U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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
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
Inhibition of cyclin-dependent kinase 1 by purines and pyrrolo[2,3-d]pyrimidines does not correlate with antiviral activity.
2002 Aug
TBP-associated factor 1 overexpression induces tolerance to Doxorubicin in confluent H9c2 cells by an increase in cdk2 activity and cyclin E expression.
2004 Apr
Programmed cell death protein 4 suppresses CDK1/cdc2 via induction of p21(Waf1/Cip1).
2004 Dec
Potent, selective and cell-mediated inhibition of human herpesvirus 6 at an early stage of viral replication by the non-nucleoside compound CMV423.
2004 Jan 15
Recent progress in the discovery and development of cyclin-dependent kinase inhibitors.
2005 Apr
Antiproliferative activity of olomoucine II, a novel 2,6,9-trisubstituted purine cyclin-dependent kinase inhibitor.
2005 Aug
p25/Cdk5-mediated retinoblastoma phosphorylation is an early event in neuronal cell death.
2005 Mar 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 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
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
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
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
Role of senescence and mitotic catastrophe in cancer therapy.
2010 Jan 21
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
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 Dec 16 17:27:26 GMT 2023
Edited
by admin
on Sat Dec 16 17:27:26 GMT 2023
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
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 Sat Dec 16 17:27:28 GMT 2023 , Edited by admin on Sat Dec 16 17:27:28 GMT 2023
NCI_THESAURUS C129825
Created by admin on Sat Dec 16 17:27:28 GMT 2023 , Edited by admin on Sat Dec 16 17:27:28 GMT 2023
Code System Code Type Description
INN
8546
Created by admin on Sat Dec 16 17:27:28 GMT 2023 , Edited by admin on Sat Dec 16 17:27:28 GMT 2023
PRIMARY
EPA CompTox
DTXSID20171928
Created by admin on Sat Dec 16 17:27:28 GMT 2023 , Edited by admin on Sat Dec 16 17:27:28 GMT 2023
PRIMARY
EVMPD
SUB185009
Created by admin on Sat Dec 16 17:27:28 GMT 2023 , Edited by admin on Sat Dec 16 17:27:28 GMT 2023
PRIMARY
NCI_THESAURUS
C62783
Created by admin on Sat Dec 16 17:27:28 GMT 2023 , Edited by admin on Sat Dec 16 17:27:28 GMT 2023
PRIMARY
MERCK INDEX
m9849
Created by admin on Sat Dec 16 17:27:28 GMT 2023 , Edited by admin on Sat Dec 16 17:27:28 GMT 2023
PRIMARY Merck Index
CAS
186692-46-6
Created by admin on Sat Dec 16 17:27:28 GMT 2023 , Edited by admin on Sat Dec 16 17:27:28 GMT 2023
PRIMARY
PUBCHEM
160355
Created by admin on Sat Dec 16 17:27:28 GMT 2023 , Edited by admin on Sat Dec 16 17:27:28 GMT 2023
PRIMARY
ChEMBL
CHEMBL14762
Created by admin on Sat Dec 16 17:27:28 GMT 2023 , Edited by admin on Sat Dec 16 17:27:28 GMT 2023
PRIMARY
FDA UNII
0ES1C2KQ94
Created by admin on Sat Dec 16 17:27:28 GMT 2023 , Edited by admin on Sat Dec 16 17:27:28 GMT 2023
PRIMARY
CHEBI
45307
Created by admin on Sat Dec 16 17:27:28 GMT 2023 , Edited by admin on Sat Dec 16 17:27:28 GMT 2023
PRIMARY
WIKIPEDIA
SELICICLIB
Created by admin on Sat Dec 16 17:27:28 GMT 2023 , Edited by admin on Sat Dec 16 17:27:28 GMT 2023
PRIMARY
SMS_ID
100000170830
Created by admin on Sat Dec 16 17:27:28 GMT 2023 , Edited by admin on Sat Dec 16 17:27:28 GMT 2023
PRIMARY
NSC
701554
Created by admin on Sat Dec 16 17:27:28 GMT 2023 , Edited by admin on Sat Dec 16 17:27:28 GMT 2023
PRIMARY
DRUG BANK
DB06195
Created by admin on Sat Dec 16 17:27:28 GMT 2023 , Edited by admin on Sat Dec 16 17:27:28 GMT 2023
PRIMARY
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