Sitravatinib free base | CAS#1123837-84-2 | RTK inhibitor

MedKoo Cat#: 206510 | Name: Sitravatinib free base

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Sitravatinib, also known as MGCD516 or MG516, is a novel small molecule inhibitor targeting multiple RTKs involved in driving sarcoma cell growth. MGCD516 treatment resulted in significant blockade of phosphorylation of potential driver RTKs and induced potent anti-proliferative effects in vitro. MGCD516 treatment of tumor xenografts in vivo resulted in significant suppression of tumor growth.

Chemical Structure

Sitravatinib free base

CAS#1123837-84-2 (free base)

Theoretical Analysis

MedKoo Cat#: 206510

Name: Sitravatinib free base

CAS#: 1123837-84-2 (free base)

Chemical Formula: C33H29F2N5O4S

Exact Mass: 629.1908

Molecular Weight: 629.68

Elemental Analysis: C, 62.95; H, 4.64; F, 6.03; N, 11.12; O, 10.16; S, 5.09

Price and Availability

Size	Price	Availability
10mg	USD 90.00	Ready to ship
25mg	USD 150.00	Ready to ship
50mg	USD 250.00	Ready to ship
100mg	USD 450.00	Ready to ship
200mg	USD 750.00	Ready to ship
500mg	USD 1,650.00	Ready to ship
1g	USD 2,950.00	2 weeks
2g	USD 5,250.00	2 Weeks

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Related CAS #

2244864-88-6 (malate) 1123837-84-2 (free base)

Synonym

MGCD516; MGCD-516; MGCD 516; MG516; MG 516; MG-516; Sitravatinib;

IUPAC/Chemical Name

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

InChi Key

IJJSWVSWWGOJGM-UHFFFAOYSA-N

InChi Code

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

SMILES Code

O=C(C1(C(NC2=CC=C(F)C=C2)=O)CC1)NC3=CC=C(OC4=C5C(C=C(C6=NC=C(CNCCOC)C=C6)S5)=NC=C4)C(F)=C3

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, DMF, and ethanol

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#C24R02B08

QC Data

View QC data: current batch, Lot#C24R02B08

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Sitravatinib inhibits 35 kinases (IC50s = 0.5-5,550 nM) in a panel of 55 RTKs. Sitravatinib reduces proliferation of A-673, LPS141, MPNST, DDLS, and Saos-2 cancer cells (IC50s = 1,750, 340.1, 705.7, 266, and 1,830 nM, respectively).

In vitro activity:

Sitravatinib has potential as an alternative treatment for acute myeloid leukemia (AML) patients resistant to current FLT3 inhibitors. Sitravatinib exhibited notable growth inhibitory effects, induced cell cycle arrest and apoptosis in FLT3-ITD AML cell lines. Sitravatinib displayed a potent inhibitory effect on FLT3-ITD-F691L mutation which conferred resistance to gilteritinib and all other FLT3 inhibitors available. Reference: Biomark Res. 2023 Jan 24;11(1):8. https://pubmed.ncbi.nlm.nih.gov/36691065/

In vivo activity:

MGCD516 is superior to imatinib and crizotinib and has potential for the treatment of patients with soft-tissue sarcoma. MGCD516 creates a blockade of multiple driver signaling pathways, providing a rationale for further clinical development. Reference: Oncotarget. 2016 Jan 26;7(4):4093-109. https://pubmed.ncbi.nlm.nih.gov/26675259/

