olomoucine (CHEBI:44661)

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CHEBI:44661 - olomoucine

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ChEBI Name	olomoucine

ChEBI ID	CHEBI:44661

Definition	A 9H-purine that is substituted by a (2-hydroxyethyl)nitrilo, benzylnitrilo and a methyl group at positions 2,6 and 9, respectively. It is a cyclin-dependent kinase inhibitor.

Stars	This entity has been manually annotated by the ChEBI Team.

Supplier Information	ChemicalBook:CB0309080, eMolecules:592965, ZINC000001641925

Download	Molfile XML SDF

more structures >>

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40 42 0 0 0 0 999 V2000

3.0780 0.0460 2.5660 N 0 0 0 0 0 0 0 0 0 0 0 0

3.8320 0.1170 1.4310 C 0 0 0 0 0 0 0 0 0 0 0 0

3.0600 0.0990 0.3840 N 0 0 0 0 0 0 0 0 0 0 0 0

1.7650 0.0170 0.7790 C 0 0 0 0 0 0 0 0 0 0 0 0

1.7630 -0.0230 2.1830 C 0 0 0 0 0 0 0 0 0 0 0 0

0.5310 -0.0350 0.1090 C 0 0 0 0 0 0 0 0 0 0 0 0

-0.5800 -0.1160 0.8310 N 0 0 0 0 0 0 0 0 0 0 0 0

-0.5370 -0.1460 2.1560 C 0 0 0 0 0 0 0 0 0 0 0 0

0.6020 -0.0990 2.8270 N 0 0 0 0 0 0 0 0 0 0 0 0

3.5820 0.0390 3.9420 C 0 0 0 0 0 0 0 0 0 0 0 0

-1.7250 -0.2310 2.8630 N 0 0 0 0 0 0 0 0 0 0 0 0

-3.0010 -0.2850 2.1460 C 0 0 0 0 0 0 0 0 0 0 0 0

-4.1490 -0.3750 3.1530 C 0 0 0 0 0 0 0 0 0 0 0 0

-4.1280 0.7730 4.0030 O 0 0 0 0 0 0 0 0 0 0 0 0

0.4760 -0.0040 -1.2730 N 0 0 0 0 0 0 0 0 0 0 0 0

-0.8190 -0.0600 -1.9550 C 0 0 0 0 0 0 0 0 0 0 0 0

-0.4370 -1.1840 -4.1590 C 0 0 0 0 0 0 0 0 0 0 0 0

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-0.6030 -0.0110 -3.4460 C 0 0 0 0 0 0 0 0 0 0 0 0

4.9100 0.1780 1.4050 H 0 0 0 0 0 0 0 0 0 0 0 0

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2.9020 -0.5290 4.5750 H 0 0 0 0 0 0 0 0 0 0 0 0

4.5700 -0.4190 3.9650 H 0 0 0 0 0 0 0 0 0 0 0 0

-1.7120 -0.2540 3.8320 H 0 0 0 0 0 0 0 0 0 0 0 0

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-5.0990 -0.4150 2.6190 H 0 0 0 0 0 0 0 0 0 0 0 0

