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Details

Stereochemistry ABSOLUTE
Molecular Formula C19H26N6O
Molecular Weight 354.4501
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of SELICICLIB

SMILES

CC[C@]([H])(CO)N=c1[nH]c(c2c(n1)n(cn2)C(C)C)NCc3ccccc3

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 354.4501
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
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: Page: p.3246, 3247
unhealthy, ADULT
n = 6
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 6
Sources: Page: p.3246, 3247
DLT: Asthenia, Hypokalaemia...
Dose limiting toxicities:
Asthenia (33.3%)
Hypokalaemia (33.3%)
Sources: Page: p.3246, 3247
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: Page: p.3245, 3246
unhealthy, ADULT
n = 3
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 3
Sources: Page: p.3245, 3246
Sources: Page: p.3245, 3246
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: Page: p.3246, 3247
unhealthy, ADULT
n = 3
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 3
Sources: Page: p.3246, 3247
Sources: Page: p.3246, 3247
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: Page: p.3245, 3246
unhealthy, ADULT
n = 6
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 6
Sources: Page: p.3245, 3246
DLT: Hypokalaemia, Asthenia...
Dose limiting toxicities:
Hypokalaemia (33.3%)
Asthenia (33.3%)
Vomiting (33.3%)
Nausea (33.3%)
Sources: Page: p.3245, 3246
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: Page: p.32
unhealthy, ADULT
n = 12
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 12
Sources: Page: p.32
DLT: Hyperglycaemia, Fatigue...
Dose limiting toxicities:
Hyperglycaemia (8.3%)
Fatigue (grade 3, 8.3%)
Hyponatraemia (grade 3, 8.3%)
Hypokalaemia (grade 4, 8.3%)
Skin rash (grade 3, 8.3%)
Glycosuria (8.3%)
GGT increased (25%)
Sources: Page: p.32
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: Page: p.3246, 3247
unhealthy, ADULT
n = 6
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 6
Sources: Page: p.3246, 3247
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: Page: p.3246, 3247
unhealthy, ADULT
n = 6
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 6
Sources: Page: p.3246, 3247
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: Page: p.3245, 3246
unhealthy, ADULT
n = 6
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 6
Sources: Page: p.3245, 3246
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: Page: p.3245, 3246
unhealthy, ADULT
n = 6
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 6
Sources: Page: p.3245, 3246
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: Page: p.3245, 3246
unhealthy, ADULT
n = 6
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 6
Sources: Page: p.3245, 3246
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: Page: p.3245, 3246
unhealthy, ADULT
n = 6
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 6
Sources: Page: p.3245, 3246
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: Page: p.32
unhealthy, ADULT
n = 12
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 12
Sources: Page: p.32
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: Page: p.32
unhealthy, ADULT
n = 12
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 12
Sources: Page: p.32
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: Page: p.32
unhealthy, ADULT
n = 12
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 12
Sources: Page: p.32
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: Page: p.32
unhealthy, ADULT
n = 12
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 12
Sources: Page: p.32
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: Page: p.32
unhealthy, ADULT
n = 12
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 12
Sources: Page: p.32
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: Page: p.32
unhealthy, ADULT
n = 12
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 12
Sources: Page: p.32
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: Page: p.32
unhealthy, ADULT
n = 12
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 12
Sources: Page: p.32
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Indirubin-3'-monoxime, a derivative of a Chinese antileukemia medicine, inhibits P-TEFb function and HIV-1 replication.
2005 Dec 2
Potentiation of the lethality of the histone deacetylase inhibitor LAQ824 by the cyclin-dependent kinase inhibitor roscovitine in human leukemia cells.
2005 Nov
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
A phase I trial of the selective oral cyclin-dependent kinase inhibitor seliciclib (CYC202; R-Roscovitine), administered twice daily for 7 days every 21 days.
2007 Jan 15
Seliciclib (CYC202; r-roscovitine) in combination with cytotoxic agents in human uterine sarcoma cell lines.
2007 Jan-Feb
Inhibition of HIV-1 replication by P-TEFb inhibitors DRB, seliciclib and flavopiridol correlates with release of free P-TEFb from the large, inactive form of the complex.
2007 Jul 11
Gateways to clinical trials.
