IhcA>? NH75R|BKSzVyPUGuNlAxKMLzIECuNlI3KM7:TR?= NIDifXozOzV2NkW5NS=>
Hep3B NGX0W21Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NF7BSm44OiCq Moj2TWM2OD1yLki5NkDDuSByLkC0OEDPxE1? MYmyN|U1PjV7MR?=
PLC/PRF5 M2fhT2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUm3NkBp MkTHTWM2OD1|LkGxNEDDuSByLkOzO{DPxE1? NYT0dYpVOjN3NE[1PVE>
Huh7 MmjQS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWDnVZQxPzJiaB?= MmTGTWM2OD1|Lkm4NEDDuSByLkiwN{DPxE1? MYmyN|U1PjV7MR?=
MFE280 MmXnS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYHJR|UxRTBwNEKgxtEhOC5yNjFOwG0> NXvIdpV4OjN2NEO4NFU>
AN3CA NXzTNZR[T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXrDR|Y{UUN3ME2wMlUxKMLzIECuNVAh|ryP NX;UfnZ6OjN2NEO4NFU>
HEC155 NVz5colJT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3KwZWlEPTB;MD62OkDDuSByLkC5JO69VQ>? MoDDNlM1PDN6MEW=
MFE296 M4DVZmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NX[xTGpCUUN3ME2wMlY3KMLzIECuNVkh|ryP NGTxfVkzOzR2M{iwOS=>
SPAC1S NXX1NZJ1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2nkfmlEPTB;MD63O{DDuSByLkC4JO69VQ>? MoLRNlM1PDN6MEW=
RL952 NWLXeI9nT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGH2XXZKSzVyPUCuPVMhyrFiMD6wNUDPxE1? M1jFcVI{PDR|OEC1
EN1 NUfhVG5kT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGDUOXFKSzVyPUGuNFIhyrFiMD6yOUDPxE1? M4PhXVI{PDR|OEC1
SNGII NFPNbY9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWXJR|UxRTFwMkSgxtEhOC5{ODFOwG0> MVmyN|Q1OzhyNR?=
ISHIKAWA NUK4b5hqT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYf4Xo9SUUN3ME2xMlMxKMLzIECuNVEh|ryP NYnOdYU3OjN2NEO4NFU>
HEC1A MWfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MluwTWM2OD1zLkO0JOKyKDBwM{Cg{txO MYeyN|Q1OzhyNR?=
KLE MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVrJR|UxRTFwM{egxtEhOC5yMjFOwG0> MojMNlM1PDN6MEW=
SNGM MnTVS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2XZRmlEPTB;MT60NkDDuSByLkGzJO69VQ>? M3TjUlI{PDR|OEC1
USPC2 M2XZWGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVXnXVg{UUN3ME2xMlYzKMLzIECuNFEh|ryP MnTaNlM1PDN6MEW=
EN NH;GOJZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3f0OWlEPTB;MT62OkDDuSByLkCxJO69VQ>? M{i3PVI{PDR|OEC1
MFE319 M2riXWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYruTpNrUUN3ME2xMlg4KMLzIECuOFUh|ryP M17hTFI{PDR|OEC1
EFE184 NWf5UYFST3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXPJR|UxRTJwMESgxtEhOC5zMzFOwG0> MU[yN|Q1OzhyNR?=
ECC1 Mnv3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHP1SIpKSzVyPUKuNFchyrFiMD6wNUDPxE1? MV2yN|Q1OzhyNR?=
HEC1B NXWzNGdlT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4e4PGlEPTB;Mj61O{DDuSByLkKzJO69VQ>? MkDXNlM1PDN6MEW=
