GPBP-1 inhibition and its therapeutic use
AssigneesFibrostein, S.L., Universitat De Valencia
InventorsJuan Saus, Francisco Revert-Ros, Fernando Revert, Carmen Aguado-Velasco, Ernesto López-Pascual, Alejandra María Pérez-Sastre, Raúl Blasco, Héctor Pérez-Montoyo
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Abstract
The present invention provides compositions including anti-tumor agents and inhibitors of Goodpasture antigen binding protein, p21, and ABCC7, and their use in treating cancer.
Claims35
A pharmaceutical composition, comprising:
- (a) an antitumor drug or a pharmaceutically acceptable salt thereof, wherein the antitumor drug is selected from the group consisting of paclitaxel, a topoisomerase II inhibitor, 5-fluorouracil (5-FU), and cisplatin;
- (b) a compound of formula:
- or a pharmaceutically acceptable salt thereof, wherein:
- R is selected from N and CR3;
- R1 is hydrogen or C1-C6 alkoxy;
- R2 is C1-C6 alkyl or halo(C1-C6 alkyl);
- R3, if present, is halogen, C1-C6 alkyl, or halo(C1-C6 alkyl);
- and
- R4 is H or C1-C6 alkyl;
- and
- (c) a pharmaceutically acceptable carrier.
A method of treating a tumor, comprising administering to a subject with a tumor an amount effective to treat the tumor of:
- (a) an antitumor drug or a pharmaceutically acceptable salt thereof, wherein the antitumor drug is selected from the group consisting of paclitaxel, a topoisomerase II inhibitor, 5-fluorouracil (5-FU), and cisplatin;
- and
- (b) a compound of formula:
- or a pharmaceutically acceptable salt thereof, wherein:
- R is selected from N and CR3;
- R1 is hydrogen or C1-C6 alkoxy;
- R2 is C1-C6 alkyl or halo(C1-C6 alkyl);
- R3, if present, is halogen, C1-C6 alkyl, or halo(C1-C6 alkyl);
- and
- R4 is H or C1-C6 alkyl.
A method for treating a tumor, comprising administering to a subject with a tumor an amount effective to treat the tumor of
- (a) an antitumor drug, wherein the antitumor drug is selected from the group consisting of paclitaxel, a topoisomerase II inhibitor, 5-fluorouracil (5-FU), and cisplatin;
- and
- (b) a GPBP-1 inhibitor.
A method for reducing chemoresistance of a tumor, comprising administering to a subject with a tumor that is to be treated with a chemotherapeutic an amount effective of an inhibitor of ATP-binding cassette transporter 7 (ABCC7), or a pharmaceutically acceptable salt thereof, to inhibit ABCC7 expression and/or activity in the tumor.
A compound of formula:
- or a pharmaceutically acceptable salt thereof, wherein:
- R is selected from N and CR3;
- R3 is selected from the group consisting of hydrogen, halogen, cyano, nitro, hydroxy, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, halo(C1-C6 alkyl), C1-C6 alkoxy, halo(C1-C6 alkoxy), amino, (C1-C6 alkyl)amino, di(C1-C6 alkyl)amino, hydroxy(C1-C6 alkyl), (C1-C6 alkoxy)C1-C6 alkyl, amino(C1-C6 alkyl), sulfanyl(C1-C6 alkyl), (C1-C6 alkyl)sulfanyl(C1-C6 alkyl), —(CH2)1-5—C(O)(C1-C6 alkoxy), —(CH2)1-5—C(O)NH2, (aryl)C2-C6 alkyl, and (heteroaryl)C1-C6 alkyl;
- R1 is hydrogen, halogen, hydroxy, C1-C6 alkyl, halo(C1-C6 alkyl), C1-C6 alkoxy, halo(C1-C6 alkoxy), hydroxy(C1-C6 alkyl), (C1-C6 alkoxy)C1-C6 alkyl, amino(C1-C6 alkyl), sulfanyl(C1-C6 alkyl), or (C1-C6 alkyl)sulfanyl(C1-C6 alkyl);
- R2 is C1-C6 alkyl, halo(C1-C6 alkyl), C1-C6 alkoxy, halo(C1-C6 alkoxy), hydroxy(C1-C6 alkyl), (C1-C6 alkoxy)C1-C6 alkyl, formyl(C1-C6 alkyl), amino(C1-C6 alkyl), sulfanyl(C1-C6 alkyl), (C1-C6 alkyl)sulfanyl(C1-C6 alkyl), —(CH2)1-5—C(O)OH, —(CH2)1-5—C(O)(C1-C6 alkoxy), —(CH2)1-5—C(O)NH2, —(CH2)1-5—C(O)NH(C1-C6 alkyl), —(CH2)1-5—C(O)N(C1-C6 alkyl)2, —CH═CH—C(O)OH, or —CH═CH—C(O)(C1-C6 alkoxy);
- and
- R4 is hydrogen, C1-C6 alkyl, or (aryl)C1-C6 alkyl.
A method for reducing chemoresistance of a tumor, comprising administering to a subject with a tumor that is to be treated with a chemotherapeutic an amount effective of an inhibitor of p21, or a pharmaceutically acceptable salt thereof, to inhibit p21 expression and/or activity in the tumor.
A compound of the formula
- or a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.