ATM Inhibitor

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.

AZD1390 is a potent, highly selective, orally bioavailable, brain-penetrant ATM inhibitor with an IC₅₀ of 0.78 nM in cell.

ATR-IN-31 is a selective ATR kinase inhibitor with an IC₅₀ of 7 nM. ATR-IN-31 does not significantly inhibit ATM kinase activity. ATR-IN-31 inhibits viability of prostate cancer cells.ATR-IN-31 can be used for the research of prostate cancer.

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

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.

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.

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

ETP-46464 is an effective mTOR and ATR inhibitor with IC₅₀s of 0.6 and 14 nM, respectively.

Ro 90-7501 is an amyloid β₄₂ (Aβ₄₂) fibril assembly inhibitor that reduces Aβ₄₂-induced cytotoxicity (EC₅₀ of 2 μM). Ro 90-7501 inhibits ATM phosphorylation and DNA repair. RO 90-7501 selectively enhances toll-like receptor 3 (TLR3) and RIG-I-like receptor (RLR) ligand-induced IFN-β gene expression and antiviral response. Ro 90-7501 also inhibits protein phosphatase 5 (PP5) in a TPR-dependent manner. Ro 90-7501 has significant radiosensitizing effects on cervical cancer cells.

CP-466722 is a rapidly reversible inhibitor of ATM, with an IC₅₀ of 0.41 μM, and has no effects on PI3K or closely related PI3K-like protein kinase (PIKK) family members.

AZ31 is a a potent, highly selective, and orally active ATM inhibitor with an IC₅₀ of <1.2 nM for ATM enzyme, and an IC₅₀ of 46 nM for ATM in cell. AZ31 shows excellent selectivity over ATR (>500-fold) and excellent PIKK-family selectivity and pan-kinase selectivity. AZ31 is a potent radiosensitizer in vitro, it can be used for the research of cancer.

AZ32 is an orally bioavailable and blood-brain barrier-penetrating ATM inhibitor with an IC₅₀ of <6.2 nM for ATM enzyme, and an IC₅₀ of 0.31 μM for ATM in cell.

ATM Inhibitor-1 is a highly potent, selective and orally active ATM inhibitor, with an IC₅₀ of 0.7 nM, shows weak activity against mTOR (IC₅₀, 21 μM), DNAPK (IC₅₀, 2.8 μM), PI3Kα (IC₅₀, 3.8 μM), PI3Kβ (IC₅₀, 10.3 μM), PI3Kγ (IC₅₀, 3 μM) and PI3Kδ (IC₅₀, 0.73 μM). ATM Inhibitor-1 exhibits anti-tumor activity.

ATM Inhibitor-3 (compound 34) is a potent and selective ATM inhibitor, with an IC₅₀ of 0.71 nM. ATM Inhibitor-3 shows inhibition of PI3K kinases family. ATM Inhibitor-3 exhibits favorable metabolic stability.

ATR/PARP1-IN-1 is a potent ATR and PARP1 dual inhibitor with IC₅₀s of 17.3 nM and 0.38 nM, respectively. ATR/PARP1-IN-1 effectively reduces cell viability, induces apoptosis and DNA damage. ATR/PARP1-IN-1 significantly impairs triple-negative breast cancer (TNBC) colony formation, migration, and invasion. ATR/PARP1-IN-1 suppresses tumor growth effectively in MDA-MB-468 xenografted mice, with no significant body weight change.