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Details

Stereochemistry ABSOLUTE
Molecular Formula C19H26N6O
Molecular Weight 354.4493
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of SELICICLIB

SMILES

CC[C@H](CO)NC1=NC2=C(N=CN2C(C)C)C(NCC3=CC=CC=C3)=N1

InChI

InChIKey=BTIHMVBBUGXLCJ-OAHLLOKOSA-N
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

HIDE SMILES / InChI

Molecular Formula C19H26N6O
Molecular Weight 354.4493
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Seliciclib (CYC202, R-roscovitine) is a second-generation orally available cyclin-dependent kinases (CDKs) inhibitor that competes for ATP binding sites on these kinases. It is a direct inhibitor of cyclin CDK2/E, CDK2/A and it has inhibitory effects on cyclin H/CDK7, CDK5, and CDK9. CDKs are enzymes that are central to the process of cell division and cell cycle control and play pivotal roles in cancer cell growth and DNA damage repair. Seliciclib exerts an anti-proliferative effect via several key mechanisms: selective downregulation of proliferative and survival proteins and upregulation of p53, leading to growth arrest or apoptosis. The second one is decreasing phosphorylation of Rb and modulating E2F transcriptional activity leading to growth arrest or apoptosis. Seliciclib is currently in phase II clinical trial as a drug candidate for the treatment of Cushing's disease and as a potential therapeutic agent for the treatment of cystic fibrosis (CF). In addition, it is in Phase II trials for non-small cell lung cancer and nasopharyngeal carcinoma.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
0.1 µM [IC50]
0.81 µM [IC50]
0.36 µM [IC50]
0.2 µM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
3.76 μg/mL
1600 mg single, oral
dose: 1600 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
SELICICLIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
24.73 μg × h/mL
1600 mg single, oral
dose: 1600 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
SELICICLIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
3.11 h
1600 mg single, oral
dose: 1600 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
SELICICLIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
1800 mg 2 times / day multiple, oral
Highest studied dose
Dose: 1800 mg, 2 times / day
Route: oral
Route: multiple
Dose: 1800 mg, 2 times / day
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
DLT: Hypokalaemia, Asthenia...
Dose limiting toxicities:
Hypokalaemia (33.3%)
Asthenia (33.3%)
Sources:
1250 mg 2 times / day multiple, oral
MTD
Dose: 1250 mg, 2 times / day
Route: oral
Route: multiple
Dose: 1250 mg, 2 times / day
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
1600 mg 2 times / day multiple, oral
MTD
Dose: 1600 mg, 2 times / day
Route: oral
Route: multiple
Dose: 1600 mg, 2 times / day
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
1600 mg 2 times / day multiple, oral
Studied dose
Dose: 1600 mg, 2 times / day
Route: oral
Route: multiple
Dose: 1600 mg, 2 times / day
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
DLT: Vomiting, Nausea...
Dose limiting toxicities:
Vomiting (33.3%)
Nausea (33.3%)
Asthenia (33.3%)
Hypokalaemia (33.3%)
Sources:
800 mg 2 times / day multiple, oral
Studied dose
Dose: 800 mg, 2 times / day
Route: oral
Route: multiple
Dose: 800 mg, 2 times / day
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Sources:
DLT: GGT increased, Hyperglycaemia...
Dose limiting toxicities:
GGT increased (25%)
Hyperglycaemia (8.3%)
Glycosuria (8.3%)
Fatigue (grade 3, 8.3%)
Skin rash (grade 3, 8.3%)
Hyponatraemia (grade 3, 8.3%)
Hypokalaemia (grade 4, 8.3%)
Sources:
AEs

