Chk1 Inhibitor

BBI-355 (Compound 1) is an orally active, checkpoint kinase 1 (CHK1) inhibitor. BBI-355 is useful for the study of cancers with oncogene amplification.

Chk2-IN-1 (compound 1) is a potent and selective inhibitor of checkpoint kinase 2 (Chk2), with IC₅₀s of 13.5 nM and 220.4 nM for Chk2 and Chk1, respectively. Chk2-IN-1 can elicit a strong ataxia telangiectasia mutated (ATM)-dependent Chk2-mediated radioprotection effect.

GDC0575 (ARRY-575) hydrochloride is a highly-selective and orally active Chk1 (IC₅₀=1.2 nM) inhibitor. GDC0575 (ARRY-575) hydrochloride can be used for colitis-associated cancer (CAC) and colitis research.

CCT241533 dihydrochloride is a potent and selective ATP competitive inhibitor of CHK2 with an IC₅₀ of 3 nM and K_i of 1.16 nM.

CHK1-IN-9 (compound 11) is an orally active CHK1 inhibitor with an IC₅₀ value of 0.55 nM. CHK1-IN-9 can enhance the effect of DNA-damaging drugs on tumor cells. CHK1-IN-9 has synergistic anticancer effects with Gemcitabine (HY-17026).

CHK1-IN-13 (Compound 38) is a checkpoint kinase 1 (Chk1) inhibitor with an IC₅₀ of 10-50  nM. CHK1-IN-13 has anticancer activity, and can be used for the research of cancers, such as breast, ovarian and prostate cancer.

Multi-kinase-IN-6 (compound 10e) is a multikinase inhibitor that shows good enzyme inhibitory activity against TrkA, ALK2, c-KIT, EGFR, PIM1, CK2α, CHK1, and CDK2. Multi-kinase-IN-6 reveals antiproliferative activity against MCF7, HCT116 and EKVX with IC₅₀ values of 3.36 μM, 1.40 μM and 3.49 μM, respectively. Multi-kinase-IN-6 shows cell cycle arrest at the G1/S phase and G1 phase in MCF7 and HCT116 cells with good apoptotic effect.

CHK1-IN-14 is a free base form of CHK1 inhibitor. CHK1-IN-14 can be used in research on resistance to chemotherapy and radiotherapy.

DB07006 (compound 18) is a potent, ATP-cpmpetitive dual inhibitor of Wee1 (IC₅₀ = 0.030 μM) and Chk1 checkpoint kinases (IC₅₀ = 0.018 μM). DB07006 demonstrates effective abrogation of the G2/M checkpoint in combination with DNA-damaging agents in cellular models. DB07006 can be used for cancer research.

CHK1-IN-12 (Compound example 1-5) is an orally active and highly selective checkpoint kinase 1 (CHK1) inhibitor with in vitro enzyme IC₅₀≤10 nM and cellular IC₅₀≤50 nM. CHK1-IN-12 inhibits the phosphorylation activity of CHK1 kinase to block the DNA damage response pathway, inducing tumor cell cycle arrest and apoptosis. CHK1-IN-12 is promising for research of cancers.

CBP-93872 is a G2 checkpoint inhibitor and a chemosensitizer. CBP-93872 specifically inhibits DNA double-strand break (DSB)-dependent, Nbs1-mediated ATR activation, without directly inhibiting ATR kinase activity or affecting ATR activation induced by other types of DNA damage; meanwhile, it suppresses the pathway between ATM and ATR activation, thereby reducing the autophosphorylation of ATR and the subsequent phosphorylation of Chk1. CBP-93872 does not inhibit DNA end resection at DSB sites. CBP-93872 induces cell death and enhances the cytotoxic effects of platinum-containing compounds and pyrimidine antimetabolites on cancer cells. CBP-93872 can be used in related research on p53-mutant cancers, colorectal cancer, and pancreatic cancer.

PV1162 is a selective Chk2 inhibitor with an IC₅₀ of 0.29 nM. PV1162 inhibits ATP binding to Chk2 by targeting the gatekeeper-dependent hydrophobic pocket, which is specific to Chk2 and located behind the ATP-binding site (adenine-binding region), thereby inhibiting the phosphorylation activity of Chk2. PV1162 holds potential application value in the field of cancer therapy.

Prexasertib lactate (LY2606368 lactate) is the lactate form of Prexasertib (HY-18174). Prexasertib lactate is a selective, ATP-competitive second-generation checkpoint kinase 1 (CHK1) inhibitor with a K_i of 0.9 nM and an IC₅₀ of <1 nM. Prexasertib lactate inhibits CHK2 (IC₅₀=8 nM) and RSK1 (IC₅₀=9 nM). Prexasertib lactate causes double-stranded DNA breakage and replication catastrophe resulting in apoptosis. Prexasertib lactate shows potent anti-tumor activity.

CHK1-IN-4 is a selective checkpoint kinase 1 (Chk1) inhibitor with an IC₅₀ ≤ 1 nM. The IC₅₀ value of CHK1-IN-4 against Chk2 ranges from 50 to 100 nM. CHK1-IN-4 inhibits cancer cell proliferation and exhibits antitumor activity in colon cancer xenograft models. CHK1-IN-4 can be used for the research of colon cancer and breast cancer.

GDC-0425 hydrochloride (RG-7602 hydrochloride) is an orally active, highly selective ChK1 inhibitor. GDC-0425 hydrochloride abrogates cell cycle arrest and inhibits genomic repair. GDC-0425 hydrochloride potently suppresses Gemcitabine (HY-17026)-induced pCDK1/2 expression. GDC-0425 hydrochloride can be used in research related to osteosarcoma, ovarian cancer, basal (triple-negative) breast cancer, and colorectal cancer.

CHK-IN-1 is an inhibitor of CHK1 and CHK2, with anti-proliferative activities.