This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.

Identification

Name
Seliciclib
Accession Number
DB06195
Type
Small Molecule
Groups
Investigational
Description

R-roscovitine (Seliciclib or CYC202) is a trial drug in the family of pharmacological cyclin-dependent kinase (CDK) inhibitors that preferentially inhibit multiple enzyme targets including CDK2, CDK7 and CDK9, which alter the growth phase or state within the cell cycle of treated cells. Seliciclib is being developed by Cyclacel. Seliciclib is being researched for the treatment of non-small cell lung cancer (NSCLC), leukemia, HIV infection, herpes simplex infection, and the mechanisms of chronic inflammation disorders.

Structure
Thumb
Synonyms
  • CYC202
  • R-roscovitine
External IDs
AL-39256 / CYC-202 / NSC-701554
Categories
UNII
0ES1C2KQ94
CAS number
186692-46-6
Weight
Average: 354.4493
Monoisotopic: 354.216809484
Chemical Formula
C19H26N6O
InChI Key
BTIHMVBBUGXLCJ-OAHLLOKOSA-N
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
IUPAC Name
(2R)-2-{[6-(benzylamino)-9-(propan-2-yl)-9H-purin-2-yl]amino}butan-1-ol
SMILES
CC[[email protected]](CO)NC1=NC(NCC2=CC=CC=C2)=C2N=CN(C(C)C)C2=N1

Pharmacology

Indication

Investigated for use/treatment in breast cancer, lung cancer, lymphoma (unspecified), multiple myeloma, leukemia (lymphoid), and cancer/tumors (unspecified).

Structured Indications
Not Available
Pharmacodynamics
Not Available
Mechanism of action
TargetActionsOrganism
UCyclin-dependent kinase 1Not AvailableHuman
UCyclin-dependent kinase 2Not AvailableHuman
UMitogen-activated protein kinase 3Not AvailableHuman
UMitogen-activated protein kinase 1Not AvailableHuman
UCyclin-dependent kinase 7Not AvailableHuman
UCyclin-dependent kinase 9Not AvailableHuman
UCasein kinase I isoform epsilonNot AvailableHuman
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Seliciclib.Approved
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Seliciclib.Experimental
AncestimThe risk or severity of cytotoxicity can be increased when Ancestim is combined with Seliciclib.Approved, Investigational, Withdrawn
BevacizumabBevacizumab may increase the cardiotoxic activities of Seliciclib.Approved, Investigational
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Seliciclib.Approved, Investigational
CymarinCymarin may decrease the cardiotoxic activities of Seliciclib.Experimental
DeslanosideDeslanoside may decrease the cardiotoxic activities of Seliciclib.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Seliciclib.Approved, Investigational
DigoxinDigoxin may decrease the cardiotoxic activities of Seliciclib.Approved
Digoxin Immune Fab (Ovine)Digoxin Immune Fab (Ovine) may decrease the cardiotoxic activities of Seliciclib.Approved
GitoformateGitoformate may decrease the cardiotoxic activities of Seliciclib.Experimental
Lanatoside CLanatoside C may decrease the cardiotoxic activities of Seliciclib.Experimental
MetildigoxinMetildigoxin may decrease the cardiotoxic activities of Seliciclib.Experimental
OleandrinOleandrin may decrease the cardiotoxic activities of Seliciclib.Experimental, Investigational
OuabainOuabain may decrease the cardiotoxic activities of Seliciclib.Approved
PeruvosidePeruvoside may decrease the cardiotoxic activities of Seliciclib.Experimental
ProscillaridinProscillaridin may decrease the cardiotoxic activities of Seliciclib.Experimental
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Seliciclib.Approved, Investigational
Food Interactions
Not Available

References

General References
Not Available
External Links
PubChem Compound
160355
ChemSpider
140922
BindingDB
7533
ChEBI
45307
ChEMBL
CHEMBL14762
HET
RRC
Wikipedia
Seliciclib
PDB Entries
1unl / 1ygk / 2a4l / 3ddq

