Multi-kinase-IN-2

Multi-kinase-IN-2 (compound 7h) is an orally active and potent angiokinase inhibitor. Multi-kinase-IN-2 exhibits excellent inhibitory activity against angiokinases including VEGFR-1/2/3, PDGFRα/β, and FGFR-1, as well as LYN and c-KIT kinases. Multi-kinase-IN-2 significantly attenuates phosphorylation of AKT and ERK proteins. Multi-kinase-IN-2 induces cell apoptosis. Multi-kinase-IN-2 shows anticancer activity[1].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> PDGFR

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> Src

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> FGFR

Signaling Pathways >> PI3K/Akt/mTOR >> Akt

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> VEGFR

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> c-Kit

VEGFR-3:6.3 ± 0.5 nM (IC50)

VEGFR-2:6.5 ± 0.9 nM (IC50)

VEGFR-1:31 ± 2.1 nM (IC50)

PDGFRα:7.0 ± 0.1 nM (IC50)

PDGFRβ:9.9 ± 0.7 nM (IC50)

FGFR1:23 ± 2.5 nM (IC50)

pAKT

Multi-kinase-IN-2 (compound 7h) (0-10 μM, 14 days) potently inhibits colony formation of HT-29, MKN74, and HepG2 cancer cells[1]. Multi-kinase-IN-2 (0-3 μM, 24 h) significantly attenuates phosphorylation of AKT and ERK proteins[1]. Multi-kinase-IN-2 (0-3 μM, 72 h) induces apoptosis of HT-29, MKN74, and HepG2 cell[1]. Cell Proliferation Assay[1] Cell Line: HT-29, HepG2, and MKN74 cells Concentration: 0, 0.2, 0.5, 1, and 2 μM or 0, 0.3, 1, 3, and 10 μM Incubation Time: 14 days Result: Exhibited excellent activity in inhibition of colony formations in a dose-dependent manner, with remarkable activity at 1 µM concentration. Western Blot Analysis[1] Cell Line: HT-29 and HepG2 Concentration: 0, 0.2, 0.5, 1, and 2 μM or 0, 0.3, 1, 3, and 10 μM Incubation Time: 24 h Result: Suppressed the phosphorylation of AKT (Ser473) in a dose-dependent manner with a significant inhibition of ERK (Thr202/Tyr204) phosphorylation at 3 μM. Apoptosis Analysis[1] Cell Line: HT-29, MKN74, and HepG2 cells Concentration: 0, 0.3, 1, and 3 μM Incubation Time: 72 h Result: Triggered severe apoptosis of HT-29, MKN74, and HepG2 cells in a dose-dependent manner.

Multi-kinase-IN-2 (compound 7h) (100 mg/kg, Orally, once daily for 18 days) displays mild inhibition of tumor growth in mice[1]. Animal Model: Female nu/nu mice (4-6 weeks old, HT-29 human colon cancer xenograft model)[1] Dosage: 100 mg/kg Administration: Orally, once daily for 18 days Result: Displayed mild inhibition of tumor growth, with tumor growth inhibition (TGI) value of 13.39%.

[1]. Qin M, et al. Structural modifications of indolinones bearing a pyrrole moiety and discovery of a multi-kinase inhibitor with potent antitumor activity. Bioorg Med Chem. 2020 Jun 1;28(11):115486.