target
Description
Checkpoint kinase 1 (Chk1) regulates S and G
2-M phase cell cycle checkpoints in response to DNA damage. PF-477736 is an ATP-competitive inhibitor of Chk1 with a K
i value of 0.49 nM that demonstrates 100-fold selectivity over Chk2. When used in combination with various chemotherapeutics, PF-477736 abrogates DNA damage-induced cell cycle arrest, potentiating the antiproliferative effects of these compounds in tumor cell lines and xenografts.
Uses
Checkpoint kinase 1 (Chk1) regulates S and G2-M phase cell cycle checkpoints in response to DNA damage. PF-477736 is an ATP-competitive inhibitor of Chk1 with a Ki value of 0.49 nM that demonstrates 100-fold selectivity over Chk2. When used in combination with various chemotherapeutics, PF-477736 abrogates DNA damage-induced cell cycle arrest, potentiating the antiproliferative effects of these compounds in tumor cell lines and xenografts.[Cayman Chemical]
Uses
PF-477736 has been used as a checkpoint protein 1 (CHK1) inhibitor to study the effect of CHK1 in cell cycle regulation in primary breast and lung primary epithelial cells.
Uses
P293850 is a selective checkpoint kinase 1 (Chk1) inhibitor (Ki values are 0.49 and 47 nM for Chk1 and Chk2 respectively). Abrogates cell cycle arrest at S and G2-M checkpoints; sensitizes cells to DNA damage.
Definition
ChEBI: PF-00477736 is a diazepinoindole that is 8-amino-4,5-dihydro-6H-[1,2]diazepino[4,5,6-cd]indol-6-one which is substituted at position 2 by a 1-methylpyrazol-4-yl group and in which the amino group at position 8 has undergone condensation with the carboxy group of (2R)-2-cyclohexylglycine to give the corresponding carboxamide. It is an inhibitor of checkpoint kinase 1 (Chk 1). It has a role as an EC 2.7.11.1 (non-specific serine/threonine protein kinase) inhibitor and an antineoplastic agent. It is an amino acid amide, a member of pyrazoles and a diazepinoindole.
Biochem/physiol Actions
PF-477736 may be effectively used to resensitize platinum resistant ovarian cancer cells. PF-477736 alone or in combination with other chemotherapeutic agents may be used to treat triple-negative breast cancer.
References
[1] blasina a1, hallin j, chen e, arango me, kraynov e, register j, grant s, ninkovic s, chen p, nichols t, o'connor p, anderes k. breaching the dna damage checkpoint via pf-00477736, a novel small-molecule inhibitor of checkpoint kinase 1. mol cancer ther. 2008 aug;7(8):2394-404.
