Cofttek holdings limited

PDGFR&FGFR

Dovitinib (TKI-258) (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.

Not Intended for Therapeutic Use. For research use only.

CAS: 405169-16-6 Category

Dovitinib (TKI-258) (405169-16-6) Description:

Dovitinib (TKI-258, CHIR-258) is a benzimidazole-quinolinone compound and receptor tyrosine kinase (RTK) inhibitor with potential antineoplastic activity. Dovitinib binds to and inhibits the phosphorylation of type III-V RTKs, such as vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) that promote tumor cell proliferation and survival in certain cancer cells. In addition, this agent also inhibits other members of the RTK superfamily, including fibroblast growth factor receptor 1 and 3, FMS-like tyrosine kinase 3, stem cell factor receptor (c-KIT), and colony stimulating factor receptor 1. This may further lead to a reduction of cellular proliferation and angiogenesis, and an induction of tumor cell apoptosis.

Dovitinib (TKI-258, CHIR-258) 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.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.

Dovitinib (TKI-258) (405169-16-6) Specifications:

Product Name Dovitinib (TKI-258, CHIR-258)
Synonym TKI258; TKI-258; TKI 258; CHIR258; CHIR-258; CHIR 258; Dovitinib lactate
Chemical Name 4-Amino-5-fluoro-3-[6-(4-methyl-1-piperazinyl)-1H-benzimidazol-2-yl]-2(1H)-quinolinon
Purity ≥98% (HPLC)
CAS Number 405169-16-6
Molecular Formula C21H21FN6O
Molecular Weight 392.438 g/mol
Monoisotopic Mass 392.176 g/mol
MDL number MFCD10565680
InChIKey PIQCTGMSNWUMAF-UHFFFAOYSA-N
InChi Code InChI=1S/C21H21FN6O/c1-27-7-9-28(10-8-27)12-5-6-14-16(11-12)25-20(24-14)18-19(23)17-13(22)3-2-4-15(17)26-21(18)29/h2-6,11H,7-10H2,1H3,(H,24,25)(H3,23,26,29)
SMILES O=C1NC2=C(C(F)=CC=C2)C(N)=C1C3=NC4=CC=C(N5CCN(C)CC5)C=C4N3

 

Form Powder
Color Yellow-green powder
Solubility  DMSO 40 mg/mL (101.93 mM)

Water Insoluble

Alcohol Insoluble

Storage Temp.  -20°C
Shelf life >2 years if stored properly
Handling Protect from air and moisture
Application a benzimidazole-quinolinone compound and receptor tyrosine kinase (RTK) inhibitor with potential antineoplastic activity

 


=

RIDADR NONH for all modes of transport

References:

[1]. Cheng AL, Thongprasert S, Lim HY, Sukeepaisarnjaroen W, Yang TS, Wu CC, Chao Y, Chan SL, Kudo M, Ikeda M, Kang YK, Pan H, Numata K, Han G, Balsara B, Zhang Y, Rodriguez AM, Zhang Y, Wang Y, Poon RT. Randomized, open-label phase 2 study comparing frontline dovitinib versus sorafenib in patients with advanced hepatocellular carcinoma. Hepatology. 2016 Sep;64(3):774-84. doi: 10.1002/hep.28600. Epub 2016 May 17. PubMed PMID: 27082062.

[2]. A Phase Ib Study of the FGFR/VEGFR Inhibitor Dovitinib With Gemcitabine and Capecitabine in Advanced Solid Tumor and Pancreatic Cancer Patients. Ma WW, Xie H, Fetterly G, Pitzonka L, Whitworth A, LeVea C, Wilton J, Mantione K, Schihl S, Dy GK, Boland P, Iyer R, Tan W, Brady W, Straubinger RM, Adjei AA.Am J Clin Oncol. 2018 Nov 8. doi: 10.1097/COC.0000000000000492. [Epub ahead of print] PMID: 30418178

[3]. Pilot study of dovitinib in patients with von Hippel-Lindau disease. Pilié P, Hasanov E, Matin SF, Woodson AHH, Marcott VD, Bird S, Slack RS, Fuller GN, McCutcheon IE, Jonasch E.Oncotarget. 2018 May 4;9(34):23390-23395. doi: 10.18632/oncotarget.25171. eCollection 2018 May 4.PMID: 29805741

[4]. Schäfer N, Gielen GH, Kebir S, Wieland A, Till A, Mack F, Schaub C, Tzaridis T, Reinartz R, Niessen M, Fimmers R, Simon M, Coch C, Fuhrmann C, Herrlinger U, Scheffler B, Glas M. Phase I trial of dovitinib (TKI258) in recurrent glioblastoma. J Cancer Res Clin Oncol. 2016 Jul;142(7):1581-9. doi: 10.1007/s00432-016-2161-0. Epub 2016 Apr 21. PubMed PMID: 27100354.

[5]. Yadav SS, Li J, Stockert JA, Herzog B, O’Connor J, Garzon-Manco L, Parsons R, Tewari AK, Yadav KK. Induction of Neuroendocrine Differentiation in Prostate Cancer Cells by Dovitinib (TKI-258) and its Therapeutic Implications. Transl Oncol. 2017 Jun;10(3):357-366. doi: 10.1016/j.tranon.2017.01.011. Epub 2017 Mar 24. PubMed PMID: 28342996; PubMed Central PMCID: PMC5369368

1 review for Dovitinib (TKI-258) (405169-16-6)

  1. Rated 5 out of 5

    Cofttek

    Never had such good experience before,The Dovitinib (TKI-258) (405169-16-6) is high purity,also customer service is pretty nice !gotta try!!

Add a review

Your email address will not be published. Required fields are marked *