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1RecruitingTreatmentAdvanced Solid Tumors1
1WithdrawnTreatmentCancer, Breast1
2CompletedTreatmentOcular Hypertension / Open-angle Glaucoma (OAG)1
2RecruitingTreatmentCushings Disease1
2RecruitingTreatmentCystic Fibrosis (CF)1
2TerminatedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.163 mg/mLALOGPS
logP3.11ALOGPS
logP2.89ChemAxon
logS-3.3ALOGPS
pKa (Strongest Acidic)14.34ChemAxon
pKa (Strongest Basic)5.55ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area87.89 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity106.14 m3·mol-1ChemAxon
Polarizability40.43 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier-0.5569
Caco-2 permeable-0.5933
P-glycoprotein substrateSubstrate0.8191
P-glycoprotein inhibitor INon-inhibitor0.7527
P-glycoprotein inhibitor IINon-inhibitor0.8302
Renal organic cation transporterNon-inhibitor0.7794
CYP450 2C9 substrateNon-substrate0.8193
CYP450 2D6 substrateNon-substrate0.788
CYP450 3A4 substrateNon-substrate0.5703
CYP450 1A2 substrateInhibitor0.9106
CYP450 2C9 inhibitorInhibitor0.8948
CYP450 2D6 inhibitorInhibitor0.8932
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorInhibitor0.5687
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8394
Ames testNon AMES toxic0.6143
CarcinogenicityNon-carcinogens0.8402
BiodegradationNot ready biodegradable0.9862
Rat acute toxicity2.6040 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8367
hERG inhibition (predictor II)Non-inhibitor0.55
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as 6-alkylaminopurines. These are compounds that contain an alkylamine group attached at the 6-position of a purine. Purine is a bicyclic aromatic compound made up of a pyrimidine ring fused to an imidazole ring.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Imidazopyrimidines
Sub Class
Purines and purine derivatives
Direct Parent
6-alkylaminopurines
Alternative Parents
Benzylamines / Secondary alkylarylamines / Aminopyrimidines and derivatives / N-substituted imidazoles / Imidolactams / Heteroaromatic compounds / Azacyclic compounds / Primary alcohols / Organopnictogen compounds / Hydrocarbon derivatives
Substituents
6-alkylaminopurine / Benzylamine / Aminopyrimidine / Secondary aliphatic/aromatic amine / Monocyclic benzene moiety / N-substituted imidazole / Pyrimidine / Benzenoid / Imidolactam / Imidazole
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
2,6-diaminopurine (CHEBI:45307)