	Solvent	mg/mL	mM
Solubility
	DMF	5.0	7.94
	DMSO	5.0	15.88
	Ethanol	10.0	7.94

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 629.68 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Zhang Y, Wang P, Wang Y, Shen Y. Sitravatinib as a potent FLT3 inhibitor can overcome gilteritinib resistance in acute myeloid leukemia. Biomark Res. 2023 Jan 24;11(1):8. doi: 10.1186/s40364-022-00447-4. PMID: 36691065; PMCID: PMC9872318. 2. Du W, Huang H, Sorrelle N, Brekken RA. Sitravatinib potentiates immune checkpoint blockade in refractory cancer models. JCI Insight. 2018 Nov 2;3(21):e124184. doi: 10.1172/jci.insight.124184. PMID: 30385724; PMCID: PMC6238734. 3. Msaouel P, Sweis RF, Bupathi M, Heath E, Goodman OB Jr, Hoimes CJ, Milowsky MI, Davis N, Kalebasty AR, Picus J, Shaffer D, Mao S, Adra N, Yorio J, Gandhi S, Grivas P, Siefker-Radtke A, Yang R, Latven L, Olson P, Chin CD, Der-Torossian H, Mortazavi A, Iyer G. A Phase 2 Study of Sitravatinib in Combination with Nivolumab in Patients with Advanced or Metastatic Urothelial Carcinoma. Eur Urol Oncol. 2023 Dec 16:S2588-9311(23)00282-1. doi: 10.1016/j.euo.2023.12.001. Epub ahead of print. PMID: 38105142. 4. Patwardhan PP, Ivy KS, Musi E, de Stanchina E, Schwartz GK. 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. doi: 10.18632/oncotarget.6547. PMID: 26675259; PMCID: PMC4826192.

In vitro protocol:

In vivo protocol:

1. Msaouel P, Sweis RF, Bupathi M, Heath E, Goodman OB Jr, Hoimes CJ, Milowsky MI, Davis N, Kalebasty AR, Picus J, Shaffer D, Mao S, Adra N, Yorio J, Gandhi S, Grivas P, Siefker-Radtke A, Yang R, Latven L, Olson P, Chin CD, Der-Torossian H, Mortazavi A, Iyer G. A Phase 2 Study of Sitravatinib in Combination with Nivolumab in Patients with Advanced or Metastatic Urothelial Carcinoma. Eur Urol Oncol. 2023 Dec 16:S2588-9311(23)00282-1. doi: 10.1016/j.euo.2023.12.001. Epub ahead of print. PMID: 38105142. 2. Patwardhan PP, Ivy KS, Musi E, de Stanchina E, Schwartz GK. 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. doi: 10.18632/oncotarget.6547. PMID: 26675259; PMCID: PMC4826192.