AEs

AESignificanceDosePopulation
Asthenia 33.3%
DLT
1800 mg 2 times / day multiple, oral
Highest studied dose
Dose: 1800 mg, 2 times / day
Route: oral
Route: multiple
Dose: 1800 mg, 2 times / day
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
Hypokalaemia 33.3%
DLT
1800 mg 2 times / day multiple, oral
Highest studied dose
Dose: 1800 mg, 2 times / day
Route: oral
Route: multiple
Dose: 1800 mg, 2 times / day
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
Asthenia 33.3%
DLT
1600 mg 2 times / day multiple, oral
Studied dose
Dose: 1600 mg, 2 times / day
Route: oral
Route: multiple
Dose: 1600 mg, 2 times / day
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
Hypokalaemia 33.3%
DLT
1600 mg 2 times / day multiple, oral
Studied dose
Dose: 1600 mg, 2 times / day
Route: oral
Route: multiple
Dose: 1600 mg, 2 times / day
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
Nausea 33.3%
DLT
1600 mg 2 times / day multiple, oral
Studied dose
Dose: 1600 mg, 2 times / day
Route: oral
Route: multiple
Dose: 1600 mg, 2 times / day
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
Vomiting 33.3%
DLT
1600 mg 2 times / day multiple, oral
Studied dose
Dose: 1600 mg, 2 times / day
Route: oral
Route: multiple
Dose: 1600 mg, 2 times / day
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
GGT increased 25%
DLT
800 mg 2 times / day multiple, oral
Studied dose
Dose: 800 mg, 2 times / day
Route: oral
Route: multiple
Dose: 800 mg, 2 times / day
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Sources:
Glycosuria 8.3%
DLT
800 mg 2 times / day multiple, oral
Studied dose
Dose: 800 mg, 2 times / day
Route: oral
Route: multiple
Dose: 800 mg, 2 times / day
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Sources:
Hyperglycaemia 8.3%
DLT
800 mg 2 times / day multiple, oral
Studied dose
Dose: 800 mg, 2 times / day
Route: oral
Route: multiple
Dose: 800 mg, 2 times / day
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Sources:
Fatigue grade 3, 8.3%
DLT
800 mg 2 times / day multiple, oral
Studied dose
Dose: 800 mg, 2 times / day
Route: oral
Route: multiple
Dose: 800 mg, 2 times / day
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Sources:
Hyponatraemia grade 3, 8.3%
DLT
800 mg 2 times / day multiple, oral
Studied dose
Dose: 800 mg, 2 times / day
Route: oral
Route: multiple
Dose: 800 mg, 2 times / day
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Sources:
Skin rash grade 3, 8.3%
DLT
800 mg 2 times / day multiple, oral
Studied dose
Dose: 800 mg, 2 times / day
Route: oral
Route: multiple
Dose: 800 mg, 2 times / day
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Sources:
Hypokalaemia grade 4, 8.3%
DLT
800 mg 2 times / day multiple, oral
Studied dose
Dose: 800 mg, 2 times / day
Route: oral
Route: multiple
Dose: 800 mg, 2 times / day
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Sources:
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Programmed cell death protein 4 suppresses CDK1/cdc2 via induction of p21(Waf1/Cip1).
2004 Dec
P21Cip1 is a critical mediator of the cytotoxic action of thymidylate synthase inhibitors in colorectal carcinoma cells.
2004 Sep 1
Antiproliferative activity of olomoucine II, a novel 2,6,9-trisubstituted purine cyclin-dependent kinase inhibitor.
2005 Aug
Seliciclib (CYC202 or R-roscovitine), a small-molecule cyclin-dependent kinase inhibitor, mediates activity via down-regulation of Mcl-1 in multiple myeloma.
2005 Aug 1
Indirubin-3'-monoxime, a derivative of a Chinese antileukemia medicine, inhibits P-TEFb function and HIV-1 replication.
2005 Dec 2
Metabolism and pharmacokinetics of the cyclin-dependent kinase inhibitor R-roscovitine in the mouse.
2005 Jan
Antiviral activity of CYC202 in HIV-1-infected cells.
2005 Jan 28
Seliciclib (CYC202, R-Roscovitine) induces cell death in multiple myeloma cells by inhibition of RNA polymerase II-dependent transcription and down-regulation of Mcl-1.
2005 Jun 15
p25/Cdk5-mediated retinoblastoma phosphorylation is an early event in neuronal cell death.
2005 Mar 15
Improved tumor control through circadian clock induction by Seliciclib, a cyclin-dependent kinase inhibitor.
2006 Nov 15
The cyclin-dependent kinase inhibitor seliciclib (R-roscovitine; CYC202) decreases the expression of mitotic control genes and prevents entry into mitosis.
