Seliciclib | roscovitine | CYC202 | CAS#186692-46-6 | CDK inhibitor

MedKoo Cat#: 202580 | Name: Seliciclib (Roscovitine)

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Seliciclib, also known as roscovitine and CYC202, is a n orally bioavailable, small-molecule cyclin-dependent kinase (CDK) inhibitor with potential proapoptotic and antineoplastic activities. Seliciclib primarily inhibits CDK2/E, CDK2/A, CDK7 and CDK9 by competing for their ATP binding sites, leading to a disruption of cell cycle progression. In addition, this agent appears to interfere with CDK-mediated phosphorylation of the carboxy-terminal domain of RNA polymerase II, inhibiting RNA polymerase II-dependent transcription, which may result in the down-regulation of antiapoptotic proteins such as induced myeloid leukemia cell differentiation protein Mcl-1.

Chemical Structure

Seliciclib (Roscovitine)

CAS#186692-46-6

Theoretical Analysis

MedKoo Cat#: 202580

Name: Seliciclib (Roscovitine)

CAS#: 186692-46-6

Chemical Formula: C19H26N6O

Exact Mass: 354.2168

Molecular Weight: 354.44

Elemental Analysis: C, 64.38; H, 7.39; N, 23.71; O, 4.51

Price and Availability

Size	Price	Availability
5mg	USD 150.00	Ready to ship
10mg	USD 250.00	Ready to ship
25mg	USD 500.00	Ready to ship
50mg	USD 850.00	Ready to ship
100mg	USD 1,450.00	Ready to ship

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Synonym

CYC202; CYC202; CYC 202; R-Roscovitine; Roscovitin; Roscovitine; Seliciclib.

IUPAC/Chemical Name

(R)-2-((6-(benzylamino)-9-isopropyl-9H-purin-2-yl)amino)butan-1-ol

InChi Key

BTIHMVBBUGXLCJ-OAHLLOKOSA-N

InChi Code

InChI=1S/C19H26N6O/c1-4-15(11-26)22-19-23-17(20-10-14-8-6-5-7-9-14)16-18(24-19)25(12-21-16)13(2)3/h5-9,12-13,15,26H,4,10-11H2,1-3H3,(H2,20,22,23,24)/t15-/m1/s1

SMILES Code

CC[C@@H](NC1=NC(NCC2=CC=CC=C2)=C3N=CN(C(C)C)C3=N1)CO

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Phase I trial of Selicilib: Fifty-six patients received a total of 218 cycles of seliciclib. Dose-Limiting Toxicities (DLT) consisting of nausea, vomiting, asthenia and hypokalaemia occurred at 1600 mg bid for schedule A and in schedule C, DLT of hypokalaemia and asthenia occurred at 1800 mg bid. The evaluation of longer treatment duration in schedule B was discontinued because of unacceptable toxicity at lower doses. Other adverse events included transient serum creatinine increases and liver dysfunctions. Pharmacokinetic data showed that exposure to seliciclib and its carboxylate metabolite increased with increasing dose. Soluble cytokeratin 18 fragments allowed monitoring of seliciclib-induced cell death in the blood of patients treated with seliciclib at doses above 800 mg/d. One partial response in a patient with hepatocellular carcinoma and sustained tumour stabilisations were observed. The MTD and RD for seliciclib are 1250 mg bid for 5d every 3 weeks and 1600 mg bid for 3d every 2 weeks, respectively. ( Eur J Cancer. 2010 Dec;46(18):3243-50. ).

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#C21R04B09

QC Data

View QC data: current batch, Lot#C21R04B09

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

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.

