1232410-49-9 Usage
Description
3-Amino-6-[4-(methylsulfonyl)phenyl]-N-phenyl-2-pyrazinecarboxamide, also known as VE-821, is a potent and selective inhibitor of the DNA damage response kinase, ATR. It is a bright yellow solid that functions to disrupt the DNA damage repair system of tumor cells, thereby limiting their abilities for further growth and enhancing their susceptibility to cell death in response to radiation and chemotherapy.
Uses
Used in Oncology:
VE-821 is used as an inhibitor of ATMand Rad3-related (ATR) protein in human cancer cells. It is particularly effective in augmenting DNA damage and promoting cell death of cancer cells under both normal and hypoxic conditions, making it a valuable tool in the treatment of various types of cancer.
Used in Radiotherapy:
VE-821 is used to sensitize cancer cells to radiation therapy, enhancing the effectiveness of radiation in inducing cell death and inhibiting tumor growth.
Used in Chemotherapy:
VE-821 is also used to sensitize cancer cells to chemotherapy, increasing the efficacy of chemotherapeutic drugs and overcoming resistance in cancer treatment.
Used in Drug Development:
As an ATP-competitive inhibitor of ATR with an IC50 of 26 nM, VE-821 serves as a promising lead compound in the development of new drugs targeting the DNA damage response pathway in cancer therapy.
Biochem/physiol Actions
VE-821 is a potent ATP-competitive inhibitor of the DNA damage response (DDR) kinase Ataxia telangiectasia-mutated (ATM) and ATM- and Rad3-related (ATR) with a Ki of 13 nM. VE-821 has minimal cross-reactivity against the related PIKKs ATM, DNA-dependent protein kinase (DNA-PK), mTOR and PI3-kinase-γ (Ki of 16 μM, 2.2 μM, >1 μM and 3.9 μM, respectively) and against a large panel of unrelated protein kinases. VE-821 used alone caused death in a large fraction of cancer cell populations and also showed strong synergy with genotoxic agents. VE-821 increased sensitivity of cells to radiation and also sensitized cancer cells to a variety of chemotherapeutic agents.
References
Reaper et al. (2011), Selective killing of ATM- or p53-deficient cancer cells through inhibition of ATR; Nat. Chem. Biol., 7 428
Prevo et al. (2012), The novel ATR inhibitor VE-821 increases sensitivity of pancreatic cancer cells to radiation and chemotherapy; Cancer Biol. Ther., 13 1072
Huntoon et al. (2013), ATR inhibition broadly sensitizes ovarian cancer cells to chemotherapy independent of BRCA status; Cancer Res., 73 3683
King et al. (2021), Increased Replication Stress Determines ATR Inhibitor Sensitivity in Neuroblastoma Cells; Cancers (Basel), 13 6215
Moolmuang and Ruchirawat (2021), The antiproliferative effects of ataxia-telangiectasia mutated and ATM- and Rad3-related inhibitions and their enhancements with the cytotoxicity of DNA damaging agents in cholangiocarcinoma cells; J. Pharm. Pharmacol., 73 40
Check Digit Verification of cas no
The CAS Registry Mumber 1232410-49-9 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,2,3,2,4,1 and 0 respectively; the second part has 2 digits, 4 and 9 respectively.
Calculate Digit Verification of CAS Registry Number 1232410-49:
(9*1)+(8*2)+(7*3)+(6*2)+(5*4)+(4*1)+(3*0)+(2*4)+(1*9)=99
99 % 10 = 9
So 1232410-49-9 is a valid CAS Registry Number.
1232410-49-9Relevant articles and documents
COMPOUNDS USEFUL AS INHIBITORS OF ATR KINASE
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, (2011/12/02)
The present invention relates to pyrazine and pyridine compounds useful as inhibitors of ATR protein kinase. The invention also relates to pharmaceutically acceptable compositions comprising the compounds of this invention; methods of treating various diseases, disorders, and conditions using the compounds of this invention; processes for preparing the compounds of this invention; intermediates for the preparation of the compounds of this invention; and methods of using the compounds in in vitro applications, such as the study of kinases in biological and pathological phenomena; the study of intracellular signal transduction pathways mediated by such kinases; and the comparative evaluation of new kinase inhibitors. The compounds of this invention have formula (IV): (Formula (IV)) wherein the variables are as defined herein.
PYRAZINE DERIVATIVES USEFUL AS INHIBITORS OF ATR KINASE
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Page/Page column 176, (2010/08/05)
The present invention relates to pyrazine compounds useful as inhibitors of ATR protein kinase. The invention also relates to pharmaceutically acceptable compositions comprising the compounds of this invention; methods of treating of various diseases, disorders, and conditions using the compounds of this invention; processes for preparing the compounds of this invention; intermediates for the preparation of the compounds of this invention; and methods of using the compounds in in vitro applications, such as the study of kinases in biological and pathological phenomena; the study of intracellular signal transduction pathways mediated by such kinases; and the comparative evaluation of new kinase inhibitors. The compounds of this invention have formula (I):wherein the variables are as defined herein.