2007 Jul-Aug
Gateways to clinical trials.
2007 Jun
'Seed' analysis of off-target siRNAs reveals an essential role of Mcl-1 in resistance to the small-molecule Bcl-2/Bcl-XL inhibitor ABT-737.
2007 Jun 7
AKT and CDK5/p35 mediate brain-derived neurotrophic factor induction of DARPP-32 in medium size spiny neurons in vitro.
2007 Mar 9
The effects of the CDK inhibitor seliciclib alone or in combination with cisplatin in human uterine sarcoma cell lines.
2007 May
Mitotic arrest-associated apoptosis induced by sodium arsenite in A375 melanoma cells is BUBR1-dependent.
2008 Aug 15
Human cytomegalovirus IE1 protein enhances herpes simplex virus type 1-induced syncytial formation in U373MG cells.
2008 Dec
Small-molecule Bcl-2 antagonists as targeted therapy in oncology.
2008 Dec
You never know: Cdk inhibitors as anti-cancer drugs.
2008 Dec 15
Polycystic kidney diseases: from molecular discoveries to targeted therapeutic strategies.
2008 Feb
Synergistic inhibition of ErbB signaling by combined treatment with seliciclib and ErbB-targeting agents.
2008 Jul 1
Metabolism of the trisubstituted purine cyclin-dependent kinase inhibitor seliciclib (R-roscovitine) in vitro and in vivo.
2008 Mar
The separation of antagonist from agonist effects of trisubstituted purines on CaV2.2 (N-type) channels.
2008 May
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
Role of caspases, calpain and cdk5 in ammonia-induced cell death in developing brain cells.
2008 Nov
Molecular therapies for systemic lupus erythematosus: clinical trials and future prospects.
2009
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
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
Delayed treatment with systemic (S)-roscovitine provides neuroprotection and inhibits in vivo CDK5 activity increase in animal stroke models.
2010 Aug 12
R-Roscovitine (Seliciclib) prevents DNA damage-induced cyclin A1 upregulation and hinders non-homologous end-joining (NHEJ) DNA repair.
2010 Aug 4
Phase I evaluation of seliciclib (R-roscovitine), a novel oral cyclin-dependent kinase inhibitor, in patients with advanced malignancies.
2010 Dec
Role of senescence and mitotic catastrophe in cancer therapy.
2010 Jan 21
Caffeine prevents transcription inhibition and P-TEFb/7SK dissociation following UV-induced DNA damage.
2010 Jun 21
Probing the probes: fitness factors for small molecule tools.
2010 Jun 25
Inhibition of human immunodeficiency virus type-1 by cdk inhibitors.
2010 Mar 24
Graphic rule for drug metabolism systems.
2010 May
Proliferative suppression by CDK4/6 inhibition: complex function of the retinoblastoma pathway in liver tissue and hepatoma cells.
2010 May
Application of new drugs in chronic lymphocytic leukemia.
2010 May 10
ATP-binding cassette B1 transports seliciclib (R-roscovitine), a cyclin-dependent kinase inhibitor.
2010 Nov
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
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 Sat Jun 26 15:23:55 UTC 2021
Edited
by admin
on Sat Jun 26 15:23:55 UTC 2021
Record UNII
0ES1C2KQ94
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
SELICICLIB
INN   MI   WHO-DD  
INN  
Official Name English
AL-39256
Code English
SELICICLIB [MI]
Common Name English
R-ROSCOVITINE
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
SELICICLIB [WHO-DD]
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 Sat Jun 26 15:23:56 UTC 2021 , Edited by admin on Sat Jun 26 15:23:56 UTC 2021
NCI_THESAURUS C129825
Created by admin on Sat Jun 26 15:23:56 UTC 2021 , Edited by admin on Sat Jun 26 15:23:56 UTC 2021
Code System Code Type Description
INN
8546
Created by admin on Sat Jun 26 15:23:56 UTC 2021 , Edited by admin on Sat Jun 26 15:23:56 UTC 2021
PRIMARY
EPA CompTox
186692-46-6
Created by admin on Sat Jun 26 15:23:56 UTC 2021 , Edited by admin on Sat Jun 26 15:23:56 UTC 2021
PRIMARY
EVMPD
SUB185009
Created by admin on Sat Jun 26 15:23:56 UTC 2021 , Edited by admin on Sat Jun 26 15:23:56 UTC 2021
PRIMARY
NCI_THESAURUS
C62783
Created by admin on Sat Jun 26 15:23:56 UTC 2021 , Edited by admin on Sat Jun 26 15:23:56 UTC 2021
PRIMARY
MERCK INDEX
M9849
Created by admin on Sat Jun 26 15:23:56 UTC 2021 , Edited by admin on Sat Jun 26 15:23:56 UTC 2021
PRIMARY Merck Index
CAS
186692-46-6
Created by admin on Sat Jun 26 15:23:56 UTC 2021 , Edited by admin on Sat Jun 26 15:23:56 UTC 2021
PRIMARY
PUBCHEM
160355
Created by admin on Sat Jun 26 15:23:56 UTC 2021 , Edited by admin on Sat Jun 26 15:23:56 UTC 2021
PRIMARY
ChEMBL
CHEMBL14762
Created by admin on Sat Jun 26 15:23:56 UTC 2021 , Edited by admin on Sat Jun 26 15:23:56 UTC 2021
PRIMARY
FDA UNII
0ES1C2KQ94
Created by admin on Sat Jun 26 15:23:56 UTC 2021 , Edited by admin on Sat Jun 26 15:23:56 UTC 2021
PRIMARY
WIKIPEDIA
SELICICLIB
Created by admin on Sat Jun 26 15:23:56 UTC 2021 , Edited by admin on Sat Jun 26 15:23:56 UTC 2021
PRIMARY
DRUG BANK
DB06195
Created by admin on Sat Jun 26 15:23:56 UTC 2021 , Edited by admin on Sat Jun 26 15:23:56 UTC 2021
PRIMARY
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