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Sitravatinib malate

Names

[ CAS No. ]:
2244864-88-6

[ Name ]:
Sitravatinib malate

Biological Activity

[Description]:

Sitravatinib malate (MGCD516 malate) is an orally bioavailable receptor tyrosine kinase (RTK) inhibitor with IC50s of 1.5 nM, 2 nM, 2 nM, 5 nM, 6 nM, 6 nM, 8 nM, 0.5 nM, 29 nM, 5 nM, and 9 nM for Axl, MER, VEGFR3, VEGFR2, VEGFR1, KIT, FLT3, DDR2, DDR1, TRKA, TRKB, respectively[1]. Sitravatinib malate shows potent single-agent antitumor efficacy and enhances the activity of PD-1 blockade through promoting an antitumor immune microenvironment[2].

[Related Catalog]:

Research Areas >> Cancer
Signaling Pathways >> Protein Tyrosine Kinase/RTK >> FLT3
Research Areas >> Inflammation/Immunology
Signaling Pathways >> Protein Tyrosine Kinase/RTK >> Trk Receptor
Signaling Pathways >> Protein Tyrosine Kinase/RTK >> VEGFR
Signaling Pathways >> Protein Tyrosine Kinase/RTK >> c-Kit
Signaling Pathways >> Protein Tyrosine Kinase/RTK >> Discoidin Domain Receptor

[Target]

Axl:1.5 nM (IC50)

MER:2 nM (IC50)

VEGFR3:2 nM (IC50)

VEGFR2:5 nM (IC50)

VEGFR1:6 nM (IC50)

TrkA:5 nM (IC50)

TrkB:9 nM (IC50)

KIT:6 nM (IC50)

FLT3:8 nM (IC50)

DDR2:0.5 nM (IC50)

DDR1:29 nM (IC50)


[In Vitro]

Sitravatinib (0.01 nM-10 μM; 14 days) reduces colony formation in a dose-dependent manner in KLN205 and E0771 cell lines[2]. Sitravatinib (0.001-10 μM; 5 days) inhibits tumor cell viability with IC50s of approximately 1 μM in KLN205, E0771 and CT1B-A5 cell lines[2]. Cell Viability Assay[2] Cell Line: KLN205, E0771, CT1B-A5 cells Concentration: 0.001, 0.01, 0.1, 1, 10 μM Incubation Time: 5 days Result: Inhibited KLN205, E0771, CT1B-A5 cells with IC50s of approximately 1 μM.

[In Vivo]

Sitravatinib (20 mg/kg; p.o.; once per day for 6 days) significantly inhibits tumor progression and induces tumor regression in C57BL/6 mice bearing CT1B-A5 cells model[2]. Animal Model: 6-week-old C57BL/6 mice (bearing CT1B-A5 cells)[2] Dosage: 20 mg/kg Administration: Oral administration; once per day for 6 days Result: Significantly inhibited tumor progression and induced tumor regression.

[References]

[1]. Patwardhan PP et al. Significant blockade of multiple receptor tyrosine kinases by MGCD516 (Sitravatinib), a novel small molecule inhibitor, shows potent anti-tumor activity in preclinical models of sarcoma. Oncotarget, 2016 Jan 26;7(4):4093-109.

[2]. Du W, et al. Sitravatinib potentiates immune checkpoint blockade in refractory cancer models. JCI Insight. 2018 Nov 2;3(21). pii: 124184.

Chemical & Physical Properties

[ Molecular Formula ]:
C37H35F2N5O9S

[ Molecular Weight ]:
763.76


Related Compounds