Combination of a purine-based cdk inhibitor with a tyrosine kinase inhibitor and use thereof in the treatment of proliferative disorders

A pharmaceutical product comprising (i) an ErbB inhibitor;

• and (ii) a CDK inhibitor, or a pharmaceutically acceptable salt thereof, selected from:
• (a) roscovitine;
• (b) 3-{9-isopropyl-6-[(pyridin-3-ylmethyl)-amino]-9H-purin-2-ylamino}-2-methyl-pentan-2-ol;
• (c) 3-{9-isopropyl-6-[(pyridin-3-ylmethyl)-amino]-9H-purin-2-ylamino}-pentan-2-ol;
• and (d) (2R,3S-3-(6-((4,6-dimethylpyridin-3-ylmethylamino)-9-isopropyl-9H-purin-2-ylamino)pentan-2-ol as a combined preparation for simultaneous, sequential or separate use in therapy.

A method of treating a proliferative disorder, said method comprising simultaneously, sequentially or separately administering to a subject (i) an ErbB inhibitor;

• and (ii) a CDK inhibitor, or a pharmaceutically acceptable salt thereof, selected from:
• (a) roscovitine;
• (b) 3-{9-isopropyl-6-[(pyridin-3-ylmethyl)-amino]-9H-purin-2-ylamino}-2-methyl-pentan-2-ol;
• (c) 3-{9-isopropyl-6-[(pyridin-3-ylmethyl)-amino]-9H-purin-2-ylamino}-pentan-2-ol;
• and (d) (2R,3S-3-(6-((4,6-dimethylpyridin-3-ylmethylamino)-9-isopropyl-9H-purin-2-ylamino)pentan-2-ol.

A method of treating non-small cell lung cancer (NSCLC), said method comprising simultaneously, sequentially or separately administering to a subject (i) an ErbB inhibitor;

• and (ii) a CDK inhibitor, or a pharmaceutically acceptable salt thereof, selected from:
• (a) roscovitine;
• (b) 3-{9-isopropyl-6-[(pyridin-3-ylmethyl)-amino]-9H-purin-2-ylamino}-2-methyl-pentan-2-ol;
• (c) 3-{9-isopropyl-6-[(pyridin-3-ylmethyl)-amino]-9H-purin-2-ylamino}-pentan-2-ol;
• and (d) (2R,3S-3-(6-((4,6-dimethylpyridin-3-ylmethylamino)-9-isopropyl-9H-purin-2-ylamino)pentan-2-ol.

A kit of parts comprising:

• (i) an ErbB inhibitor;
• and
• (ii) a CDK inhibitor, or a pharmaceutically acceptable salt thereof, selected from:
• (a) roscovitine;
• (b) 3-{9-isopropyl-6-[(pyridin-3-ylmethyl)-amino]-9H-purin-2-ylamino}-2-methyl-pentan-2-ol;
• (c) 3-{9-isopropyl-6-[(pyridin-3-ylmethyl)-amino]-9H-purin-2-ylamino}-pentan-2-ol;
• and (d) (2R,3S-3-(6-((4,6-dimethylpyridin-3-ylmethylamino)-9-isopropyl-9H-purin-2-ylamino)pentan-2-ol.

A combination comprising (i) an ErbB inhibitor;

• and (ii) a compound of formula I, or a pharmaceutically acceptable salt thereof,
• wherein:
• R1 and R2 are each independently H or alkyl;
• R3 and R4 are each independently H, alkyl or aryl;
• R5 is alkyl or cycloalkyl, each of which may be optionally substituted with one or more OH groups;
• R6, R7, R8 and R9 are each independently H, alkyl, haloalkyl, halogen, NO2, OH, OMe, CN, NH2, COOH, CONH2, or SO2NH2.