2007 Dec 15
Cyclin-dependent kinase inhibitor seliciclib shows in vitro activity in diffuse large B-cell lymphomas.
2007 Jan
Seliciclib (CYC202; r-roscovitine) in combination with cytotoxic agents in human uterine sarcoma cell lines.
2007 Jan-Feb
Gateways to clinical trials.
2007 Jul-Aug
Gateways to clinical trials.
2007 Jun
Crosstalk among Bcl-2 family members in B-CLL: seliciclib acts via the Mcl-1/Noxa axis and gradual exhaustion of Bcl-2 protection.
2007 Nov
Antiproliferative effects of sapacitabine (CYC682), a novel 2'-deoxycytidine-derivative, in human cancer cells.
2007 Sep 3
Human cytomegalovirus IE1 protein enhances herpes simplex virus type 1-induced syncytial formation in U373MG cells.
2008 Dec
You never know: Cdk inhibitors as anti-cancer drugs.
2008 Dec 15
Metabolism of the trisubstituted purine cyclin-dependent kinase inhibitor seliciclib (R-roscovitine) in vitro and in vivo.
2008 Mar
Lysine methylation of HIV-1 Tat regulates transcriptional activity of the viral LTR.
2008 May 22
Effect of seliciclib (CYC202, R-roscovitine) on lymphocyte alloreactivity and acute kidney allograft rejection in rat.
2008 May 27
Molecular therapies for systemic lupus erythematosus: clinical trials and future prospects.
2009
Liver circadian clock, a pharmacologic target of cyclin-dependent kinase inhibitor seliciclib.
2009 Aug
The cyclin-dependent kinase inhibitor 5, 6-dichloro-1-beta-D-ribofuranosylbenzimidazole induces nongenotoxic, DNA replication-independent apoptosis of normal and leukemic cells, regardless of their p53 status.
2009 Aug 12
Seliciclib in malignancies.
2009 Dec
Regulation of HIV-1 transcription in cells of the monocyte-macrophage lineage.
2009 Dec 23
Pharmacodynamic effects of seliciclib, an orally administered cell cycle modulator, in undifferentiated nasopharyngeal cancer.
2009 Feb 15
Induction of cytotoxicity, apoptosis and cell cycle arrest by 1-t-butyl carbamoyl, 7-methyl-indole-3-ethyl isothiocyanate (NB7M) in nervous system cancer cells.
2009 Feb 6
Seliciclib (CYC202, R-roscovitine) enhances the antitumor effect of doxorubicin in vivo in a breast cancer xenograft model.
2009 Jan 15
Therapeutic efficacy of seliciclib in combination with ionizing radiation for human nasopharyngeal carcinoma.
2009 Jun 1
Development of cell-cycle inhibitors for cancer therapy.
2009 Mar
Gateways to clinical trials.
2009 Nov
Cdk2 plays a critical role in hepatocyte cell cycle progression and survival in the setting of cyclin D1 expression in vivo.
2009 Sep 1
Phase I evaluation of seliciclib (R-roscovitine), a novel oral cyclin-dependent kinase inhibitor, in patients with advanced malignancies.
2010 Dec
Healthy clocks, healthy body, healthy mind.
2010 Jan
Targeting the cyclin E-Cdk-2 complex represses lung cancer growth by triggering anaphase catastrophe.
2010 Jan 1
Role of senescence and mitotic catastrophe in cancer therapy.
2010 Jan 21
Application of new drugs in chronic lymphocytic leukemia.
2010 May 10
Combination of sapacitabine and HDAC inhibitors stimulates cell death in AML and other tumour types.
2010 Oct 26
Role of NOXA and its ubiquitination in proteasome inhibitor-induced apoptosis in chronic lymphocytic leukemia cells.
2010 Sep
Cyclin-dependent kinase activity controls the onset of the HCMV lytic cycle.
2010 Sep 9
Pyrazolo[4,3-d]pyrimidine bioisostere of roscovitine: evaluation of a novel selective inhibitor of cyclin-dependent kinases with antiproliferative activity.
2011 Apr 28
A bioinformatical and functional approach to identify novel strategies for chemoprevention of colorectal cancer.
2011 Apr 28
Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity.
2011 Oct 30
Use of ATP analogs to inhibit HIV-1 transcription.
2012 Oct 10
A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery.
2013 Apr 15
Comparative structural and functional studies of 4-(thiazol-5-yl)-2-(phenylamino)pyrimidine-5-carbonitrile CDK9 inhibitors suggest the basis for isotype selectivity.
2013 Feb 14
Synergism of cyclin-dependent kinase inhibitors with camptothecin derivatives in small cell lung cancer cell lines.
2014 Feb 17
Aryl hydrocarbon receptor-dependent up-regulation of the heterodimeric amino acid transporter LAT1 (SLC7A5)/CD98hc (SLC3A2) by diesel exhaust particle extract in human bronchial epithelial cells.
2016 Jan 1

