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Description

Sitravatinib (MGCD516) is a receptor tyrosine kinases (RTK) inhibitor that blocks a wide array of RTKs known to be amplified/overexpressed in sarcomas, which are key regulators of signaling pathways that lead to cell growth, survival and tumor progression. It is involved in driving sarcoma cell growth with IC50 of 3980 nM and is superior to other multi-kinase inhibitors in inhibiting cell proliferation, RTK phosphorylation, and phosphorylation of downstream effectors. The efficacy of sitravatinib was tested using a wide panel of sarcoma cell lines, including malignant peripheral nerve sheath tumor (MPNST), Ewing sarcoma (A673), osteosarcoma (Saos2), and liposarcoma (DDLS, LS141). Both in vitro and in vivo efficacy sitravatinib was significantly better that the other two multi-kinase inhibitors, imatinib and crizotinib. Sitravatinib treatment not only inhibits tumor cell proliferation at low nanomolar concentrations in vitro but also results significant tumor growth suppression in vivo in mouse xenograft models. Sitravatinib is being evaluated in a Phase 1b dose expansion cohort in selected patients with specific genetic alterations that are drivers of tumor growth, with an initial focus on Non-Small-Cell Lung carcinoma (NSCLC) and in other solid tumors where sitravatinib may confer a benefit. Its efficacy and safety is also being tested in Phase II clinical trials in patients with advanced liposarcoma as a monotherapy and NSCLC in combination with nivolumab.

Approval Year

PubMed

PubMed

TitleDatePubMed
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.
2016 Jan 26
Patents

Sample Use Guides

In Vivo Use Guide
Administered at 150 mg orally, daily, in continuous 21 day cycles
Route of Administration: Oral
In Vitro Use Guide
Malignant peripheral nerve sheath tumor (MPNST, ST8814), Ewing sarcoma (CHP100, A673), Dedifferentiated liposarcoma (LS141, DDLS) and Synovial sarcoma (SYO-1 and HSSY-II) cell lines were used for activity evaluation. 2,000–3,000 cells were plated in 96-well plates in RPMI/DME media with 10% FBS and then treated with MG-516. After 72 hours, media was replaced with 100 μL of media with 10% serum and 10% CCK-8 solution (Dojindo Molecular Technologies Kit). After 1 hour, the optical density was read at 450 nm using a Spectra Max 340 PC (Molecular Devices Corp.) to determine viability
Substance Class
Concept
Record UNII
ZR2110H6XE
Record Status Validated (UNII)
Record Version
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Name Type Language
SITRAVATINIB MALATE
USAN  
Official Name English
MGCD516 MALATE SALT
Code English
SITRAVATINIB L-MALATE
Common Name English
N-(3-FLUORO-4-(2-(5-((2-METHOXYETHYLAMINO) METHYL) PYRIDIN-2-YL) THIENO (3,2-B) PYRIDIN- 7-YLOXY) PHENYL)-N-(4-FLUOROPHENYL) CYCLOPROPANE-1,1-DICARBOXAMIDE , L-MALATE SALT
Systematic Name English
N-(3-FLUORO-4-((2-(5-(((2-METHOXYETHYL)AMINO)METHYL)PYRIDIN-2-YL)THIENO(3,2-B)PYRIDIN-7-YL)OXY)PHENYL)-N'-(4-FLUOROPHENYL)CYCLOPROPANE-1,1-DICARBOXAMIDE (2S)-2-HYDROXYBUTANEDIOATE (1:1)
Common Name English
SITRAVATINIB MALATE [USAN]
Common Name English
BUTANEDIOIC ACID, 2-HYDROXY-, (2S)-, COMPD. WITH N-(3-FLUORO-4-((2-(5-(((2-METHOXYETHYL)AMINO)METHYL)-2-PYRIDINYL)THIENO(3,2-B)PYRIDIN-7-YL)OXY)PHENYL)-N'-(4-FLUOROPHENYL)-1,1-CYCLOPROPANEDICARBOXAMIDE (1:1)
Common Name English
MGCD-516 MALATE SALT
Code English
MGCD-516 L-MALATE
Code English
This is a non-substance concept
Related Record Type Details
ACTIVE MOIETY
This is a non-substance concept