Sitravatinib

Chemical compound

L01EX26 (WHO)

Identifiers

IUPAC name

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

CAS Number

1123837-84-2

ChemSpider

52083477

UNII

CWG62Q1VTB

KEGG

D11140

CompTox Dashboard (EPA)

DTXSID801100124

Chemical and physical dataFormulaC₃₃H₂₉F₂N₅O₄SMolar mass629.68 g·mol⁻¹3D model (JSmol)

Interactive image

SMILES

COCCNCc1ccc(nc1)c2cc3c(s2)c(ccn3)Oc4ccc(cc4F)NC(=O)C5(CC5)C(=O)Nc6ccc(cc6)F

InChI

InChI=1S/C33H29F2N5O4S/c1-43-15-14-36-18-20-2-8-25(38-19-20)29-17-26-30(45-29)28(10-13-37-26)44-27-9-7-23(16-24(27)35)40-32(42)33(11-12-33)31(41)39-22-5-3-21(34)4-6-22/h2-10,13,16-17,19,36H,11-12,14-15,18H2,1H3,(H,39,41)(H,40,42)
Key:WLAVZAAODLTUSW-UHFFFAOYSA-N

Sitravatinib (MGCD516) is an experimental drug for the treatment of cancer. It is a small molecule inhibitor of multiple tyrosine kinases.^[1]

Sitravatinib is being developed by Mirati Therapeutics.^[2]

Ongoing phase II trials include a trial for liposarcoma,^[3] a combination trial for non-small cell lung cancer,^[4] and a combination trial with nivolumab for renal cell carcinoma.^[5] Sitravatinib is being evaluated in ongoing trials in patients with advanced non-small cell lung cancer, including in a combination trial with nivolumab in those who are resistant to checkpoint inhibitor therapy, and certain patients who are naïve to checkpoint inhibitor therapy.^[6]

References

^ Yang Y, Ji N, Cai CY, Wang JQ, Lei ZN, Teng QX, Wu ZX, Cui Q, Pan Y, Chen ZS (July 2020). "Modulating the function of ABCB1: in vitro and in vivo characterization of sitravatinib, a tyrosine kinase inhibitor". Cancer Communications. 40 (7): 285–300. doi:10.1002/cac2.12040. PMC 7365458. PMID 32525624.
^ "Sitravatinib | Mirati Therapeutics, Inc".
^ Clinical trial number NCT02978859 for "MGCD516 in Advanced Liposarcoma and Other Soft Tissue Sarcomas" at ClinicalTrials.gov
^ Clinical trial number NCT02954991 for "Phase 2 Study of Glesatinib, Sitravatinib or Mocetinostat in Combination With Nivolumab in Non-Small Cell Lung Cancer" at ClinicalTrials.gov
^ Clinical trial number NCT03015740 for "MGCD516 Combined With Nivolumab in Renal Cell Cancer (RCC)" at ClinicalTrials.gov
^ "A Randomized Phase 3 Study of Sitravatinib in Combination with Nivolumab Versus Docetaxel in Patients with Advanced Non-Squamous Non-Small Cell Lung Cancer with Disease Progression on or After Platinum-Based Chemotherapy and Checkpoint Inhibitor Therapy SAPPHIRE". 28 February 2022.

Targeted cancer therapy / antineoplastic agents (L01)

CI monoclonal antibodies ("-mab")

Receptor tyrosine kinase	ErbB: HER1/EGFR (Cetuximab Panitumumab) HER2/neu (Pertuzumab, Trastuzumab (+hyaluronidase) Trastuzumab emtansine Trastuzumab deruxtecan)
Others for solid tumors	EpCAM (Catumaxomab Edrecolomab) VEGF-A (Bevacizumab)
Leukemia/lymphoma	lymphoid: CD3 (Glofitamab, Elranatamab, Mosunetuzumab), CD20 (Glofitamab Ibritumomab Mosunetuzumab Obinutuzumab Ofatumumab Rituximab Tositumomab), CD30 (Brentuximab), CD52 (Alemtuzumab) myeloid: CD33 (Gemtuzumab ozogamicin)
Other	Amivantamab Atezolizumab Avelumab Axatilimab Belantamab mafodotin Bermekimab Blinatumomab Cemiplimab Daratumumab Dinutuximab beta Dostarlimab Durvalumab Elotuzumab Enfortumab vedotin Epcoritamab Inotuzumab ozogamicin Ipilimumab Isatuximab Loncastuximab tesirine Mirvetuximab soravtansine Mogamulizumab Moxetumomab pasudotox Naxitamab Necitumumab Nivolumab Olaratumab Oportuzumab monatox Pembrolizumab Polatuzumab vedotin Prolgolimab Ramucirumab Retifanlimab Sabatolimab Sacituzumab govitecan Serplulimab Sugemalimab Tafasitamab Talquetamab Tarlatamab Teclistamab Tislelizumab Tisotumab vedotin Toripalimab Tremelimumab

Tyrosine kinase inhibitors ("-nib")

Receptor tyrosine kinase	ErbB: HER1/EGFR (Afatinib Aumolertinib Brigatinib Dacomitinib Erlotinib Gefitinib Icotinib Lazertinib Mobocertinib Olmutinib Osimertinib Rociletinib Vandetanib) HER1/EGFR and HER2/neu Lapatinib Neratinib Tucatinib RTK class III: C-kit and PDGFR (Avapritinib Axitinib Masitinib Pazopanib Ripretinib Sorafenib Sunitinib Toceranib) FLT3 (Lestaurtinib, Gilteritinib (AXL, ALK, LTK)) VEGFR Axitinib Cediranib Fruquintinib Lenvatinib Nintedanib Pazopanib Regorafenib Semaxanib Sorafenib Sunitinib Tivozanib Toceranib Vandetanib ALK Alectinib Brigatinib Ceritinib RET inhibitors: Entrectinib (ALK, ROS1, NTRK), Futibatinib (FGFR2), Infigratinib, Larotrectinib (NTRK), Pemigatinib (FGFR), Pralsetinib, Repotrectinib (ROS1, TRK, ALK), Selpercatinib (VEGFR, FGFR), Vandetanib (VEGFR, EGFR). c-MET inhibitors: Cabozantinib (VEGFR), Capmatinib, Crizotinib (ALK)
Non-receptor	bcr-abl Asciminib Bosutinib Dasatinib Imatinib Nilotinib Ponatinib Radotinib Src (Bosutinib Dasatinib) Janus kinase Baricitinib Fedratinib Filgotinib Lestaurtinib Momelotinib Pacritinib Ruxolitinib MAP2K Binimetinib Cobimetinib Selumetinib Trametinib EML4-ALK Crizotinib Entrectinib Lorlatinib Bruton's Acalabrutinib Ibrutinib Orelabrutinib Pirtobrutinib Zanubrutinib

Receptor tyrosine kinase