(R)-Roscovitine  (Synonyms: Seliciclib; CYC202)

(R)-Roscovitine (Seliciclib) is an orally bioavailable and selective CDKs inhibitor with IC₅₀s of 0.2 μM, 0.65 μM, and 0.7 μM for CDK5, Cdc2, and CDK2, respectively.

(R)-Roscovitine (Seliciclib) displays high efficiency and high selectivity towards some cyclin-dependent kinases. The kinase specificity of Seliciclib is investigated with 25 highly purified kinases (including protein kinase A, G and C isoforms, myosin light-chain kinase, casein kinase 2, IR tyrosine kinase, c-src, v-abl). Most kinases are not significantly inhibited by (R)-Roscovitine. Cdc2, Cdk2, and Cdk5 only are substantially inhibited (IC₅₀ values of 0.65, 0.7, and 0.2 μM, respectively). Cdk4k and Cdk6 are very poorly inhibited by (R)-Roscovitine (IC₅₀>100 μM). Extracellular regulated kinases erk1 and erk2 are inhibited with an IC₅₀ of 34 μM and 14 μM, respectively. (R)-Roscovitine inhibits the proliferation of mammalian cell lines with an average IC₅₀ of 16 μM^[1]. (R)-Roscovitine (Seliciclib) decreases the level of CDK5 and p35 with upregulation of E-cadherin, but downregulation of Vimentin and Collagen IV. Moreover, (R)-Roscovitine inhibits the ability of high glucose cultured NRK52E cells to migrate and invade^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Compare with normal controls, (R)-Roscovitine (Seliciclib) downregulates phosphorylated ERK1/2 and PPARγ with concomitant increase in E-cadherin, but decrease in Vimentin and Collagen IV. Correspondingly, (R)-Roscovitine decreases renal tubulointerstitial fibrosis of diabetic rats. (R)-Roscovitine is effective in decreasing tubulointerstitial fibrosis via the ERK1/2/PPARγ pathway in diabetic rats^[2]. (R)-Roscovitine (Seliciclib) (16.5 mg/kg) significantly reduces the rate of tumor growth and increases survival of treated mice. Strikingly, (R)-Roscovitine treatment leads to complete tumor disappearance in one mouse (25%); moreover, no tumor regrowth in this mouse is found 5 months after completion of the treatment. Mouse weights do not differ significantly between mice treated with (R)-Roscovitine and control mice, and behavioral differences between the two groups are also negligible. These results suggest that (R)-Roscovitine can be used effectively as a selective tumor growth inhibitor in HPV+ head and neck cancer^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

354.45

C₁₉H₂₆N₆O

186692-46-6

Solid

White to off-white

OC[C@H](NC1=NC(NCC2=CC=CC=C2)=C3C(N(C=N3)C(C)C)=N1)CC

Room temperature in continental US; may vary elsewhere.

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 1 year; -20°C, 6 months. When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.

• [1]. Meijer L, et al. Biochemical and cellular effects of roscovitine, a potent and selective inhibitor of the cyclin-dependent kinases cdc2, cdk2 and cdk5. Eur J Biochem. 1997 Jan 15;243(1-2):527-36.  [Content Brief]

  [2]. Bai X, et al. CDK5 promotes renal tubulointerstitial fibrosis in diabetic nephropathy via erk1/2/pparγ pathway. Oncotarget. 2016 Apr 27.  [Content Brief]

  [3]. Gary C, et al. Selective antitumor activity of roscovitine in head and neck cancer. Oncotarget. 2016 May 23.  [Content Brief]