Sample Use Guides

Cushing Disease: R-roscovitine 400 mg oral administration twice daily for 4 days every week for total of 4 weeks. cystic fibrosis: 200 or 400 mg roscovitine (8) or placebo (4) once daily for 4 cycles of 7 days (4 days "on" and 3 days "off")
Route of Administration: Oral
CDK2 inhibitors have been proposed as effective anti-cancer therapeutics. It was shown that CYC202 (R-roscovitine) is a potent inhibitor of recombinant CDK2/cyclin E kinase activity (IC(50) = 0.10 microM) with an average cytotoxic IC(50) of 15.2 microM in a panel of 19 human tumour cell lines, and was also demonstrated selectivity for rapidly proliferating cells over non-proliferating cells. A study of the cell cycle effects of CYC202 in Lovo colorectal carcinoma cells showed that the major effect was not the predicted arrest in one part of the cycle, but rather an induction of cell death from all compartments of the cell cycle.
Substance Class Chemical
Created
by admin
on Wed Apr 02 09:07:11 GMT 2025
Edited
by admin
on Wed Apr 02 09:07:11 GMT 2025
Record UNII
0ES1C2KQ94
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
AL-39256
Preferred Name English
SELICICLIB
INN   MI   WHO-DD  
INN  
Official Name English
SELICICLIB [MI]
Common Name English
R-ROSCOVITINE
Common Name English
Seliciclib [WHO-DD]
Common Name English
CYC-202
Code English
(2R)-2-((6-BENZYLAMINO-9-(PROPAN-2-YL)-9H-PURIN-2-YL)AMINO)BUTAN-1-OL
Systematic Name English
seliciclib [INN]
Common Name English
ROSCOVITINE
Common Name English
NSC-701554
Code English
ROSCOVITIN
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C2185
Created by admin on Wed Apr 02 09:07:11 GMT 2025 , Edited by admin on Wed Apr 02 09:07:11 GMT 2025
NCI_THESAURUS C129825
Created by admin on Wed Apr 02 09:07:11 GMT 2025 , Edited by admin on Wed Apr 02 09:07:11 GMT 2025
Code System Code Type Description
INN
8546
Created by admin on Wed Apr 02 09:07:11 GMT 2025 , Edited by admin on Wed Apr 02 09:07:11 GMT 2025
PRIMARY
EPA CompTox
DTXSID20171928
Created by admin on Wed Apr 02 09:07:11 GMT 2025 , Edited by admin on Wed Apr 02 09:07:11 GMT 2025
PRIMARY
EVMPD
SUB185009
Created by admin on Wed Apr 02 09:07:11 GMT 2025 , Edited by admin on Wed Apr 02 09:07:11 GMT 2025
PRIMARY
NCI_THESAURUS
C62783
Created by admin on Wed Apr 02 09:07:11 GMT 2025 , Edited by admin on Wed Apr 02 09:07:11 GMT 2025
PRIMARY
MERCK INDEX
m9849
Created by admin on Wed Apr 02 09:07:11 GMT 2025 , Edited by admin on Wed Apr 02 09:07:11 GMT 2025
PRIMARY Merck Index
CAS
186692-46-6
Created by admin on Wed Apr 02 09:07:11 GMT 2025 , Edited by admin on Wed Apr 02 09:07:11 GMT 2025
PRIMARY
PUBCHEM
160355
Created by admin on Wed Apr 02 09:07:11 GMT 2025 , Edited by admin on Wed Apr 02 09:07:11 GMT 2025
PRIMARY
ChEMBL
CHEMBL14762
Created by admin on Wed Apr 02 09:07:11 GMT 2025 , Edited by admin on Wed Apr 02 09:07:11 GMT 2025
PRIMARY
FDA UNII
0ES1C2KQ94
Created by admin on Wed Apr 02 09:07:11 GMT 2025 , Edited by admin on Wed Apr 02 09:07:11 GMT 2025
PRIMARY
CHEBI
45307
Created by admin on Wed Apr 02 09:07:11 GMT 2025 , Edited by admin on Wed Apr 02 09:07:11 GMT 2025
PRIMARY
WIKIPEDIA
SELICICLIB
Created by admin on Wed Apr 02 09:07:11 GMT 2025 , Edited by admin on Wed Apr 02 09:07:11 GMT 2025
PRIMARY
SMS_ID
100000170830
Created by admin on Wed Apr 02 09:07:11 GMT 2025 , Edited by admin on Wed Apr 02 09:07:11 GMT 2025
PRIMARY
NSC
701554
Created by admin on Wed Apr 02 09:07:11 GMT 2025 , Edited by admin on Wed Apr 02 09:07:11 GMT 2025
PRIMARY
DRUG BANK
DB06195
Created by admin on Wed Apr 02 09:07:11 GMT 2025 , Edited by admin on Wed Apr 02 09:07:11 GMT 2025
PRIMARY
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