OLOMOUCINE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C15H18N6O
Molecular Weight	298.343
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN1C=NC2=C1N=C(NCCO)N=C2NCC3=CC=CC=C3

InChI

InChIKey=GTVPOLSIJWJJNY-UHFFFAOYSA-N

InChI=1S/C15H18N6O/c1-21-10-18-12-13(17-9-11-5-3-2-4-6-11)19-15(16-7-8-22)20-14(12)21/h2-6,10,22H,7-9H2,1H3,(H2,16,17,19,20)

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/8626506 | https://www.ncbi.nlm.nih.gov/pubmed/7549905 | https://www.scbt.com/scbt/product/olomoucine-101622-51-9 | https://www.ncbi.nlm.nih.gov/pubmed/16000586 |

Olomoucine acts as a competitive inhibitor of ATP in cyclin-dependent kinase 1/2/5, and mitogen-activated protein kinase 1. Olomoucine is an anti-mitotic compound that induces cell death preferentially in cancer cell lines, but also at a slower rate in non-cancer cells. It has been studied pre-clinically in a number of cancer models but has not been reported in any human trials. Olomoucine has also seen some preliminary investigation in mouse models of Herpes Simplex Viral Encephalitis.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Cyclin-dependent kinase 2 22 Target ID: P24941 Gene ID: 1017.0 Gene Symbol: CDK2 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/7549905 \| https://www.ncbi.nlm.nih.gov/pubmed/7479711 \| https://www.ncbi.nlm.nih.gov/pubmed/7925396	Inhibitor 8297	7.0 µM [IC50]
Cyclin-dependent-like kinase 5 1 Target ID: Q00535 Gene ID: 1020.0 Gene Symbol: CDK5 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/7925396	Inhibitor 8297	3.0 µM [IC50]
Mitogen-activated protein kinase 1 3 Target ID: P28482 Gene ID: 5594.0 Gene Symbol: MAPK1 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/7925396	Inhibitor 8297	25.0 µM [IC50]
Cyclin-dependent kinase 1 27 Target ID: P06493 Gene ID: 983.0 Gene Symbol: CDK1 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/8626506	Inhibitor 8297	7.0 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Cancer 592 Sources: http://adis.springer.com/drugs/800008577 https://www.ncbi.nlm.nih.gov/pubmed/16000586 https://www.ncbi.nlm.nih.gov/pubmed/10602500 https://www.ncbi.nlm.nih.gov/pubmed/17094472	Primary		Preclinical	Unknown Approved Use Unknown
Herpes virus encephalitis 2 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27241721	Primary		Preclinical	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
In vitro glycosidation potential towards olomoucine-type cyclin-dependent kinase inhibitors in rodent and primate microsomes.	2003	12899660
Mixed ligand complexes of platinum(II) and palladium(II) with cytokinin-derived compounds Bohemine and Olomoucine: X-ray structure of [Pt(BohH+-N7)Cl(3)].9/5H2O [Boh=6-(benzylamino)-2-[(3-(hydroxypropyl)-amino]-9-isopropylpurine, Bohemine].	2003 Apr 1	12667701
Involvement of the transcription factor E2F1/Rb in kainic acid-induced death of murine cerebellar granule cells.	2003 Aug 19	12941462
Changes in the activities of hydroxysteroid dehydrogenases in mouse oocytes during meiotic maturation.	2003 Dec	14967895
The expression of retinoblastoma and Sp1 is increased by low concentrations of cyclin-dependent kinase inhibitors.	2003 Dec	14653808
An inhibition of cyclin-dependent kinases that lengthens, but does not arrest, neuroepithelial cell cycle induces premature neurogenesis.	2003 Dec 15	14625388
Roscovitine and other purines as kinase inhibitors. From starfish oocytes to clinical trials.	2003 Jun	12809528
Cdk2 activity is associated with depolarization of mitochondrial membrane potential during apoptosis.	2003 Jun 13	12767926
Growth cones contain a dynamic population of neurofilament subunits.	2003 Mar	12589678
Synthesis and biological evaluations of pyrazolo[3,4-d]pyrimidines as cyclin-dependent kinase 2 inhibitors.	2003 May	12767603
Cdk5/p35 and Rho-kinase mediate ephrin-A5-induced signaling in retinal ganglion cells.	2003 Nov	14664814
Prevention of dopaminergic neuronal death by cyclic AMP in mixed neuronal/glial mesencephalic cultures requires the repression of presumptive astrocytes.	2003 Sep	12920193
Synergic effects of the cyclin-dependent kinase (CDK) inhibitor olomoucine and androgen-antagonist bicalutamide on prostatic cancer cell lines.	2004	15640940
Expression profiles of a human pancreatic cancer cell line upon induction of apoptosis search for modulators in cancer therapy.	2004	15557790
Cell differentiation, caspase inhibition, and macromolecular synthesis blockage, but not BCL-2 or BCL-XL proteins, protect SH-SY5Y cells from apoptosis triggered by two CDK inhibitory drugs.	2004 Apr 15	15051486
Cdk5 regulates activation and localization of Src during corneal epithelial wound closure.	2004 Aug 15	15280426
Protection of renal cells from cisplatin toxicity by cell cycle inhibitors.	2004 Feb	12965891
Angiostatin-induced inhibition of endothelial cell proliferation/apoptosis is associated with the down-regulation of cell cycle regulatory protein cdk5.	2004 Feb 1	14743398
Nuclear translocation of the Hsp70/Hsp90 organizing protein mSTI1 is regulated by cell cycle kinases.	2004 Feb 15	14754904