In vitro activity:

Seliciclib strongly enhanced the effect of olaparib on radiosensitivity for human Papillomavirus (HPV) negative head and neck squamous cell carcinoma (HNSCC) cell lines. In all five HPV negative and HPV positive cell lines tested, seliciclib caused inhibition of CDK1 and 2. For HPV negative cell lines, treatment with seliciclib resulted in a pronounced enhancement of the radiation-induced G2 arrest as well as a significant increase in radiosensitivity. Reference: Oncotarget. 2017 Oct 24;8(62):105170-105183. https://pubmed.ncbi.nlm.nih.gov/29285242/

In vivo activity:

This study found that seliciclib worsened Mycobacterium abscessus infection by reducing DUOX2-mediated neutrophil response, which may have significant therapeutic implications for safely targeting inflammation in cystic fibrosis. In zebrafish, seliciclib exerted anti-inflammatory and proresolution effects in neutrophilic inflammation induced by infection or tail amputation. While seliciclib enhanced intracellular bacterial killing of M. abscessus in human CF macrophages ex vivo, in vivo treatment worsened infection. Reference: Am J Respir Cell Mol Biol. 2022 Apr;66(4):439-451. https://pubmed.ncbi.nlm.nih.gov/35081328/

	Solvent	mg/mL	mM
Solubility
	DMSO	71.0	200.31
	Ethanol	71.0	200.31

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 354.44 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Huang Q, Zhong Y, Li J, Ye Y, Wu W, Chen L, Feng M, Yang J, Liu S. Kinase inhibitor roscovitine as a PB2 cap-binding inhibitor against influenza a virus replication. Biochem Biophys Res Commun. 2020 Jun 11;526(4):1143-1149. doi: 10.1016/j.bbrc.2020.04.034. Epub 2020 Apr 13. PMID: 32327257; PMCID: PMC7152910. 2. Ziemann F, Seltzsam S, Dreffke K, Preising S, Arenz A, Subtil FSB, Rieckmann T, Engenhart-Cabillic R, Dikomey E, Wittig A. Roscovitine strongly enhances the effect of olaparib on radiosensitivity for HPV neg. but not for HPV pos. HNSCC cell lines. Oncotarget. 2017 Oct 24;8(62):105170-105183. doi: 10.18632/oncotarget.22005. PMID: 29285242; PMCID: PMC5739629. 3. Moëlo C, Quillévéré A, Le Roy L, Timsit S. (S)-roscovitine, a CDK inhibitor, decreases cerebral edema and modulates AQP4 and α1-syntrophin interaction on a pre-clinical model of acute ischemic stroke. Glia. 2023 Oct 13. doi: 10.1002/glia.24477. Epub ahead of print. PMID: 37828900. 4. Le Moigne V, Rodriguez Rincon D, Glatigny S, Dupont CM, Langevin C, Ait Ali Said A, Renshaw SA, Floto RA, Herrmann JL, Bernut A. Roscovitine Worsens Mycobacterium abscessus Infection by Reducing DUOX2-mediated Neutrophil Response. Am J Respir Cell Mol Biol. 2022 Apr;66(4):439-451. doi: 10.1165/rcmb.2021-0406OC. PMID: 35081328; PMCID: PMC8990120.

In vitro protocol:

In vivo protocol:

1. Moëlo C, Quillévéré A, Le Roy L, Timsit S. (S)-roscovitine, a CDK inhibitor, decreases cerebral edema and modulates AQP4 and α1-syntrophin interaction on a pre-clinical model of acute ischemic stroke. Glia. 2023 Oct 13. doi: 10.1002/glia.24477. Epub ahead of print. PMID: 37828900. 2. Le Moigne V, Rodriguez Rincon D, Glatigny S, Dupont CM, Langevin C, Ait Ali Said A, Renshaw SA, Floto RA, Herrmann JL, Bernut A. Roscovitine Worsens Mycobacterium abscessus Infection by Reducing DUOX2-mediated Neutrophil Response. Am J Respir Cell Mol Biol. 2022 Apr;66(4):439-451. doi: 10.1165/rcmb.2021-0406OC. PMID: 35081328; PMCID: PMC8990120.