USPC1 M4\M[Wdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWLJR|UxRTJwNkCgxtEhOC5zMzFOwG0> NUnqUmdPOjN2NEO4NFU>
SPAC1L NWfFNnF5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MoHPTWM2OD1|LkC2JOKyKDFwMUSg{txO MkXUNlM1PDN6MEW=
HUVEC NV62PXl6S2WubDDWbYFjcWyrdImgRZN{[Xl? MX:wMVI2KM7:TR?= Mn2wO|IhcA>? M3XjXWROW09? NWG5[4RicW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? MmjCNlMzOjhyMUe=
HMVEC M4DvNmNmdGxiVnnhZoltcXS7IFHzd4F6 M13DZlAuOjVizszN MmDUO|IhcA>? MYPEUXNQ MXPpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> NEmxbIQzOzJ{OECxOy=>
MHCC-97H MXjD[YxtKF[rYXLpcIl1gSCDc4PhfS=> NHTmTHkxNTJ3IN88US=> NIPEUY84OiCq NFvvRW5FVVOR NYLmToducW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? M1fPWFI{OjJ6MEG3
SMMC7721 Mnf5R4VtdCCYaXHibYxqfHliQYPzZZk> M{HBSFAuOjVizszN MkfHO|IhcA>? NVy0dnpvTE2VTx?= NXjrXpZHcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? MYqyN|IzQDBzNx?=
Huh-7 MWrBdI9xfG:|aYOgRZN{[Xl? NWi2N2lLOC1zMj61JO69VQ>? NF7nN5AzPCCq M{WyTGROW00EoB?= MXrz[Y5{cXSrenXzJGhESyClZXzsd{B1dyCWUlHJUE0h[W6mIITp[4F1fXq3bXHiMYlv\HWlZXSgZZBweHSxc3nzJIlvKGFiZH;z[U1l\XCnbnTlcpQhdWGwbnXy MoTwNlIzOzB2N{m=
Sk-Hep1 MXjBdI9xfG:|aYOgRZN{[Xl? MmP6NE0yOi53IN88US=> M1\hdVI1KGh? MWPEUXNQyqB? NX[0PIhSe2Wwc3n0bZpmeyCKQ1OgZ4VtdHNidH:gWHJCUUxvIHHu[EB1cWejdIX6eY1i[i2rbnT1Z4VlKGGyb4D0c5NqeyCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5meg>? NWTXXI5wOjJ{M{C0O|k>
Hep3B M1rj[GFxd3C2b4Ppd{BCe3OjeR?= NE\KWmUxNTF{LkWg{txO MX:yOEBp MmK5SG1UV8Li MYnz[Y5{cXSrenXzJGhESyClZXzsd{B1dyCWUlHJUE0h[W6mIITp[4F1fXq3bXHiMYlv\HWlZXSgZZBweHSxc3nzJIlvKGFiZH;z[U1l\XCnbnTlcpQhdWGwbnXy MkDzNlIzOzB2N{m=
PLC5 NGrkbHlCeG:ydH;zbZMhSXO|YYm= M37pVlAuOTJwNTFOwG0> NHvxdo4zPCCq NHLTbWxFVVORwrC= NHXaTmt{\W6|aYTpfoV{KEiFQzDj[YxteyC2bzDUVmFKVC1iYX7kJJRq\2G2dYr1cYFjNWmwZIXj[YQh[XCxcITvd4l{KGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVz Mm[zNlIzOzB2N{m=
PLC5 M1HwT2NmdGxiVnnhZoltcXS7IFHzd4F6 MnP3NE0yPSEQvF2= NIPNWo04OiCq NFi4UFJz\WS3Y3XzJINmdGxidnnhZoltcXS7IHnuJIEh\G:|ZT3k[ZBmdmSnboSgcYFvdmW{wrC= NV7OfYZkOjJzOECzNFg>
Hep3B NIG1WWNE\WyuIG\pZYJqdGm2eTDBd5NigQ>? MnrBNE0yPSEQvF2= NXvpWHlmPzJiaB?= MYPy[YR2[2W|IHPlcIwhfmmjYnnsbZR6KGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVzyqB? NUnZRoV1OjJzOECzNFg>
Sk-Hep1 Ml\XR4VtdCCYaXHibYxqfHliQYPzZZk> M{fwflAuOTVizszN NGfudZc4OiCq Ml7rdoVlfWOnczDj[YxtKH[rYXLpcIl1gSCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5mesLi NGT0boUzOjF6MEOwPC=>
Huh-7 Ml;1R4VtdCCYaXHibYxqfHliQYPzZZk> MWOwMVE2KM7:TR?= M3jUN|czKGh? NXLEPGx4emWmdXPld{Bk\WyuII\pZYJqdGm2eTDpckBiKGSxc3Wt[IVx\W6mZX70JI1idm6nctMg NEjuWnczOjF6MEOwPC=>
