1123837-84-2

Basic information

• Product Name: Sitravatinib
• Synonyms: Sitravatinib;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;MGCD-516;MG516;Sitravatinib (MGCD516)
• CAS NO: 1123837-84-2
• Molecular Formula: C₃₃H₂₉F₂N₅O₄S
• Molecular Weight: 629.6762664
• Mol File: 1123837-84-2.mol

Chemical Properties

• Boiling Point: 833.5±65.0 °C(Predicted)
• Appearance: /
• Density: 1.417±0.06 g/cm3(Predicted)
• Storage Temp.: -20°C
• Solubility: Soluble in DMSO (up to at least 25 mg/ml), or in Ethanol (up to at least 25 mg/ml)
• PKA: 13.17±0.70(Predicted)
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20°C for up to 1 month.
• CAS DataBase Reference: Sitravatinib(CAS DataBase Reference)
• NIST Chemistry Reference: Sitravatinib(1123837-84-2)
• EPA Substance Registry System: Sitravatinib(1123837-84-2)

Safety Data

• Hazardous Substances Data: 1123837-84-2(Hazardous Substances Data)

Usage

Uses

Used in Oncology:
Sitravatinib is used as an anticancer agent for the treatment of advanced cancers. It inhibits the activity of multiple receptor tyrosine kinases, which are often dysregulated in cancer cells, leading to reduced cell proliferation and tumor growth inhibition.
Used in Drug Development:
Sitravatinib serves as an intermediate in the preparation of substituted thienopyridines, which are inhibitors of protein tyrosine kinase activity. This makes it a valuable compound in the development of new therapeutic agents targeting kinase-mediated signaling pathways in various diseases, including cancer.
Used in Preclinical Research:
In preclinical studies, Sitravatinib has been shown to reduce the proliferation of various cancer cell lines, such as A-673, LPS141, MPNST, DDLS, and Saos-2, and decrease the phosphorylation of key signaling proteins like IGF1-R, PDGFRβ, and Akt. This makes it a useful tool for investigating the role of these kinases in cancer progression and for testing potential combination therapies in preclinical models.

References

1) Parag?et al.?(2016)?Significant blockade of multiple receptor kinases by MGCD516 (Sitravatinib), a novel small molecule inhibitor, shows potent anti-tumor activity in preclinical models of sarcoma; Oncotarget?7?4093 2) Leal?et al.?(2017)?Evidence of clinical activity of sitravatinib in combination with nivolumab in NSCLC patients progressing on prior checkpoint inhibitors; J. Thorac. Oncol.?12?S1803 3) Du?et al.?(2018);?Sitravatinib potentiates immune checkpoint blockade in refractory cancer models; JCI Insight?3?124184

Upstream product

• 1123837-28-4 tert-butyl [(6-bromopyridin-3-yl)methyl](2-methoxyethyl)carbamate 
• 149806-06-4 6-bromonicotinaldehyde 
• 1123837-99-9 N-((6-bromopyridin-3-yl)methyl)-2-methoxyethan-1-amine 
• 1123837-34-2 tert-butyl {[6-[7-(4-amino-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl]pyridin-3-yl]methyl}(2-methoxyethyl)carbamate 
• 1123838-02-7 tert-butyl {[6-(7-chlorothieno[3,2-b]pyridin-2-yl)pyridin-3-yl]methyl}(2-methoxyethyl)carbamate 
• 40258-99-9 1-(chlorocarbonyl)cyclopropane-1-carboxylic acid 
• 598-10-7 cyclopropane-1,1-dicarboxylic acid 
• 1341216-35-0 3-fluoro-4-hydroxybenzenaminium chloride 
• 1123837-39-7 tert-butyl ((6-(7-(2-fluoro-4-(1-((4-fluorophenyl)carbamoyl)cyclopropane-1-carboxamido)phenoxy)thieno[3,2-b]pyridin-2-yl)pyridin-3-yl)methyl)(2-methoxyethyl)carbamate 

Relevant articles and documents

TREATMENT OF CANCER WITH ANTI-OX40 ANTIBODIES AND MULTI-KINASE INHIBITORS

The present disclosure provides methods of treating cancer with non-competitive, agonist anti-OX40 antibodies and antigen-binding fragments thereof that bind to human OX40 (ACT35, CD134, or TNFRSF4), in combination with a multi-kinase inhibitor.

CRYSTALLINE FORM OF A MULTI-TYROSINE KINASE INHIBITOR, METHOD OF PREPARATION, AND USE THEREOF

The present invention relates to crystalline forms of 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 -di carboxamide (Compound 1), pharmaceutical compositions comprising the crystalline form, processes for preparing the crystalline form and methods of use therefore.

INHIBITORS OF PROTEIN TYROSINE KINASE ACTIVITY

The invention relates to compounds of Formula (I) and their use for inhibiting protein tyrosine kinase activity In Formula (I), the group M is thieno[3,2,b]pyridinyl as shown, and the group D is a ring or ring system, and the groups Z, Ar, and G are as defined herein The invention relates particularly to compounds that inhibit the protein tyrosine kinase activity of growth factor receptors, resulting in the inhibition of receptor signalling, for example, the inhibition of VEGF receptor signalling and HGF receptor signalling The invention also provides compositions and methods for treating cell proliferative diseases and conditions, such as cancer, and for treating ophthalmic diseases, including age-related macular degeneration (AMD) and diabetic retinopathy (DR)

PROCESSES AND INTERMEDIATES FOR PREPARING FUSED HETEROCYCLIC KINASE INHIBITORS

The invention relates to processes and intermediates for manufacturing fused heterocyclic-type kinase inhibitor compounds, such as thienopyridine-based compounds, and to processes and intermediates for preparing intermediates that are useful in the manufacture of fused heterocyclic-type kinase inhibitor compounds, particularly at an industrial level The processes are aimed at ultimately forming compounds of the formula (A) where M is thieno[3,2,b]pyridinyl as shown, the group D is a ring or ring system, preferably pyridine, and the group Z, Ar, and G are as defined herein Such compounds can act to inhibit the protein tyrosine kinase activity of growth factor receptors, resulting in the inhibition of receptor signalling, for example, the inhibition of VEGF receptor signalling and HGF receptor signalling.