Sitravatinib

SKU: orb1302929

Description

Sitravatinib (MGCD516) is a multi-targeted receptor tyrosine kinase (RTK) inhibitor active against key drivers in sarcoma, such as c-Met, Axl, and PDGFR family members. It has demonstrated anti-proliferative and anti-tumor activity in preclinical in vitro and in vivo models of various cancers.

Research Area

Cardiovascular Research, Signal Transduction

Key Properties

• CAS Number: 1123837-84-2
• MW: 629.68
• Purity: 99.85% (May vary between batches)
• Formula: C₃₃H₂₉F₂N₅O₄S
• SMILES: COCCNCc1ccc(nc1)-c1cc2nccc(Oc3ccc(NC(=O)C4(CC4)C(=O)Nc4ccc(F)cc4)cc3F)c2s1
• Target: Trk receptor,FLT,Discoidin Domain Receptor (DDR),Ephrin Receptor,VEGFR,c-Kit,TAM Receptor
• Solubility: DMSO:50 mg/mL (79.41 mM);10% DMSO+90% Corn Oil:2.5 mg/mL (3.97 mM)

Bioactivity

• Target IC50:
  VEGFR3/FLT4:2 nM|Axl:1.5 nM|VEGFR2:5 nM|Mer:2 nM|VEGFR1:6 nM|DDR1:29 nM|FLT3:8 nM|EphA3:1 nM|DDR2:0.5 nM|TrkA:5 nM|TrkB:9 nM|c-Kit:6 nM
• In Vivo:
  Sitravatinib (MGCD516) has antitumor activity in nonClinicalal cancer models harboring genetic alterations of sitravatinib targets, including the rearrangement of NTRK, RET, or CHR4q12 amplification. In vivo tumor xenografts, MGCD516 causes the significant suppression of tumor growth. Efficacy of MGCD516 is superior to imatinib and crizotinib, two other well-studied multi-kinase inhibitors with overlapping target specificities, both in vitro and in vivo.
• In Vitro:
  Sitravatinib (MGCD516) is an inhibitor of a closely related spectrum of RTKs including RET, the split RTKs (PDGFR, VEGFR, and KIT), DDR2, TRK family, MET, and AXL. Sitravatinib causes the marked blockade of phosphorylation of potential driver RTKs and induced potent anti-proliferative effects in vitro.
• Cell Research:
  Cell lines: DDLS,LS141,and MPNST. Concentrations: 62.5,125,250,500,1000,2000 nM2,000-3,000 cells were plated in 96-well plates in RPMI/DME media with 10% FBS and then treated with the indicated drugs the next day.After 72 hours,media was replaced with 100 μL of media with 10% serum and 10% CCK-8 solution.After 1 hour,the optical density was read at 450 nm to determine viability.Background values from negative control wells without cells were subtracted for final sample quantification.Data was plotted as % cell viability compared to DMSO control.
• Animal Research:
  Animal Models: ICR/SCID mice. Formulation: 0.5% hydroxypropyl methylcellulose (HPMC) and 0.1% Tween-80 solution (pH 1.4). Dosages: 15 mg/kg. Administration: p.o.

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

c-Kit, cKit, Cluster of differentiation antigen 135, CD135, CD117, Discoidin Domain Receptor (DDR), Discoidin Domain Receptor, DiscoidinDomainReceptor, DiscoidinDomainReceptor(DDR), Axl, Cancer, kinase, KIT, immunotherapy, immune, inhibit, Macrophages, PD-1, MG 516, MG516, MG-516, MGCD 516, MGCD516, MGCD-516, Inhibitor, Mer, MER, FLT3, Ephrin Receptor, EphA3, EphrinReceptor, DDR2, DDR1, DDR, Fms like tyrosine kinase 3, Sitravatinib, TAMReceptor, TAM Receptor, SCFR, RTK, Tropomyosin related kinase receptor, Trk receptor, Trk Receptor, TRKA, TRKB, Trkreceptor, Tyrosine, VEGFR, VEGFR2, VEGFR1, Vascular endothelial growth factor receptor, VEGFR3, VEGFR3/FLT4

Compound Identifiers

PubChem CID

25212148