PLC5 M4TOO2Fxd3C2b4Ppd{BCe3OjeR?= Mmm3NE0yPSEQvF2= M3fEXlI1KGh? MVTpcoNz\WG|ZYOgZZBweHSxdHnjJINmdGxiZHXheIghcW5iYTDkc5NmNWSncHXu[IVvfCCvYX7u[ZLDqA>? MmDmNlIyQDB|MEi=
Hep3B NXfrOJZxSXCxcITvd4l{KEG|c3H5 MXuwMVE2KM7:TR?= NHLQNlEzPCCq NWXKRZQ{cW6lcnXhd4V{KGGyb4D0c5Rq[yClZXzsJIRm[XSqIHnuJIEh\G:|ZT3k[ZBmdmSnboSgcYFvdmW{wrC= NECySGwzOjF6MEOwPC=>
Sk-Hep1 NIfublhCeG:ydH;zbZMhSXO|YYm= M4nudFAuOTVizszN MXKyOEBp Mo[xbY5kemWjc3XzJIFxd3C2b4TpZ{Bk\WyuIHTlZZRpKGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVzyqB? M2fDW|IzOThyM{C4
Huh-7 NYPWXXl[SXCxcITvd4l{KEG|c3H5 NHPpeIwxNTF3IN88US=> MV6yOEBp NHOyboJqdmO{ZXHz[ZMh[XCxcITveIlkKGOnbHyg[IVifGhiaX6gZUBld3OnLXTldIVv\GWwdDDtZY5v\XMEoB?= MorTNlIyQDB|MEi=
PLC5 NX3uZWI3TnWwY4Tpc44hSXO|YYm= Ml;kNE0yOCEQvF2= NILxSnczPCCq MVzjZZV{\XNiZH;z[U1l\XCnbnTlcpQhTE6DIH\yZYdu\W62YYTpc44> NGW3SJYzOjF6MEOwPC=>
Hep3B M3K4c2Z2dmO2aX;uJGF{e2G7 MlSzNE0yOCEQvF2= Mn30NlQhcA>? NH3oNnVk[XW|ZYOg[I9{\S2mZYDlcoRmdnRiRF7BJIZz[WevZX70ZZRqd25? MXSyNlE5ODNyOB?=
Sk-Hep1 NVH5TZZCTnWwY4Tpc44hSXO|YYm= NXXS[4xLOC1zMDFOwG0> M1XJUFI1KGh? MWnjZZV{\XNiZH;z[U1l\XCnbnTlcpQhTE6DIH\yZYdu\W62YYTpc44> M13ud|IzOThyM{C4
Huh-7 M2HHd2Z2dmO2aX;uJGF{e2G7 MkW0NE0yOCEQvF2= Ml\JNlQhcA>? NUHRZZc5[2G3c3XzJIRwe2VvZHXw[Y5l\W62IFTORUBnemGpbXXueIF1cW:w MmfhNlIyQDB|MEi=
SW780 NXPxe4xNT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnnYOUBl MkjqTWM2OD13MDDuUS=> NG\rcoczOTFzOU[2NS=>
RT112 MXfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NF\mTXI2KGR? M{S1cmlEPTB;MUWgcm0> M{HB[VIyOTF7Nk[x
RT4 M{nDRWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWK1JIQ> MkCyTWM2OD13IH7N NFOyb5gzOTFzOU[2NS=>
JMSU1 M17lSmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NV;NeVU4PSCm M1vJWGlEPTB;NUCgcm0> MmPzNlEyOTl4NkG=
J82 NGiyPZFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHzJ[nI2KGR? NFLENZNKSzVyPUG0NFAhdk1? NVGyZlJLOjFzMUm2OlE>
97-7 NIWxU2dIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1PIdFUh\A>? M3[xemlEPTB;MUCwNEBvVQ>? NUXhO4tbOjFzMUm2OlE>
RT112 MmXuSpVv[3Srb36gRZN{[Xl? M3v4[VUxOCCwTR?= NW[3W3RSOjRiaB?= MlzWbY5kemWjc3XzJJRp\SCycn;wc5J1cW:wIH;mJINmdGy|IHnuJGcyyqCjY3PvcZBidmmnZDDifUBiKGSnY4LlZZNmKGmwIGOgZY5lKEd{L12gdIhie2W| NFvTeI0zOTFzOU[2NS=>
RT4 MUHGeY5kfGmxbjDBd5NigQ>? M4nkXlUxOCCwTR?= NVGxNWVROjRiaB?= M3THTolv[3KnYYPld{B1cGVicILvdI9zfGmxbjDv[kBk\WyuczDpckBIOcLiYXPjc41x[W6rZXSgZpkh[SCmZXPy[YF{\SCrbjDTJIFv\CCJMj;NJJBp[XOncx?= M2DmNVIyOTF7Nk[x
MGH-U3 NVXlWWRiTnWwY4Tpc44hSXO|YYm= MnXDOVAxKG6P M4HaXVI1KGh? NFzYVWpqdmO{ZXHz[ZMhfGinIIDyc5BwenSrb36gc4Yh[2WubIOgbY4hTzIEoHHjZ49ueGGwaXXkJIJ6KGFiZHXjdoVie2ViaX6gV{BidmRiR{KvUUBxcGG|ZYO= NVvHNm5yOjFzMUm2OlE>