1: Ajadee A, Mahmud S, Hossain MB, Ahmmed R, Ali MA, Reza MS, Sarker SK, Mollah MNH. Screening of differential gene expression patterns through survival analysis for diagnosis, prognosis and therapies of clear cell renal cell carcinoma. PLoS One. 2024 Sep 30;19(9):e0310843. doi: 10.1371/journal.pone.0310843. PMID: 39348357; PMCID: PMC11441673. 2: Li J, Bai Y, Chen Z, Ying J, Guo Y, Fang W, Zhang F, Xiong J, Zhang T, Meng Z, Zhang J, Ren Z, Hao C, Chen Y, Lin X, Pan H, Zhou F, Li X, Yu F, Zhang J, Zhang Z, Qin S. SAFFRON-104: a phase Ib/II study of sitravatinib alone or with tislelizumab in advanced hepatocellular carcinoma and gastric cancer/gastroesophageal junction cancer. Cancer Immunol Immunother. 2024 Sep 5;73(11):219. doi: 10.1007/s00262-024-03806-2. PMID: 39235596; PMCID: PMC11377389. 3: Pant S, Cho BC, Kyriakopoulos CE, Spira A, Tannir N, Werner TL, Yan X, Neuteboom S, Chao R, Goel S. Targeting multiple receptor tyrosine kinases with sitravatinib: A Phase 1b study in advanced renal cell carcinoma and castrate- resistant prostate cancer. Invest New Drugs. 2024 Aug 21. doi: 10.1007/s10637-024-01465-9. Epub ahead of print. PMID: 39168901. 4: Demirsoy S, Tran H, Liu J, Li Y, Yang S, Aregawi D, Glantz MJ, Jacob NK, Walter V, Schell TD, Olmez I. Targeting Tyro3, Axl, and MerTK Receptor Tyrosine Kinases Significantly Sensitizes Triple-Negative Breast Cancer to CDK4/6 Inhibition. Cancers (Basel). 2024 Jun 18;16(12):2253. doi: 10.3390/cancers16122253. PMID: 38927958; PMCID: PMC11202171. 5: Dickinson A, Liu Y, Uvarov A, Peyret T, Marier JF, Chin C, Tran JQ. Concentration-QTc modeling of sitravatinib in patients with advanced solid malignancies. Clin Transl Sci. 2024 May;17(5):e13808. doi: 10.1111/cts.13808. PMID: 38700272; PMCID: PMC11067505. 6: Rozen EJ, Frantz W, Wigglesworth K, Vessella T, Zhou HS, Shohet JM. Blockade of Discoidin Domain Receptor Signaling with Sitravatinib Reveals DDR2 as a Mediator of Neuroblastoma Pathogenesis and Metastasis. Mol Cancer Ther. 2024 Aug 1;23(8):1124-1138. doi: 10.1158/1535-7163.MCT-23-0741. PMID: 38670553. 7: Wang S, Zhu L, Li T, Lin X, Zheng Y, Xu D, Guo Y, Zhang Z, Fu Y, Wang H, Wang X, Zou T, Shen X, Zhang L, Lai N, Lu L, Qin L, Dong Q. Disruption of MerTK increases the efficacy of checkpoint inhibitor by enhancing ferroptosis and immune response in hepatocellular carcinoma. Cell Rep Med. 2024 Feb 20;5(2):101415. doi: 10.1016/j.xcrm.2024.101415. PMID: 38382467; PMCID: PMC10897610. 8: Wang X, Pan H, Cui J, Chen X, Yoon WH, Carlino MS, Li X, Li H, Zhang J, Sun J, Guo J, Cui C. SAFFRON-103: a phase Ib study of sitravatinib plus tislelizumab in anti-PD-(L)1 refractory/resistant advanced melanoma. Immunotherapy. 2024 Mar;16(4):243-256. doi: 10.2217/imt-2023-0130. Epub 2024 Jan 10. PMID: 38197138. 9: Msaouel P, Sweis RF, Bupathi M, Heath E, Goodman OB Jr, Hoimes CJ, Milowsky MI, Davis N, Kalebasty AR, Picus J, Shaffer D, Mao S, Adra N, Yorio J, Gandhi S, Grivas P, Siefker-Radtke A, Yang R, Latven L, Olson P, Chin CD, Der-Torossian H, Mortazavi A, Iyer G. A Phase 2 Study of Sitravatinib in Combination with Nivolumab in Patients with Advanced or Metastatic Urothelial Carcinoma. Eur Urol Oncol. 2024 Aug;7(4):933-943. doi: 10.1016/j.euo.2023.12.001. Epub 2023 Dec 16. PMID: 38105142. 10: Sweeney R, Omstead AN, Fitzpatrick JT, Zheng P, Gorbunova A, Grayhack EE, Goel A, Khan AF, Kosovec JE, Wagner PL, Jobe BA, Kelly RJ, Zaidi AH. Sitravatinib combined with PD-1 blockade enhances cytotoxic T-cell infiltration by M2 to M1 tumor macrophage repolarization in esophageal adenocarcinoma. Carcinogenesis. 2024 Apr 12;45(4):210-219. doi: 10.1093/carcin/bgad087. PMID: 38019590. 