Details of the Drug

General Information of Drug (ID: DMSH108)

Drug Name
R-roscovitine
Synonyms
Seliciclib; roscovitine; 186692-46-6; R-Roscovitine; (R)-roscovitine; CYC202; CYC-202; CYC 202; 2-(R)-(1-Ethyl-2-hydroxyethylamino)-6-benzylamino-9-isopropylpurine; UNII-0ES1C2KQ94; Roscovitine (Seliciclib,CYC202); NSC 701554; AL-39256; Roscovitine; CHEMBL14762; 0ES1C2KQ94; CHEBI:45307; NSC701554; NSC-701554; (2R)-2-[[6-(benzylamino)-9-isopropyl-purin-2-yl]amino]butan-1-ol; (R)-2-((6-(Benzylamino)-9-isopropyl-9H-purin-2-yl)amino)butan-1-ol; (2R)-2-[[6-(benzylamino)-9-propan-2-ylpurin-2-yl]amino]butan-1-ol; RRC; Rosco; M02443; BMK1-E12; CYC202, Seliciclib, R-roscovitine, Roscovitine; (2r)-2-{[6-(benzylamino)-9-isopropyl-9h-purin-2-yl]amino}-1-butanol; 2-(R)-[[9-(1-Methylethyl)-6-[(phenylmethyl)amino]-9H-purin-2-yl]amino]-1-butanol; 2-[[9-(1-Methylethyl)-6-[(phenylmethyl)amino]-9H-purin-2-yl]amino]-(R)-1-butanol; 6-(Benzylamino)-2(R)-[[1-(hydroxymethyl)propyl]amino]-9-isopropylpurine
Indication
Disease Entry ICD 11 Status REF
Non-small-cell lung cancer 2C25.Y Phase 2 [1]
Solid tumour/cancer 2A00-2F9Z Phase 2 [2]
Nasopharyngeal carcinoma 2B6B Investigative [3]
Affected Organisms
Humans and other mammals
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 354.4
Logarithm of the Partition Coefficient (xlogp) 3.2
Rotatable Bond Count (rotbonds) 8
Hydrogen Bond Donor Count (hbonddonor) 3
Hydrogen Bond Acceptor Count (hbondacc) 6
Chemical Identifiers
Formula
C19H26N6O
IUPAC Name
(2R)-2-[[6-(benzylamino)-9-propan-2-ylpurin-2-yl]amino]butan-1-ol
Canonical SMILES
CC[C@H](CO)NC1=NC(=C2C(=N1)N(C=N2)C(C)C)NCC3=CC=CC=C3
InChI
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
InChIKey
BTIHMVBBUGXLCJ-OAHLLOKOSA-N
Cross-matching ID
PubChem CID
160355
ChEBI ID
CHEMBL14762
CAS Number
186692-46-6
UNII
0ES1C2KQ94
DrugBank ID
DB06195
TTD ID
D05ADP
VARIDT ID
DR01494
INTEDE ID
DR1858
Drug-Molecule Activity Atlas (DMA)NEW Click to Jump to the Detailed DMA Information of This Drug
Drug Pharmacogenomic Perturbation (DPP)NEW Click to Jump to the Detailed DPP Information of This Drug
Drug ADMET Endpoint Profile (DAE)NEW Click to Jump to the Detailed DAE Information of This Drug
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug
Repurposed Drugs (RPD) Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Cyclin-dependent kinase (CDK) TTMBO1Z NOUNIPROTAC Inhibitor [3]
Cyclin-dependent kinase 1 (CDK1) TTH6V3D CDK1_HUMAN Inhibitor [4]
Cyclin-dependent kinase 2 (CDK2) TT7HF4W CDK2_HUMAN Inhibitor [4]
Cyclin-dependent kinase 7 (CDK7) TTQYF7G CDK7_HUMAN Inhibitor [4]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [5]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Substrate [6]
Cytochrome P450 2B6 (CYP2B6) DEPKLMQ CP2B6_HUMAN Substrate [6]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Baculoviral IAP repeat-containing protein 5 (BIRC5) OTILXZYL BIRC5_HUMAN Gene/Protein Processing [7]
