Wednesday, April 20, 2016

P1446A-05 (a multi-CDK inhibitor) decreases melanoma growth especially when combined with MAPK inhibitors!

A novel multi-CDK inhibitor P1446A-05 restricts melanoma growth and produces synergistic effects in combination with MAPK pathway inhibitors.  Eliades, Miller, Miao, Flaherty, et al.  Cancer Biol Ther.  2016 Jan 25.

"Nearly 100% of melanomas have a defect in the p16INK4A:cyclin D-CDK4/6:RB pathway, leading to abnormal cell cycle control and unregulated cellular proliferation. Here, we report that P1446A-05, a novel multi-CDK inhibitor has significant inhibitory activity against cutaneous and uveal melanoma. Mechanistic studies revealed that P1446A-05 inhibits phosphorylation targets of CDK members, and induces cell cycle arrest and apoptosis irrespective of melanoma genotype or phenotype. Additionally, we show preclinical evidence that P1446A-05 can synergize with other small molecule inhibitors previously studied in melanoma. Collectively, these data demonstrate that targeting cell cycle and transcriptional CDKs with a small molecule multi-CDK inhibitor is a viable approach for developing novel anti-melanoma therapeutics."

If you are wondering where CDK falls in the molecular lay of things...this diagram may help:  Melanoma pathways: melanoma molecular disease model

Early days with this one to be sure...but every bit of a good new a good new thing!!! - c

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