1276105-89-5

Basic information

• Product Name: CNX-1351
• Synonyms: CNX-1351;1-[4-[[2-(1H-Indazol-4-yl)-4-(4-morpholinyl)thieno[3,2-d]pyrimidin-6-yl]methyl]-1-piperazinyl]-6-methyl-5-heptene-1,4-dione;1-[4-[[2-(1H-Indazol-4-yl)-4-(4-morpholinyl)thieno[3,2-d]pyrimidin-6-yl]methyl]-1-piperazinyl]-6-methyl-5-heptene-1,4-dione CNX1351;CNX-1351, >=98%
• CAS NO: 1276105-89-5
• Molecular Formula: C30H35N7O3S
• Molecular Weight: 573.709
• Product Categories: Inhibitors
• Mol File: 1276105-89-5.mol
• Article Data: 2

Chemical Properties

• Appearance: /
• CAS DataBase Reference: CNX-1351(CAS DataBase Reference)
• NIST Chemistry Reference: CNX-1351(1276105-89-5)
• EPA Substance Registry System: CNX-1351(1276105-89-5)

Safety Data

• Hazardous Substances Data: 1276105-89-5(Hazardous Substances Data)

Usage

General Description

CNX-1351 is a novel small-molecule inhibitor of the MTH1 protein, which plays a key role in maintaining the nucleotide pool balance and protecting cancer cells from oxidative damage. By inhibiting MTH1, CNX-1351 disrupts the ability of cancer cells to repair oxidative DNA damage, leading to the accumulation of DNA damage and ultimately cell death. This mechanism of action makes CNX-1351 a promising candidate for the treatment of various cancers, particularly those with high levels of oxidative stress or DNA damage. Additionally, CNX-1351 has shown potential for use in combination therapies with other cancer treatments, further enhancing its therapeutic potential.

Upstream product

• 885618-31-5 2-chloro-4-morpholinothieno[3,2-d]pyrimidine-6-carbaldehyde 
• 885699-79-6 4-(2-chloro-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-6-ylmethyl)-piperazine-1-carboxylic acid tert-butyl ester 
• 54608-07-0 6-methyl-4-oxohept-5-enoic acid 

Relevant articles and documents

Discovery of a potent and isoform-selective targeted covalent inhibitor of the lipid kinase PI3Kα

PI3Kα has been identified as an oncogene in human tumors. By use of rational drug design, a targeted covalent inhibitor 3 (CNX-1351) was created that potently and specifically inhibits PI3Kα. We demonstrate, using mass spectrometry and X-ray crystallography, that the selective inhibitor covalently modifies PI3Kα on cysteine 862 (C862), an amino acid unique to the α isoform, and that PI3Kβ, -γ, and -δ are not covalently modified. 3 is able to potently (EC50 50 100 nM). A covalent probe, 8 (CNX-1220), which selectively bonds to PI3Kα, was used to investigate the duration of occupancy of 3 with PI3Kα in vivo. This is the first report of a PI3Kα-selective inhibitor, and these data demonstrate the biological impact of selectively targeting PI3Kα.