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Glesatinib

Names

[ CAS No. ]:
936694-12-1

[ Name ]:
Glesatinib

[Synonym ]:
UNII:7Q29OXD98N
7Q29OXD98N
N-[(3-Fluoro-4-{[2-(5-{[(2-methoxyethyl)amino]methyl}-2-pyridinyl)thieno[3,2-b]pyridin-7-yl]oxy}phenyl)carbamothioyl]-2-(4-fluorophenyl)acetamide
Benzeneacetamide, 4-fluoro-N-[[[3-fluoro-4-[[2-[5-[[(2-methoxyethyl)amino]methyl]-2-pyridinyl]thieno[3,2-b]pyridin-7-yl]oxy]phenyl]amino]thioxomethyl]-
Glesatinib

Biological Activity

[Description]:

Glesatinib (MGCD265) is an orally active, potent MET/SMO dual inhibitor. Glesatinib, a tyrosine kinase inhibitor, antagonizes P-glycoprotein (P-gp) mediated multidrug resistance (MDR) in non-small cell lung cancer (NSCLC)[1][2].

[Related Catalog]:

Research Areas >> Cancer
Signaling Pathways >> Protein Tyrosine Kinase/RTK >> TAM Receptor
Signaling Pathways >> Protein Tyrosine Kinase/RTK >> c-Met/HGFR

[Target]

MET


[In Vitro]

Glesatinib (MGCD265; 0.01-5 μM; for 72 hours) results in a dose-dependent inhibition of cancer cell growth and shows the low IC50 value of 0.08 μM on NSCLC H1299 cells[1]. Glesatinib (0.01, 0.1, 0.5, 1 μM) significantly increases by several-fold the percentage of apoptotic cells in NSCLC H1299 cells[1]. Glesatinib has the cytotoxicity to P-gp overexpressing cancer cells KB-C2, SW620/Ad300, HEK293/ABCB1, and their parent cells KB-3-1, SW620, HEK293 cells with the IC50s fell between 5 and 10 μM[1]. Glesatinib (1, 3 μM; 120 mins) increases the intracellular [3H]-Paclitaxel accumulation and inhibits [3H]-Paclitaxel efflux in cancer cell lines overexpressing P-gp[2]. Glesatinib (0-40 μM) stimulates the ATPase activity of P-gp transporters in a dose-dependent manner[2]. Cell Proliferation Assay[1] Cell Line: NSCLC H1299 cells Concentration: 0.01, 0.1, 1, 2, 5 μM Incubation Time: For 72 hours Result: Resulted in a dose-dependent inhibition of cancer cell growth and showed the lowest IC50 value of 0.08 μM.

[In Vivo]

Glesatinib (MGCD265; 15 mg/kg/day; orally; 40 weeks) causes a significant decrease in tumor size[1]. Animal Model: 4−6-week old female balb/c athymic (nu/nu) mice with HCC827 NSCLC tumor xenografts[1] Dosage: 15 mg/kg Administration: Orally; daily; 40 weeks Result: Caused a significant decrease in tumor size.

[References]

[1]. Morgillo F, et al. Dual MET and SMO Negative Modulators Overcome Resistance to EGFR Inhibitors in Human Nonsmall Cell Lung Cancer. J Med Chem. 2017 Sep 14;60(17):7447-7458.

[2]. Cui Q, et al. Glesatinib, a c-MET/SMO Dual Inhibitor, Antagonizes P-glycoprotein Mediated MultidrugResistance in Cancer Cells. Front Oncol. 2019 Apr 25;9:313.

Chemical & Physical Properties

[ Density]:
1.4±0.1 g/cm3

[ Molecular Formula ]:
C31H27F2N5O3S2

[ Molecular Weight ]:
619.705

[ Exact Mass ]:
619.152344

[ LogP ]:
6.50

[ Index of Refraction ]:
1.672

Related Compounds