11: Borghaei H, de Marinis F, Dumoulin D, Reynolds C, Theelen WSME, Percent I, Gutierrez Calderon V, Johnson ML, Madroszyk-Flandin A, Garon EB, He K, Planchard D, Reck M, Popat S, Herbst RS, Leal TA, Shazer RL, Yan X, Harrigan R, Peters S; SAPPHIRE Investigators. SAPPHIRE: phase III study of sitravatinib plus nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. Ann Oncol. 2024 Jan;35(1):66-76. doi: 10.1016/j.annonc.2023.10.004. Epub 2023 Oct 20. PMID: 37866811. 12: Mirmajidi SH, Irajie C, Savardashtaki A, Negahdaripour M, Nezafat N, Ghasemi Y. Identification of potential RapJ hits as sporulation pathway inducer candidates in Bacillus coagulans via structure-based virtual screening and molecular dynamics simulation studies. J Mol Model. 2023 Jul 18;29(8):256. doi: 10.1007/s00894-023-05664-8. Erratum in: J Mol Model. 2023 Sep 16;29(10):317. doi: 10.1007/s00894-023-05726-x. PMID: 37464224. 13: Minchom A, Popat S. Sitravatinib and Acquired Immune Checkpoint Inhibitor Resistance: A Gem for the Future? J Thorac Oncol. 2023 Jul;18(7):830-833. doi: 10.1016/j.jtho.2023.03.023. PMID: 37348988. 14: Lu H, Zhang B, Xie Y, Zhao W, Han W, Zhou L, Wang Z. Sitravatinib is a potential EGFR inhibitor and induce a new death phenotype in Glioblastoma. Invest New Drugs. 2023 Aug;41(4):564-578. doi: 10.1007/s10637-023-01373-4. Epub 2023 Jun 16. PMID: 37322389. 15: Karam JA, Msaouel P, Haymaker CL, Matin SF, Campbell MT, Zurita AJ, Shah AY, Wistuba II, Marmonti E, Duose DY, Parra ER, Soto LMS, Laberiano-Fernandez C, Lozano M, Abraham A, Hallin M, Chin CD, Olson P, Der-Torossian H, Yan X, Tannir NM, Wood CG. Phase II trial of neoadjuvant sitravatinib plus nivolumab in patients undergoing nephrectomy for locally advanced clear cell renal cell carcinoma. Nat Commun. 2023 May 10;14(1):2684. doi: 10.1038/s41467-023-38342-7. PMID: 37164948; PMCID: PMC10172300. 16: Reck M, Popat S, Grohé C, Corral J, Novello S, Gottfried M, Brueckl W, Radonjic D, Kaiser R, Heymach J. Anti-angiogenic agents for NSCLC following first-line immunotherapy: Rationale, recent updates, and future perspectives. Lung Cancer. 2023 May;179:107173. doi: 10.1016/j.lungcan.2023.03.009. Epub 2023 Mar 15. PMID: 36940614. 17: He K, Berz D, Gadgeel SM, Iams WT, Bruno DS, Blakely CM, Spira AI, Patel MR, Waterhouse DM, Richards DA, Pham A, Jotte R, Hong DS, Garon EB, Traynor A, Olson P, Latven L, Yan X, Shazer R, Leal TA. MRTX-500 Phase 2 Trial: Sitravatinib With Nivolumab in Patients With Nonsquamous NSCLC Progressing On or After Checkpoint Inhibitor Therapy or Chemotherapy. J Thorac Oncol. 2023 Jul;18(7):907-921. doi: 10.1016/j.jtho.2023.02.016. Epub 2023 Feb 24. PMID: 36842467; PMCID: PMC10330304. 18: Zhao J, Yu X, Huang D, Ma Z, Gao B, Cui J, Chu Q, Zhou Q, Sun M, Day D, Wu J, Pan H, Wang L, Voskoboynik M, Wang Z, Liu Y, Li H, Zhang J, Peng Y, Wu YL. SAFFRON-103: a phase 1b study of the safety and efficacy of sitravatinib combined with tislelizumab in patients with locally advanced or metastatic non- small cell lung cancer. J Immunother Cancer. 2023 Feb;11(2):e006055. doi: 10.1136/jitc-2022-006055. PMID: 36808075; PMCID: PMC9944269. 19: Zhang Y, Wang P, Wang Y, Shen Y. Sitravatinib as a potent FLT3 inhibitor can overcome gilteritinib resistance in acute myeloid leukemia. Biomark Res. 2023 Jan 24;11(1):8. doi: 10.1186/s40364-022-00447-4. PMID: 36691065; PMCID: PMC9872318. 20: Ingham M, Lee S, Van Tine BA, Choy E, Oza J, Doshi S, Ge L, Oppelt P, Cote G, Corgiat B, Sender N, Sta Ana S, Panchalingam L, Petricoin E, Schwartz GK. A Single-Arm Phase II Trial of Sitravatinib in Advanced Well- Differentiated/Dedifferentiated Liposarcoma. Clin Cancer Res. 2023 Mar 14;29(6):1031-1039. doi: 10.1158/1078-0432.CCR-22-3351. PMID: 36548343.