SW780 M4\ySWZ2dmO2aX;uJGF{e2G7 MoPhOVAxKG6P M{X3fFI1KGh? MUXpcoNz\WG|ZYOgeIhmKHC{b4DvdpRqd25ib3[gZ4VtdHNiaX6gS|HDqGGlY3;tdIFvcWWmIHL5JIEh\GWlcnXhd4UhcW5iUzDhcoQhTzJxTTDwbIF{\XN? MnzlNlEyOTl4NkG=
97-7 MlzBSpVv[3Srb36gRZN{[Xl? NInxU|Y2ODBibl2= M4[yU|I1KGh? NUnKb2dKcW6lcnXhd4V{KHSqZTDwdo9xd3K2aX;uJI9nKGOnbHzzJIlvKEdzwrDhZ4NwdXCjbnnl[EBjgSCjIHTlZ5Jm[XOnIHnuJHMh[W6mIFeyM20heGijc3Xz NVy5cJQ{OjFzMUm2OlE>
 J807C M3\6ZWNmdGxiVnnhZoltcXS7IFHzd4F6 MYOwMVQxOCCwTR?= Ml\kOFghcA>? NHjk[2pqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? M1LOVFE2PTl6OEG0
Y373C MVjD[YxtKF[rYXLpcIl1gSCDc4PhfS=> M2HReVAuPDByIH7N MoHIOFghcA>? NHXjT2tqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? M135b|E2PTl6OEG0
K650E NVfGd4NlS2WubDDWbYFjcWyrdImgRZN{[Xl? MVGwMVQxOCCwTR?= MX:0PEBp NH\DbWxqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? MoPSNVU2QTh6MUS=
G384D MYPD[YxtKF[rYXLpcIl1gSCDc4PhfS=> NFewXoIxNTRyMDDuUS=> MUO0PEBp MoH6bY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> MlLGNVU2QTh6MUS=
F384L NYLMSZlnS2WubDDWbYFjcWyrdImgRZN{[Xl? MYSwMVQxOCCwTR?= M1PTTlQ5KGh? NFnQ[WZqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? NYnyTXhKOTV3OUi4NVQ>
KMS11 NFriPINIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIDS[oE4OiCq Mo\sTWM2OD17MDDuUS=> MVqxOVU6QDhzNB?=
KMS18 NWLybVRQT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYq3NkBp M1viWGlEPTB;NUWwJI5O MnrkNVU2QTh6MUS=
OPM2 NWfTcotWT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVO3NkBp MUTJR|UxRTlyIH7N Ml\6NVU2QTh6MUS=
H929 NUnIN2tGT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWW3NkBp M{\JUWlEPTB-IEK1NFAhdk1? M{GwRVE2PTl6OEG0
8226 Mn25S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUe3NkBp NHf2e4lKSzVyPjCyOVAxKG6P MWixOVU6QDhzNB?=
U266 NIH1cIRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MW[3NkBp NUPLUpVwUUN3ME6gNlUxOCCwTR?= MUCxOVU6QDhzNB?=

... 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]
+ Expand

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]
+ Expand
  • 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]
+ Expand
  • Animal Models: 8-week-old female BNX mice bearing KMS11 cells
  • Formulation: 5 mM citrate buffer
  • 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 N/A

Bio Calculators

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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
NCT01030055 Completed Drug: TKI258 (dovitinib) Neoplasms|Cancer|Tumors Novartis Pharmaceuticals|Novartis February 2010 Phase 1

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID