Dovitinib lactate

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

一种新型多靶点 RTK III、IV 和 V 类 RTK 抑制剂。

A novel, multitargeted RTK inhibitor of class III, IV, and V RTKs with IC50 of 1/2/36/8/9 nM for FLT3/c-KIT/c-Fms/FGFR1/FGFR3, respectively; also inhibits VEGFR1/2/3 (IC50=10/13/8 nM) and PDGFRβ/α (IC50=27/210 nM); selectively inhibits the growth of B9 cells and human myeloma cell lines expressing wild-type (WT) or activated mutant FGFR3; inhibits downstream ERK 1/2 phosphorylation and induces cytostatic and cytotoxic effects; demonstrates activity in a xenograft mouse model of FGFR3 MM; orally active.Blood Cancer Phase 2 Clinical.

Dovitinib potently inhibits the FGF-stimulated growth of WT and F384L-FGFR3-expressing B9 cells with IC50 values of 25 nM. 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 values of 90 nM (KMS11 and OPM2) and 550 nM, respectively. Treatment of SK-HEP1 cells with dovitinib results in G2/M cell cycle arrest, inhibition of colony formation in soft agar and blockade of bFGF-induced cell migration. Dovitinib inhibits basal expression and FGF-induced phosphorylation of FGFR-1, FRS2-α and ERK1/2.

Dovitinib (10 mg/kg, 30 mg/kg, 60 mg/kg, p.o.) shows significant antitumor effect in the KMS11-bearing mice model, and the growth inhibition is 48%, 78.5%, and 94% in the 10 mg/kg, 30 mg/kg, and 60 mg/kg treatment arms, respectively, compared with the placebo-treated mice. Dovitinib demonstrates significant antitumor and antimetastatic activities in HCC xenograft models. Dovitinib potently inhibits tumor growth of six HCC lines. Inhibition of angiogenesis correlates with inactivation of FGFR/PDGFR-β/VEGFR-2 signaling pathways. Dovitinib also causes dephosphorylation of retinoblastoma, upregulation of p-histone H2A-X and p27, and downregulation of p-cdk-2 and cyclin B1, which results in a reduction in cellular proliferation and the induction of tumor cell apoptosis.

CHIR-258 | TKI258 | TKI-258 | TKI 258 | CHIR258 | CHIR 258

Angiogenesis

FGFR

FGFR

Cancer

Blood cancer

692737-80-7

482.5073832

C24H27FN6O4

>98% (HPLC)

DMSO: ≥ 30 mg/mL

CC(C(=O)O)O.CN1CCN(CC1)C2=CC3=C(C=C2)N=C(N3)C4=C(C5=C(C=CC=C5F)NC4=O)N

Propanoic acid, 2-hydroxy-, compd. with 4-amino-5-fluoro-3-[6-(4-methyl-1-piperazinyl)-1H-benzimidazol-2-yl]-2(1H)-quinolinone (1:1)

(-20℃)

With Ice Pack

≥ 2 years