What is VE 821?

VE-821 is a potent and selective ATP competitive inhibitor of ATR with Ki/IC50 of 13 nM/26 nM in cell-free assays, shows inhibition of H2AX phosphorylation, minimal activity against PIKKs ATM, DNA-PK, mTOR and PI3Kγ. CAS No. 1232410-49-9. Size.

What are ATR inhibitors?

It is an ATR inhibitor, a promising class of new drugs that target the ATR (ataxia telangiectasia mutated and Rad3-related) kinase, which is involved in DNA damage repair. The drug inhibits the growth of tumor cells by limiting their ability to repair damaged DNA.

How is ATR inhibited?

Blocking ATR activity with small molecular inhibitors either alone or combined with DNA-damaging agents can lead to mitotic catastrophe of cancer cells and p53-independent cell death [13, 27]. ATR and/or CHK1 suppress replication stress that arises from causes such as DNA damage and oncogene activation.

What does ATR protein do?

ATR is a serine/threonine-specific protein kinase that is involved in sensing DNA damage and activating the DNA damage checkpoint, leading to cell cycle arrest in eukaryotes. ATR is activated in response to persistent single-stranded DNA, which is a common intermediate formed during DNA damage detection and repair.

How is ATR activated?

(A) ATR signaling is activated in response to single-stranded DNA gaps in the genome. Independent recruitment of several checkpoint proteins leads to TOPBP1-dependent activation of the kinase and phosphorylation of numerous substrates including CHK1 to regulate cellular responses to DNA damage and replication stress.

What is the ATR pathway?

Ataxia telangiectasia and Rad3-related (ATR) is an essential kinase that is active in S phase, senses stressed replication forks and orchestrates a multifaceted response to DNA replication stress. This response helps ensure completion of DNA replication and maintains the integrity of the genome.

What is ATR Signalling?

What are ATM and ATR?

What are ATM and ATR? Ataxia telangiectasia mutated (ATM) and ATM and RAD3-related (ATR) are members of the phosphatidyl- inositol 3-kinase (PI 3-kinase) like family of protein kinases (PIKKs).

What does the ATR gene do?

What are CHK1 and CHK2?

CHK1 and CHK2 are both activated upon DNA damage and can regulate cell division. CHK1 activity has been mostly implicated in the intra-S phase cell cycle checkpoint and the G2–M transition19. In contrast, CHK2 activity is associated with G1–S and G2–M arrests. CHK1 and CHK2 regulate different cell cycle proteins.

What is ATM CHK2?

ATM and Chk2 are activated potently by radiation and genotoxins that induce DSBs, but only weakly, if at all, by agents that block DNA replication without inducing damage (Matsuoka et al., 2000). In undamaged cells, ATM is thought to exist as inactive homodimers.

What is the p21 gene?

Cyclin-dependent kinase inhibitor 1, also known as CDK-interacting protein 1, or more simply as p21, is a cell cycle inhibitor that promotes both CDK/cyclin inhibition as well as cell cycle arrest during the G1/S phase. In humans, p21 is encoded by the CDKN1A gene on chromosome six.