Casein kinase I isoform delta (CSNK1D) OTNF4S77 KC1D_HUMAN Gene/Protein Processing [8]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Gene/Protein Processing [9]
Cytochrome c (CYCS) OTBFALJD CYC_HUMAN Protein Interaction/Cellular Processes [10]
Disabled homolog 2 (DAB2) OTRMQTMZ DAB2_HUMAN Post-Translational Modifications [11]
E3 ubiquitin-protein ligase XIAP OT24GP9B XIAP_HUMAN Gene/Protein Processing [10]
Retinoblastoma-associated protein (RB1) OTQJUJMZ RB_HUMAN Gene/Protein Processing [12]
Retinoblastoma-like protein 1 (RBL1) OTDEBFYC RBL1_HUMAN Gene/Protein Processing [13]
Serine/threonine-protein kinase PLK1 (PLK1) OTRZX45T PLK1_HUMAN Gene/Protein Processing [13]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Non-small-cell lung cancer
ICD Disease Classification 2C25.Y
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Cyclin-dependent kinase 1 (CDK1) DTT CDK1 5.27E-108 1.97 3.12
Cyclin-dependent kinase 2 (CDK2) DTT CDK2 2.28E-06 0.12 0.19
P-glycoprotein 1 (ABCB1) DTP P-GP 3.12E-33 -8.30E-01 -1.04E+00
Cytochrome P450 2B6 (CYP2B6) DME CYP2B6 2.81E-03 -9.34E-02 -3.57E-01
Cytochrome P450 3A4 (CYP3A4) DME CYP3A4 5.59E-39 -3.76E-01 -1.64E+00
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6035).
2 ClinicalTrials.gov (NCT02160730) Treatment of Cushing's Disease With R-roscovitine. U.S. National Institutes of Health.
3 Therapeutic efficacy of seliciclib in combination with ionizing radiation for human nasopharyngeal carcinoma.Clin Cancer Res. 2009 Jun 1;15(11):3716-24.
4 Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66.
5 ATP-binding cassette B1 transports seliciclib (R-roscovitine), a cyclin-dependent kinase inhibitor. Drug Metab Dispos. 2010 Nov;38(11):2000-6.
6 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.
7 Roscovitine is an effective inducer of apoptosis of Ewing's sarcoma family tumor cells in vitro and in vivo. Cancer Res. 2005 Oct 15;65(20):9320-7. doi: 10.1158/0008-5472.CAN-05-1276.
8 The specificities of protein kinase inhibitors: an update. Biochem J. 2003 Apr 1;371(Pt 1):199-204. doi: 10.1042/BJ20021535.
9 A bioinformatical and functional approach to identify novel strategies for chemoprevention of colorectal cancer. Oncogene. 2011 Apr 28;30(17):2026-36. doi: 10.1038/onc.2010.578. Epub 2011 Jan 10.
10 Accumulation of p53 and reductions in XIAP abundance promote the apoptosis of prostate cancer cells. Cancer Res. 2005 Sep 1;65(17):7717-23. doi: 10.1158/0008-5472.CAN-05-0347.
11 Cell cycle-dependent phosphorylation of Disabled-2 by cdc2. Oncogene. 2003 Jul 17;22(29):4524-30. doi: 10.1038/sj.onc.1206767.
12 The expression of retinoblastoma and Sp1 is increased by low concentrations of cyclin-dependent kinase inhibitors. Eur J Biochem. 2003 Dec;270(24):4809-22. doi: 10.1046/j.1432-1033.2003.03874.x.
13 Proliferative suppression by CDK4/6 inhibition: complex function of the retinoblastoma pathway in liver tissue and hepatoma cells. Gastroenterology. 2010 May;138(5):1920-30. doi: 10.1053/j.gastro.2010.01.007. Epub 2010 Jan 25.