MGCD-265 analog (Glesatinib) is an orally bioavailable multitargeted tyrosine kinase inhibitor with potential antineoplastic activity with IC50 of 29 nM and 10 nM for c-Met and VEGFR2, respectively.

VEGFR2:10 nM, c-Met:29 nM

MGCD-265是一种多靶点受体酪氨酸激酶抑制剂，对Met, MetY1235D, MetM1250T, VEGFR1, VEGF2, VEGF3, Ron和Tie2显示出强效抑制作用，IC50值在1 nM至7 nM范围。[1] MGCD-265在c-Met驱动的肿瘤细胞（MKN45, MNNG-HOS, SNU-5）和非c-Met驱动的肿瘤细胞（HCT116和MDA-MB-231）中均能抑制细胞增殖，IC50值分别为6 nM–30 nM和1 μM–3 μM。在血清饥饿的MKN45细胞中，MGCD-265（40 nM–5 μM）有效抑制c-Met磷酸化及其下游信号通路，包括Erk, Akt, Stat3和Fak。MGCD-265（6 nM–1 μM）还能诱导MKN45细胞发生凋亡。

在c-Met驱动或非c-Met驱动的MKN45、U87 mg、MDA-MB-231、COLO205和A549肿瘤细胞小鼠异种移植模型中，MGCD-265（20 mg/kg–60 mg/kg）抑制肿瘤生长和c-Met信号传导。MGCD-265（40 mg/kg）还在带有U87 mg异种移植物的小鼠的肿瘤和血浆中下调与血管生成相关的基因表达，包括VEGF和IL-8。MGCD-265也抑制了shed-Met在血浆中的水平。

Time-resolved fluorescence resonance energy transfer assay: The c-Met–catalyzed phosphorylation of N-biotinylated peptide (EQEDEPEGDYFEWLE-CONH2) is measured using a time-resolved fluorescence resonance energy transfer assay. [2] The MK-2461 IC50 for Ron, Mer, Flt1, Flt3, Flt4, KDR, PDGFRβ, FGFR1, FGFR2, FGFR3, TrkA, and TrkB are determined using time-resolved fluorescence resonance energy transfer assays similar to the c-Met kinase assay.

Cells are treated with MGCD-265 for 72 hours and cell number is determined as a function of mitochondrial activity, following incubation with MTT for 4 hours.(Only for Reference)