ATM/ATR Inhibitor

Ceralasertib (AZD6738) is an orally active and bioavailable inhibitor of ATR kinase with an IC₅₀ of 1 nM.

AZD-7648 is a potent, orally active, selective DNA-PK inhibitor with an IC₅₀ of 0.6 nM. AZD-7648 induces apoptosis and shows antitumor activity.

KU-55933 is a potent ATM inhibitor with an IC₅₀ and K_i of 12.9 and 2.2 nM, respectively, and is highly selective for ATM as compared to DNA-PK, PI3K/PI4K, ATR and mTOR.

Berzosertib (VE-822) is an orally active, CNS-penetrant, and selective ATR kinase inhibitor. Berzosertib blocks ATR kinase activity, abrogates G₂/M cell cycle checkpoint, impairs DNA damage repair. Berzosertib induces apoptosis, inhibnits conlony migration, inhibits cell proliferation, and activates cGAS-STING axes in cancer cells. Berzosertib can be used for the research of cancers, such as head and neck squamous cell carcinoma, and colorectal cancer.

VE-821 is a potent ATP-competitive inhibitor of ATR with K_i/IC₅₀ of 13 nM/26 nM.

Elrelesertib (AZD1390) is an orally active, brain-penetrant ATM kinase inhibitor with IC₅₀ values of 0.78 nM. Elrelesertib blocks ATM-dependent DNA damage response, inhibits ATM autophosphorylation and downstream Chk2, Rad50 phosphorylation, and accumulates at DNA breaks. Elrelesertib acts as a radiosensitizer, induces apoptosis, genomic instability, G2-M cell cycle arrest, ROS elevation, and mitochondrial membrane potential alteration. Elrelesertib has low efflux liability against P-gp and BCRP. Elrelesertib can be used for the research of central nervous system malignancies, glioblastoma multiforme, glioma, lung cancer brain metastases, and breast cancer.

Abd110 is a selective ATR PROTAC degrader. Abd110 recruits Cereblon to induce the proteasomal degradation of ATR, and reduces the levels of phosphorylated ATR and downstream phosphorylated CHK1. Abd110 can be used for research on pancreatic cancer and cervical cancer.

Elimusertib (BAY-1895344) is a potent, orally active and selective ATR inhibitor with an IC₅₀ of 7 nM. Elimusertib has anti-tumor activity. Elimusertib can be used for the research of solid tumors and lymphomas.

AZD0156 is a potent, selective and orally active ATM inhibitor with an IC₅₀ of 0.58 nM. AZD0156 inhibits the ATM-mediated signaling, prevents DNA damage checkpoint activation, disrupts DNA damage repair, and induces tumor cell apoptosis.

KU-60019 is an improved ATM kinase-specific inhibitor with IC₅₀ of 6.3 nM.

Camonsertib (RP-3500) is an orally active, selective ATR kinase inhibitor (ATRi) with an IC₅₀ of 1.00 nM in biochemical assays. Camonsertib shows 30-fold selectivity for ATR over mTOR (IC₅₀=120 nM) and >2,000-fold selectivity over ATM, DNA-PK, and PI3Kα kinases. Camonsertib has potent antitumor activity.

Gartisertib (VX-803) is an ATP-competitive, orally active, and selective ATR inhibitor, with a K_i of <150 pM. Gartisertib potently inhibits ATR-driven phosphorylated checkpoint kinase-1 (Chk1) phosphorylation with an IC₅₀ of 8 nM. Antitumor activity.

Mirin is a potent Mre11-Rad50-Nbs1 (MRN) complex inhibitor. Mirin prevents MRN-dependent activation of ATM (IC₅₀=12 μM) without affecting ATM protein kinase activity, and it inhibits Mre11-associated exonuclease activity. Mirin abolishes the G2/M checkpoint and homology-dependent repair in mammalian cells. Mirin prevents ATM activation in response to DNA double-strand breaks (DSBs) and blocks homology-directed repair (HDR) in mammalian cells.

Tuvusertib (M1774; ATR inhibitor 1) is a selective and orally active ATR inhibitor extracted from patent WO2015187451A1, compound I-l, with a K_i value below 1 μΜ.

(E/Z)-Mirin is a mixture of (E)-Mirin and Mirin ((Z)-Mirin) (HY-19959) configurations. Among them, Mirin is an inhibitor of MRN (Mre11-Rad50-Nbs1). Mirin prevents MRN-dependent ATM activation without affecting ATM protein kinase activity.

ART0380 is a potent, selective and orally active ATR kinase inhibitor. ART0380 potently inhibits human ATR-ATRIP complex with an IC₅₀ of 51.7 nM. ART0380 binds the ATP pocket of the ATR-ATRIP complex, blocks ATR-dependent Chk1 serine 345 phosphorylation, and induces cell cycle disorder and DNA damage. ART0380 demonstrates potent and selective antitumor activity in preclinical models with varying types of ataxia-telangiectasia mutated (ATM) gene aberrancy. ART0380 can be used for the research of cancer, such as colorectal cancer and prostate cancer.

AZ20 is a potent and selective inhibitor of ATR with an IC₅₀ of 5 nM, and has 8-fold selectivity against mTOR (IC₅₀=38 nM).

Lartesertib (M4076) is an inhibitor of the serine/threonine protein kinase ATM with high potency. Lartesertib can inhibit the growth of multiple hematopoietic cell lines. Additionally, when combined with the ATR inhibitor Tuvusertib (HY-111451), Lartesertib can promote the death of tumor cells, activate the immune signaling pathway, and exhibit anti-tumor activity.

Elimusertib (BAY 1895344) hydrochloride is a potent, orally active and selective ATR inhibitor with an IC₅₀ of 7 nM. Elimusertib hydrochloride has anti-tumor activity. Elimusertib hydrochloride can be used for the research of solid tumors and lymphomas.

CGK733 is a potent ATM/ATR inhibitor, used for the research of cancer.