Targets

Details
1. Cyclin-dependent kinase 1
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Rna polymerase ii carboxy-terminal domain kinase activity
Specific Function
Plays a key role in the control of the eukaryotic cell cycle by modulating the centrosome cycle as well as mitotic onset; promotes G2-M transition, and regulates G1 progress and G1-S transition via...
Gene Name
CDK1
Uniprot ID
P06493
Uniprot Name
Cyclin-dependent kinase 1
Molecular Weight
34095.14 Da
References
  1. Iurisci I, Filipski E, Reinhardt J, Bach S, Gianella-Borradori A, Iacobelli S, Meijer L, Levi F: Improved tumor control through circadian clock induction by Seliciclib, a cyclin-dependent kinase inhibitor. Cancer Res. 2006 Nov 15;66(22):10720-8. [PubMed:17108108]
Details
2. Cyclin-dependent kinase 2
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Metal ion binding
Specific Function
Serine/threonine-protein kinase involved in the control of the cell cycle; essential for meiosis, but dispensable for mitosis. Phosphorylates CTNNB1, USP37, p53/TP53, NPM1, CDK7, RB1, BRCA2, MYC, N...
Gene Name
CDK2
Uniprot ID
P24941
Uniprot Name
Cyclin-dependent kinase 2
Molecular Weight
33929.215 Da
References
  1. Iurisci I, Filipski E, Reinhardt J, Bach S, Gianella-Borradori A, Iacobelli S, Meijer L, Levi F: Improved tumor control through circadian clock induction by Seliciclib, a cyclin-dependent kinase inhibitor. Cancer Res. 2006 Nov 15;66(22):10720-8. [PubMed:17108108]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Phosphatase binding
Specific Function
Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK ca...
Gene Name
MAPK3
Uniprot ID
P27361
Uniprot Name
Mitogen-activated protein kinase 3
Molecular Weight
43135.16 Da
References
  1. Iurisci I, Filipski E, Reinhardt J, Bach S, Gianella-Borradori A, Iacobelli S, Meijer L, Levi F: Improved tumor control through circadian clock induction by Seliciclib, a cyclin-dependent kinase inhibitor. Cancer Res. 2006 Nov 15;66(22):10720-8. [PubMed:17108108]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Rna polymerase ii carboxy-terminal domain kinase activity
Specific Function
Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK ca...
Gene Name
MAPK1
Uniprot ID
P28482
Uniprot Name
Mitogen-activated protein kinase 1
Molecular Weight
41389.265 Da
References
  1. Iurisci I, Filipski E, Reinhardt J, Bach S, Gianella-Borradori A, Iacobelli S, Meijer L, Levi F: Improved tumor control through circadian clock induction by Seliciclib, a cyclin-dependent kinase inhibitor. Cancer Res. 2006 Nov 15;66(22):10720-8. [PubMed:17108108]
Details
5. Cyclin-dependent kinase 7
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Transcription coactivator activity
Specific Function
Serine/threonine kinase involved in cell cycle control and in RNA polymerase II-mediated RNA transcription. Cyclin-dependent kinases (CDKs) are activated by the binding to a cyclin and mediate the ...
Gene Name
CDK7
Uniprot ID
P50613
Uniprot Name
Cyclin-dependent kinase 7
Molecular Weight
39038.005 Da
References
  1. Iurisci I, Filipski E, Reinhardt J, Bach S, Gianella-Borradori A, Iacobelli S, Meijer L, Levi F: Improved tumor control through circadian clock induction by Seliciclib, a cyclin-dependent kinase inhibitor. Cancer Res. 2006 Nov 15;66(22):10720-8. [PubMed:17108108]
Details
6. Cyclin-dependent kinase 9
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Transcription regulatory region dna binding
Specific Function
Protein kinase involved in the regulation of transcription. Member of the cyclin-dependent kinase pair (CDK9/cyclin-T) complex, also called positive transcription elongation factor b (P-TEFb), whic...
Gene Name
CDK9
Uniprot ID
P50750
Uniprot Name
Cyclin-dependent kinase 9
Molecular Weight
42777.155 Da
References
  1. Iurisci I, Filipski E, Reinhardt J, Bach S, Gianella-Borradori A, Iacobelli S, Meijer L, Levi F: Improved tumor control through circadian clock induction by Seliciclib, a cyclin-dependent kinase inhibitor. Cancer Res. 2006 Nov 15;66(22):10720-8. [PubMed:17108108]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Protein serine/threonine kinase activity
Specific Function
Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. Can phosphorylate a large number of proteins. Participates in Wnt signal...
Gene Name
CSNK1E
Uniprot ID
P49674
Uniprot Name
Casein kinase I isoform epsilon
Molecular Weight
47314.665 Da
References
  1. Iurisci I, Filipski E, Reinhardt J, Bach S, Gianella-Borradori A, Iacobelli S, Meijer L, Levi F: Improved tumor control through circadian clock induction by Seliciclib, a cyclin-dependent kinase inhibitor. Cancer Res. 2006 Nov 15;66(22):10720-8. [PubMed:17108108]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Prostaglandin-endoperoxide synthase activity
Specific Function
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Constitutively expressed in some tissues in physiological conditions, such as the endothelium, kidney and...
Gene Name
PTGS2
Uniprot ID
P35354
Uniprot Name
Prostaglandin G/H synthase 2
Molecular Weight
68995.625 Da
References
  1. Dey A, Wong ET, Cheok CF, Tergaonkar V, Lane DP: R-Roscovitine simultaneously targets both the p53 and NF-kappaB pathways and causes potentiation of apoptosis: implications in cancer therapy. Cell Death Differ. 2008 Feb;15(2):263-73. Epub 2007 Nov 2. [PubMed:17975552]

Drug created on March 19, 2008 10:16 / Updated on January 05, 2018 16:02