1: Khalil HS, Mitev V, Vlaykova T, Cavicchi L, Zhelev N. Discovery and development of Seliciclib. How systems biology approaches can lead to better drug performance. J Biotechnol. 2015 Mar 6. pii: S0168-1656(15)00094-2. doi: 10.1016/j.jbiotec.2015.02.032. [Epub ahead of print] PubMed PMID: 25747275. 2: Jackson RC, Radivoyevitch T. Modelling c-Abl Signalling in Activated Neutrophils: the Anti-inflammatory Effect of Seliciclib. Biodiscovery. 2013 Mar 1;7(4):4. PubMed PMID: 24765523; PubMed Central PMCID: PMC3994723. 3: Nutter F, Khwaja A, Haylor J. Seliciclib inhibits renal hypertrophy but not fibrosis in the rat following subtotal nephrectomy. Nephron Exp Nephrol. 2012;122(3-4):114-22. doi: 10.1159/000350248. Epub 2013 May 8. PubMed PMID: 23689642. 4: Josefsberg Ben-Yehoshua L, Beider K, Shimoni A, Ostrovsky O, Samookh M, Peled A, Nagler A. Characterization of cyclin E expression in multiple myeloma and its functional role in seliciclib-induced apoptotic cell death. PLoS One. 2012;7(4):e33856. doi: 10.1371/journal.pone.0033856. Epub 2012 Apr 25. PubMed PMID: 22558078; PubMed Central PMCID: PMC3338814. 5: Coley HM, Safuwan NA, Chivers P, Papacharalbous E, Giannopoulos T, Butler-Manuel S, Madhuri K, Lovell DP, Crook T. The cyclin-dependent kinase inhibitor p57(Kip2) is epigenetically regulated in carboplatin resistance and results in collateral sensitivity to the CDK inhibitor seliciclib in ovarian cancer. Br J Cancer. 2012 Jan 31;106(3):482-9. doi: 10.1038/bjc.2011.566. Epub 2012 Jan 10. PubMed PMID: 22233925; PubMed Central PMCID: PMC3273354. 6: Sheryanna AM, Smith J, Bhangal G, Barnett A, McClue S, Tam FW, Cook T, Pusey CD. Treatment with a cyclin-dependent kinase inhibitor, seliciclib, is effective in reducing glomerular macrophage numbers and the severity of established experimental glomerulonephritis. Nephrology (Carlton). 2011 May;16(4):410-6. doi: 10.1111/j.1440-1797.2010.01416.x. PubMed PMID: 21518118. 7: Le Tourneau C, Faivre S, Laurence V, Delbaldo C, Vera K, Girre V, Chiao J, Armour S, Frame S, Green SR, Gianella-Borradori A, DiÃ©ras V, Raymond E. Phase I evaluation of seliciclib (R-roscovitine), a novel oral cyclin-dependent kinase inhibitor, in patients with advanced malignancies. Eur J Cancer. 2010 Dec;46(18):3243-50. doi: 10.1016/j.ejca.2010.08.001. Epub 2010 Sep 6. PubMed PMID: 20822897. 8: Rajnai Z, MÃ©hn D, BeÃ©ry E, Okyar A, Jani M, TÃ³th GK, FÃ¼lÃ¶p F, LÃ©vi F, Krajcsi P. ATP-binding cassette B1 transports seliciclib (R-roscovitine), a cyclin-dependent kinase inhibitor. Drug Metab Dispos. 2010 Nov;38(11):2000-6. doi: 10.1124/dmd.110.032805. Epub 2010 Aug 10. PubMed PMID: 20699410. 9: Federico M, Symonds CE, Bagella L, Rizzolio F, Fanale D, Russo A, Giordano A. R-Roscovitine (Seliciclib) prevents DNA damage-induced cyclin A1 upregulation and hinders non-homologous end-joining (NHEJ) DNA repair. Mol Cancer. 2010 Aug 4;9:208. doi: 10.1186/1476-4598-9-208. PubMed PMID: 20684776; PubMed Central PMCID: PMC3224749. 10: Aldoss IT, Tashi T, Ganti AK. Seliciclib in malignancies. Expert Opin Investig Drugs. 2009 Dec;18(12):1957-65. doi: 10.1517/13543780903418445. PubMed PMID: 19938906. 