Checkpoint Kinases (Chk) are protein kinases that are involved in cell cycle control. Two checkpoint kinase subtypes have been identified, Chk1 and Chk2. Chk1 is a central component of genome surveillance pathways and is a key regulator of the cell cycle and cell survival. Chk1 is required for the initiation of DNA damage checkpoints and has recently been shown to play a role in the normal (unperturbed) cell cycle. Chk1 impacts various stages of the cell cycle including the S phase, G2/M transition and M phase. In addition to mediating cell cycle checkpoints, Chk1 also contributes to DNA repair processes, gene transcription, embryo development, cellular responses to HIV infection and somatic cell viability. Chk2 is a protein kinase that is activated in response to DNA damage and is involved in cell cycle arrest. In response to DNA damage and replication blocks, cell cycle progression is halted through the control of cell cycle regulators. The protein encoded by this gene is a cell cycle checkpoint regulator and putative tumor suppressor.
||AZD-7762 is a potent ATP-competitive checkpoint kinase (Chk) inhibitor in with IC50 of 5 nM for Chk1.
||SCH900776 is a potent, selective and orally bioavailable inhibitor of checkpoint kinase1 (Chk1) with IC50 of 3 nM, and has much greater selectivity than Chk2 (IC50=1500 nM) and cyclin-dependent kinase CDK2 (IC50=160 nM).
||LY2606368 is a potent and selective ATP competitive inhibitor of the Chk1 protein kinase, with IC50s of <1 nM and 8 nM for CHK1 and CHK2, respectively, and a Ki of 0.9 nM against purified CHK1.
||CCT244747 is a potent, orally bioavailable and highly selective CHK1 inhibitor, with an IC50 of 7.7 nM; also abrogates G2 checkpoint with an IC50 of 29 nM.
||LY2603618 is a potent and selective inhibitor of Chk1 protein kinase activity in vitro with IC50 of 7 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 is a potent, selective ATP-competitive inhibitor of Chk1, with a Ki of 0.49 nM, 100-fold selectivity versus Chk2 (Ki, 47 nM).
||Prexasertib (LY2606368) 2HCl
||LY2606368 dihydrochloride is a potent and selective ATP competitive inhibitor of the Chk1 protein kinase, with IC50s of <1 nM and 8 nM for CHK1 and CHK2, respectively, and a Ki of 0.9 nM against purified CHK1.
||CCT241533 is a potent and selective ATP competitive inhibitor of CHK2 with an IC50 of 3 nM and Ki of 1.16 nM.
||CCT241533 hydrochloride is a potent and selective ATP competitive inhibitor of CHK2 with an IC50 of 3 nM and Ki of 1.16 nM.
||CCT245737 is a orally active and seletive Chk1 inhibitor, with an IC50 of 1.3 nM; shows much less activity against Chk2, with an IC50 of 2440 nM.
||BML-277 is a selective checkpoint kinase 2 (Chk2) inhibitor with an IC50 of 15 nM.
||GDC0575（ARRY-575，RG7441）is a small molecule inhibitor of cell cycle checkpoint kinase 1 (Chk1), with potential chemosensitization activity.
||SB218078 is an inhibitor of checkpoint kinase 1 (Chk1) that displays selectivity over other protein kinases (IC50 values are 15, 250 and 1000 nM for Chk1, cdc2 and PKC respectively).
||A potent and selective Chk2 inhibitor with Ki/IC50 of 11 nM/120 nM.
||A potent, selective, reversible, ATP-competitive Chk2 inhibitor with IC50 of 0.2 uM.
||A potent, specific, orally available, ATP‑competitive inhibitor of Chk1 and Chk2 with Ki of 2.2 nM and 0.07 nM, respectively.
||BAY-1816032 is a highly potent, selective, orally active BUB1 mitotic checkpoint serine/threonine kinase with IC50 of 7 nM, displays excellent selectivity on a panel of 395 kinases.
||A potent, selective, ATP-competitive Chk1 inhibitor with IC50 of 13.3 nM.
||A potent, selective and orally active Chk1 inhibitor.
||GNE-900 (GNE900) is a potent, selective, ATP-competitive, and orally bioavailable Chk1 inhibitor with IC50 of <1 nM.
||GDC-0575 (ARRY-575, RG-7741) is a potent, selective and orally bioavailable Chk1 inhibitor with IC50 of 1.2 nM.
||A potent, selective, ATP-competitive Chk1 and Chk2 inhibitor with IC50 of 4.4 nM and 4.5 nM, respectively.
||A potent, selective, orally active Chk1 inhibitor with IC50 of < 1 nM, Ki=69 pM.
||A potent, ATP-competitive and highly selective Chk2 inhibitor with IC50 of 138 nM.
||A potent, reasonably selective Chk1 inhibitor with cell IC50 of 5 nM
||A marine sponge alkaloid that inhibits Chk1 and Chk2 with IC50 of 3 and 3.5 uM, respectively
||A novel potent, selective CHK1 inhibitor 2 nM, >80-fold selectivity over CHK2