Title |
A novel multi-CDK inhibitor P1446A-05 restricts melanoma growth and produces synergistic effects in combination with MAPK pathway inhibitors
|
---|---|
Published in |
Cancer Biology and Therapy, January 2016
|
DOI | 10.1080/15384047.2016.1139267 |
Pubmed ID | |
Authors |
Philip Eliades, David M. Miller, Benchun Miao, Raj Kumar, Michael Taylor, Shama Buch, Sreesha P. Srinivasa, Keith T. Flaherty, Hensin Tsao |
Abstract |
Nearly 100% of melanomas have a defect in the p16(INK4A):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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 1 | 100% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Science communicators (journalists, bloggers, editors) | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 16 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 6 | 38% |
Student > Ph. D. Student | 3 | 19% |
Student > Bachelor | 2 | 13% |
Lecturer | 1 | 6% |
Student > Postgraduate | 1 | 6% |
Other | 0 | 0% |
Unknown | 3 | 19% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 5 | 31% |
Pharmacology, Toxicology and Pharmaceutical Science | 3 | 19% |
Agricultural and Biological Sciences | 3 | 19% |
Biochemistry, Genetics and Molecular Biology | 1 | 6% |
Unknown | 4 | 25% |