11: Rogalińska M, Błoński JZ, Komina O, GÃ³ralski P, Zołnierczyk JD, Piekarski H, Robak T, Kiliańska ZM, Wesierska-Gadek J. R-roscovitine (Seliciclib) affects CLL cells more strongly than combinations of fludarabine or cladribine with cyclophosphamide: Inhibition of CDK7 sensitizes leukemic cells to caspase-dependent apoptosis. J Cell Biochem. 2010 Jan 1;109(1):217-35. doi: 10.1002/jcb.22400. PubMed PMID: 19911397. 12: Iurisci I, Filipski E, Sallam H, Harper F, Guettier C, Maire I, Hassan M, Iacobelli S, LÃ©vi F. Liver circadian clock, a pharmacologic target of cyclin-dependent kinase inhibitor seliciclib. Chronobiol Int. 2009 Aug;26(6):1169-88. doi: 10.3109/07420520903209942. PubMed PMID: 19731111. 13: Hui AB, Yue S, Shi W, Alajez NM, Ito E, Green SR, Frame S, O'Sullivan B, Liu FF. Therapeutic efficacy of seliciclib in combination with ionizing radiation for human nasopharyngeal carcinoma. Clin Cancer Res. 2009 Jun 1;15(11):3716-24. doi: 10.1158/1078-0432.CCR-08-2790. Epub 2009 May 26. PubMed PMID: 19470731. 14: Hsieh WS, Soo R, Peh BK, Loh T, Dong D, Soh D, Wong LS, Green S, Chiao J, Cui CY, Lai YF, Lee SC, Mow B, Soong R, Salto-Tellez M, Goh BC. Pharmacodynamic effects of seliciclib, an orally administered cell cycle modulator, in undifferentiated nasopharyngeal cancer. Clin Cancer Res. 2009 Feb 15;15(4):1435-42. doi: 10.1158/1078-0432.CCR-08-1748. PubMed PMID: 19228744. 15: Appleyard MV, O'Neill MA, Murray KE, Paulin FE, Bray SE, Kernohan NM, Levison DA, Lane DP, Thompson AM. Seliciclib (CYC202, R-roscovitine) enhances the antitumor effect of doxorubicin in vivo in a breast cancer xenograft model. Int J Cancer. 2009 Jan 15;124(2):465-72. doi: 10.1002/ijc.23938. PubMed PMID: 19003963. 16: Fleming IN, Hogben M, Frame S, McClue SJ, Green SR. Synergistic inhibition of ErbB signaling by combined treatment with seliciclib and ErbB-targeting agents. Clin Cancer Res. 2008 Jul 1;14(13):4326-35. doi: 10.1158/1078-0432.CCR-07-4633. PubMed PMID: 18594016. 17: Pezzotta A, Mister M, Monteferrante G, Cassis L, Azzollini N, Aiello S, Satta M, Benigni A, Remuzzi G, Noris M. Effect of seliciclib (CYC202, R-roscovitine) on lymphocyte alloreactivity and acute kidney allograft rejection in rat. Transplantation. 2008 May 27;85(10):1476-82. doi: 10.1097/TP.0b013e31816f240c. PubMed PMID: 18497689. 18: Jackson RC, Barnett AL, McClue SJ, Green SR. Seliciclib, a cell-cycle modulator that acts through the inhibition of cyclin-dependent kinases. Expert Opin Drug Discov. 2008 Jan;3(1):131-43. doi: 10.1517/17460441.3.1.131. PubMed PMID: 23480144. 19: Whittaker SR, Te Poele RH, Chan F, Linardopoulos S, Walton MI, Garrett MD, Workman P. The cyclin-dependent kinase inhibitor seliciclib (R-roscovitine; CYC202) decreases the expression of mitotic control genes and prevents entry into mitosis. Cell Cycle. 2007 Dec 15;6(24):3114-31. Epub 2007 Oct 5. PubMed PMID: 18075315. 20: McClue SJ, Stuart I. Metabolism of the trisubstituted purine cyclin-dependent kinase inhibitor seliciclib (R-roscovitine) in vitro and in vivo. Drug Metab Dispos. 2008 Mar;36(3):561-70. Epub 2007 Nov 29. PubMed PMID: 18048486.