Roscovitine

Description

Roscovitine (186692-46-6) is a potent and selective inhibitor of cyclin-dependent kinases displaying higher potency and selectivity compared to olomoucine. p34 cdc2 IC50 = 0.2 μM. Also inhibits p33cdk2 and p33cdk5.1 Anti-angiogenic.2 Prevents PPARg S273 phosphorylation, promoting browning of white adipose tissue.3 Enhances peripheral nerve regrowth.4

Uses

Roscovitine is a potent and selective inhibitor of cyclin-dependent kinases (CDKs). Roscovitine has been found to produce apoptosis in treated cancerous cells of non-small cell lung cancer (NSCLC) and other cancers. Studies show that Roscovitine displays increased anti-mitotic activity at the G1/S and G2/M phases of the cell cycle. Roscovitine maybe useful in the treatment of non-small cell lung cancer (NSCLC), leukemia, HIV infection, herpes simplex infection, and the mechanisms of chronic inflammation disorders.

Definition

ChEBI: 2,6-Diaminopurine carrying benzylamino, (2R)-1-hydroxybutan-2-yl and isopropyl substituents at C-6, C-2-N and N-9 respectively. It is an experimental drug candidate in the family of pharmacological cyclin-dependent kinase (CDK) inhibitors.

General Description

A potent, reversible, and selective inhibitor of cyclin-dependent kinases (Cdks) that exhibits about ten-fold greater efficacy towards p34^cdk1 and p33^cdk2 and twenty-fold greater efficacy towards p33^cdk5 relative to Olomoucine (Cat. No. 495620). Inhibits p34^cdk1/cyclin B (IC₅₀ = 650 nM), p33^cdk2/cyclin A (IC₅₀ = 700 nM), p33^cdk2/cyclin E (IC₅₀ = 700 nM), and p33^cdk5/p35 (IC₅₀ = 200 nM) by competing for the ATP binding domain of the kinases. Exhibits reduced sensitivity towards related kinases including ERK1 and ERK2 (IC₅₀ = 34 μM and 14 μM, respectively). Roscovitine does not significantly affect the activity of other protein kinases even at 100 μM, including p34^cdk4/cyclin D1 and p40^cdk6/cyclin D2. Compared to olomoucine, roscovitine displays increased anti-mitotic activity at the G₁/S and G₂/M phases of the cell cycle. A 50 mM (5 mg/282 μl) solution of Roscovitine (Cat. No. 557364) in DMSO is also available.

Biochem/physiol Actions

Roscovitine is a purine derived inhibitor. It stimulates apoptosis in cancer cells. It has inhibitory action on mitogen activated protein kinase (MAPK) and M-phase promoting factor (MPF) kinase activity. Roscovitine is known to arrest meiosis and thus, prevent embryonic development.

Anticancer Research

Roscovitine a derivative of olomoucine which is isolated from Raphanus sativus isunder clinical trials (Shoeb 2006).

storage

Store at -20°C

References

[1] LAURENT MEIJER. Biochemical and Cellular Effects of Roscovitine, a Potent and Selective Inhibitor of the Cyclin-Dependent Kinases cdc2, cdk2 and cdk5[J]. The FEBS journal, 2004, 243 1-2: 527-536. DOI:10.1111/j.1432-1033.1997.t01-2-00527.x
[2] JOHANNA LIEBL. Anti-angiogenic effects of purine inhibitors of cyclin dependent kinases[J]. Angiogenesis, 2011, 14 3: 281-291. DOI:10.1007/s10456-011-9212-6
[3] HONG WANG. Browning of White Adipose Tissue with Roscovitine Induces a Distinct Population of UCP1+ Adipocytes.[J]. Cell metabolism, 2016, 24 6 1: 835-847. DOI:10.1016/j.cmet.2016.10.005
[4] V. LAW. Enhancement of Peripheral Nerve Regrowth by the Purine Nucleoside Analog and Cell Cycle Inhibitor, Roscovitine[J]. Frontiers in Cellular Neuroscience, 2016, 10 1. DOI:10.3389/fncel.2016.00238