Correlation between semaphorin3A-induced facilitation of axonal transport and local activation of a translation initiation factor eukaryotic translation initiation factor 4E.	2004 Jul 7	15240808
A novel CDK5-dependent pathway for regulating GSK3 activity and kinesin-driven motility in neurons.	2004 Jun 2	15152189
Activation of cyclin-dependent kinase 5 is involved in axonal regeneration.	2004 Mar	15033170
Cassette dosing pharmacokinetics of a library of 2,6,9-trisubstituted purine cyclin-dependent kinase 2 inhibitors prepared by parallel synthesis.	2004 Mar	15026556
Development of an assay to screen for inhibitors of tau phosphorylation by cdk5.	2004 Mar	15006135
Xylocydine, a novel inhibitor of cyclin-dependent kinases, prevents the tumor necrosis factor-related apoptosis-inducing ligand-induced apoptotic cell death of SK-HEP-1 cells.	2004 Mar	14617691
Roscovitine, olomoucine, purvalanol: inducers of apoptosis in maturing cerebellar granule neurons.	2004 May 15	15130771
N-glucosylation of cytokinins by glycosyltransferases of Arabidopsis thaliana.	2004 Nov 12	15342621
Cyclin-dependent kinase inhibitors attenuate protein hyperphosphorylation, cytoskeletal lesion formation, and motor defects in Niemann-Pick Type C mice.	2004 Sep	15331409
Mitogen-activated protein kinase regulates neurofilament axonal transport.	2004 Sep 15	15331628
Phosphorylation of Sp1 by cyclin-dependent kinase 2 modulates the role of Sp1 in CTP:phosphocholine cytidylyltransferase alpha regulation during the S phase of the cell cycle.	2004 Sep 17	15247247
Cell cycle arrest induced in human breast cancer cells by cyclin-dependent kinase inhibitors: a comparison of the effects exerted by roscovitine and olomoucine.	2004 Sep-Oct	15591654
Phosphorylated amyloid-beta: the toxic intermediate in alzheimer's disease neurodegeneration.	2005	15709490
Resveratrol-induced apoptotic death in human U251 glioma cells.	2005 Apr	15827328
Antiproliferative activity of olomoucine II, a novel 2,6,9-trisubstituted purine cyclin-dependent kinase inhibitor.	2005 Aug	16003486
Molecular models of protein kinase 6 from Plasmodium falciparum.	2005 Dec	16096806
Activation of CYP1A1 gene expression during primary culture of mouse hepatocytes.	2005 Dec 15	16169145
Cdk inhibition in human cells compromises chk1 function and activates a DNA damage response.	2005 Feb 1	15705874
Clinical anticancer drug development: targeting the cyclin-dependent kinases.	2005 Jan 17	15558073
CIL-102 interacts with microtubule polymerization and causes mitotic arrest following apoptosis in the human prostate cancer PC-3 cell line.	2005 Jan 28	15536083
In vitro and in vivo pharmacokinetic-pharmacodynamic relationships for the trisubstituted aminopurine cyclin-dependent kinase inhibitors olomoucine, bohemine and CYC202.	2005 Jul 1	16000586
Signaling pathways in ascidian oocyte maturation: effects of various inhibitors and activators on germinal vesicle breakdown.	2005 May	15921501
Cdk2 activity is dispensable for triggering replicon initiation after transient hypoxia in T24 cells.	2005 Nov	16262700
Caspase 8/10 are not mediating apoptosis in neuroblastoma cells treated with CDK inhibitory drugs.	2005 Nov 7	16243312
Cdk5-dependent regulation of glucose-stimulated insulin secretion.	2005 Oct	16155576
During male pronuclei formation chromatin remodeling is uncoupled from nucleus decondensation.	2005 Oct 1	16088960
DNA damage induces cdk2 protein levels and histone H2B phosphorylation in SH-SY5Y neuroblastoma cells.	2005 Sep	16155345
Role of the cell cycle in the pathobiology of central nervous system trauma.	2005 Sep	16082214
Slowed N-type calcium channel (CaV2.2) deactivation by the cyclin-dependent kinase inhibitor roscovitine.	2005 Sep	15951378
Zinc(II) complexes with potent cyclin-dependent kinase inhibitors derived from 6-benzylaminopurine: synthesis, characterization, X-ray structures and biological activity.	2006 Feb	16386795
The role of protein kinase A and cyclin-dependent (CDC2) kinase in the control of basal and IGF-II-induced proliferation and secretory activity of chicken ovarian cells.	2006 Mar	16029936

Patents

Sample Use Guides

In Vivo Use Guide

Pharmacokinetic properties were characterized in mice which were administered with 50 mg/kg of oral olomoucine.

Route of Administration: Oral

In Vitro Use Guide

Human MCF-7 and IMR-90 cell lines were grown in Dulbecco's modified Eagle's medium, and cell cycles were arrested at the G2/M or G0/G1 checkpoints respectively. Cells were released from cycle blocking and olomoucine (150 uM) was added after 4 hours. Treatment induces nuclear accumulation of wt p53 and a delocalization of nucleolin from the nucleolus in all cells regardless of cell cycle stage. This triggers rapid death of human tumor cells and a less rapid death of non-tumor cells.

Name

Type

Language

OLOMOUCINE

Common Name

English

ETHANOL, 2-((9-METHYL-6-((PHENYLMETHYL)AMINO)-9H-PURIN-2-YL)AMINO)-

Systematic Name

English

NSC-666096

Code

English

Code System Code Type Description

EPA CompTox

DTXSID90144068