Compounds that abrogate DNA-damage-induced cell cycle G2 checkpoint and/or augment the anti-cancer activity of DNA damaging treatments
AssigneeCanBas Co., Ltd.
InventorsTakumi Kawabe, Hidetaka Kobayashi
Life of this patent
Estimating the term…
Abstract
The invention provides compositions and methods to inhibit the cell cycle G2 checkpoint, in particular the DNA-damage-induced G2 checkpoint, in mammalian cells including human cells. Specifically, the invention provides compositions and methods to sensitize cells to DNA-damaging agents by abrogating the cell cycle G2 checkpoint. Compounds of the invention are used to treat proliferative disorders such as cancer. The invention provides compositions and methods for selectively sensitizing G1 checkpoint impaired cancer cells to DNA-damaging agents and treatments.
Claims28
A compound that abrogates the cell cycle G2 checkpoint when administered to a cell, wherein the compound has following structure:
- where either or both of benzene are substituted with pyrazine, pyrimidine, piperazine, morpholine, cyclohexane, piperizine or pyridine;
- R1 is a halogen, bromine (Br), chlorine (Cl), fluorine (F), iodine (I), amino (NH2), nitro (NO2), hydroxy (OH), O-methyl (OCH3), or methyl (CH3);
- R2, R3, R4, R5 and R6 is bromine (Br), chlorine (Cl), fluorine (F), iodine (I), amino (NH2), nitro (NO2), methyl (CH3), O-methyl (OCH3), hydroxy (OH), CH(CH3)2, CHO, CHOCH3, O(CH2)nCH3, OCO(C6H12)Cl, COOCH3 or hydrogen;
- X1 is nitrogen (NH), oxygen (O) or sulfate (S);
- and X2 is oxygen (O) or sulfate (S).
A method of abrogating the G2 checkpoint in a cell, comprising administering to a cell at least one compound having following structure:
- where either or both of benzene are substituted with pyrazine, pyrimidine, piperazine, morpholine, cyclohexane, piperizine or pyridine;
- R1 is a halogen, bromine (Br), chlorine (Cl), fluorine (F), iodine (I), amino (NH2), nitro (NO2), hydroxy (OH), O-methyl (OCH3), methyl (CH3) or hydrogen (H):
- R2, R3, R4, R5 and R6 is bromine (Br), chlorine (Cl), fluorine (F), iodine (I), amino (NH2), nitro (NO2), methyl (CH3), O-methyl (OCH3), hydroxy (OH), CH(CH3)2, CHO, CHOCH3, O(CH2)nCH3, OCO(C6H12)Cl, COOCH3 or hydrogen;
- X1 is nitrogen (NH), oxygen (O), or sulfate (S);
- and X2 is oxygen (0) or sulfate (S) in an amount effective to inhibit the G2 checkpoint.
Dependencies are inferred from the claim text.