Chk1 Inhibitor

Prexasertib (LY2606368) 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 inhibits CHK2 (IC₅₀=8 nM) and RSK1 (IC₅₀=9 nM). Prexasertib causes double-stranded DNA breakage and replication catastrophe resulting in apoptosis. Prexasertib shows potent anti-tumor activity.

AZD-7762 is a potent ATP-competitive checkpoint kinase (Chk) inhibitor in with an IC₅₀ of 5 nM for Chk1.

Rabusertib (LY2603618) is a potent and selective inhibitor of Chk1 with an IC₅₀ of 7 nM.

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.

CCT245737 (SRA737) is an orally active and seletive Chk1 inhibitor, with an IC₅₀ of 1.3 nM.

SCH900776 (MK-8776) is a potent, selective and orally bioavailable inhibitor of checkpoint kinase1 (Chk1) with an IC₅₀ of 3 nM. SCH900776 shows 50- and 500-fold selectivity over CDK2 and Chk2, respectively.

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.

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

CHIR-124 is a potent and selective Chk1 inhibitor with IC₅₀ of 0.3 nM, and also potently targets PDGFR and FLT3 with IC₅₀s of 6.6 nM and 5.8 nM.

PF 477736 (PF 00477736) is a potent, selective and ATP-competitive inhibitor of Chk1, with a K_i of 0.49 nM, it is also a Chk2 inhibitor, with a K_i of 47 nM. PF 477736 shows <100-fold selectivity for Chk1 over VEGFR2, Fms, Yes, Aurora-A, FGFR3, Flt3, and Ret (IC₅₀=8 (K_i), 10, 14, 23, 23, 25, and 39 nM, respectively). PF 477736 can enhance Gemcitabine antitumor activity in vitro and in vivo.

Prexasertib dihydrochloride (LY2606368 dihydrochloride) 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 dihydrochloride inhibits CHK2 (IC₅₀=8 nM) and RSK1 (IC₅₀=9 nM). Prexasertib dihydrochloride causes double-stranded DNA breakage and replication catastrophe resulting in apoptosis. Prexasertib dihydrochloride shows potent anti-tumor activity.

PD 407824 is a checkpoint kinase Chk1 and WEE1 inhibitor with IC₅₀s of 47 and 97 nM, respectively. PD 407824 is a chemical BMP sensitizer and increases the sensitivity of cells to sub-threshold amounts of BMP4.

SB-218078 is a potent, selective, ATP-competitive and cell-permeable checkpoint kinase 1 (Chk1) inhibitor that inhibits Chk1 phosphorylation of cdc25C with an IC₅₀ of 15 nM. SB-218078 is less potently inhibits Cdc2 (IC₅₀ of 250 nM) and PKC (IC₅₀ of 1000 nM). SB-218078 causes apoptosis by DNA damage and cell cycle arrest.

Prexasertib dimesylate (LY2606368 dimesylate) 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 dimesylate inhibits CHK2 (IC₅₀=8 nM) and RSK1 (IC₅₀=9 nM). Prexasertib dimesylate causes double-stranded DNA breakage and replication catastrophe resulting in apoptosis. Prexasertib dimesylate shows potent anti-tumor activity.

CCT244747 is a potent, orally bioavailable and highly selective CHK1 inhibitor, with an IC₅₀ of 7.7 nM; CCT244747 also abrogates G2 checkpoint with an IC₅₀ of 29 nM.

GDC-0425 (RG-7602) is an orally available, highly selective small molecule ChK1 inhibitor. GDC-0425 can be used for the research of various malignancies.

GDC-0575 dihydrochloride (ARRY-575 dihydrochloride) is an orally bioavailable CHK1 inhibitor, with an IC₅₀ of 1.2 nM, and has antitumor activity.

SAR-020106 is an ATP-competitive, potent, and selective CHK1 inhibitor with an IC₅₀ of 13.3 nM for human CHK1. SAR-020106 shows excellent selectivity over CHK2. SAR-020106 significantly enhances the cell killing of Gemcitabine and SN38 by 3- to 29-fold in several colon tumor lines and in a p53-dependent fashion. SAR-020106 can enhance antitumor activity with selected anticancer agents.

Chk1-IN-5 is a potent checkpoint kinase 1 (Chk1) inhibitor. Chk1-IN-5 inhibits Chk1 phosphorylation and inhibits tumor growth in colon cancer xenograft model.

GNE-900 is a an ATP-competitive, selective, and orally active ChK1 inhibitor with IC₅₀s of 0.0011, 1.5 μM for ChKl, ChK2, respectively. GNE-900 abrogates the G2-M checkpoint, enhances DNA damage, and induces Apoptosis. Gemcitabine (HY-17026) and GNE-900 administration shows anti-tumor activity.