-4.0330 -1.2750 3.7570 H 0 0 0 0 0 0 0 0 0 0 0 0

-4.8660 0.6770 4.6210 H 0 0 0 0 0 0 0 0 0 0 0 0

1.2940 0.0540 -1.7900 H 0 0 0 0 0 0 0 0 0 0 0 0

-1.3280 -0.9870 -1.6920 H 0 0 0 0 0 0 0 0 0 0 0 0

-1.4280 0.7890 -1.6480 H 0 0 0 0 0 0 0 0 0 0 0 0

-0.4620 -2.1350 -3.6480 H 0 0 0 0 0 0 0 0 0 0 0 0

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2 3 4 0 0 0 0

2 23 1 0 0 0 0

3 4 4 0 0 0 0

4 5 4 0 0 0 0

4 6 4 0 0 0 0

5 9 4 0 0 0 0

6 7 4 0 0 0 0

6 15 1 0 0 0 0

7 8 4 0 0 0 0

8 9 4 0 0 0 0

8 11 1 0 0 0 0

10 24 1 0 0 0 0

10 25 1 0 0 0 0

10 26 1 0 0 0 0

11 12 1 0 0 0 0

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12 13 1 0 0 0 0

12 28 1 0 0 0 0

12 29 1 0 0 0 0

13 14 1 0 0 0 0

13 30 1 0 0 0 0

13 31 1 0 0 0 0

14 32 1 0 0 0 0

15 16 1 0 0 0 0

15 33 1 0 0 0 0

16 22 1 0 0 0 0

16 34 1 0 0 0 0

16 35 1 0 0 0 0

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17 22 4 0 0 0 0

17 36 1 0 0 0 0

18 19 4 0 0 0 0

18 37 1 0 0 0 0

19 20 4 0 0 0 0

19 38 1 0 0 0 0

20 21 4 0 0 0 0

20 39 1 0 0 0 0

21 22 4 0 0 0 0

21 40 1 0 0 0 0

M END): 17 ms

reading 40 atoms

ModelSet: haveSymmetry:false haveUnitcells:false haveFractionalCoord:false

1 model in this collection. Use getProperty "modelInfo" or getProperty "auxiliaryInfo" to inspect them.

Default Van der Waals type for model set to Babel

40 atoms created

ModelSet: not autobonding; use forceAutobond=true to force automatic bond creation

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Molfile expand

Formula

C15H18N6O

Net Charge

Average Mass

298.350

Monoisotopic Mass

298.15421

InChI

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)

InChIKey

GTVPOLSIJWJJNY-UHFFFAOYSA-N

SMILES

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

Roles Classification
Chemical Role(s):	Bronsted base A molecular entity capable of accepting a hydron from a donor (Bronsted acid). (via organic amino compound )

Biological Role(s):	EC 2.7.11.22 (cyclin-dependent kinase) inhibitor An EC 2.7.11.* (protein-serine/threonine kinase) inhibitor that interferes with the action of cyclin-dependent kinase (EC 2.7.11.22).

View more via ChEBI Ontology

ChEBI Ontology
Outgoing	olomoucine (CHEBI:44661) has role EC 2.7.11.22 (cyclin-dependent kinase) inhibitor (CHEBI:82665) olomoucine (CHEBI:44661) is a 2,6-diaminopurines (CHEBI:38001) olomoucine (CHEBI:44661) is a ethanolamines (CHEBI:23981)

IUPAC Name

2-{[6-(benzylamino)-9-methyl-9H-purin-2-yl]amino}ethanol

Synonyms	Sources
2-(2-hydroxyethylamino)-6-(benzylamino)-9-methylpurine	ChemIDplus
2-(hydroxyethylamino)-6-benzylamino-9-methylpurine	ChEBI
2-[[9-methyl-6-[(phenylmethyl)amino]-9H-purin-2-yl]amino]-ethanol	ChEBI
2-{[6-(benzylamino)-9-methyl-9H-purin-2-yl]amino}ethan-1-ol	IUPAC
6-(benzylamino)-2-(2-hydroxyethylamino)-9-methylpurine	ChEBI
olomucine	LINCS

Manual Xrefs	Databases
CPD-5442	MetaCyc
DB02116	DrugBank
FDB013890	FooDB
HMDB0035233	HMDB
LSM-3857	LINCS
OLO	PDBeChem
View more database links

Registry Number	Type	Source
101622-51-9	CAS Registry Number	ChemIDplus

Citations

Zhou Y, Zeng YP, Zhou Q, Guan JX, Lu ZN (2016)
The effect of cyclin-dependent kinases inhibitor treatment on experimental herpes simplex encephalitis mice.
Neuroscience letters 627, 71-76 [PubMed:27241721]
[show Abstract]

Tsou YC, Wang HH, Hsieh CC, Sun KH, Sun GH, Jhou RS, Lin TI, Lu SY, Liu HY, Tang SJ (2016)
Down-regulation of BNIP3 by olomoucine, a CDK inhibitor, reduces LPS- and NO-induced cell death in BV2 microglial cells.
Neuroscience letters 628, 186-193 [PubMed:27345388]
[show Abstract]

Chen L, Li J, Wu L, Yang M, Gao F, Yuan L (2014)
Synergistic actions of olomoucine and bone morphogenetic protein-4 in axonal repair after acute spinal cord contusion.
Neural regeneration research 9, 1830-1838 [PubMed:25422646]
[show Abstract]

Wandl S, Wesierska-Gadek J (2009)
Is olomoucine, a weak CDK2 inhibitor, able to induce apoptosis in cancer cells?
Annals of the New York Academy of Sciences 1171, 242-249 [PubMed:19723061]
[show Abstract]

Tripathi BK, Stepp MA, Gao CY, Zelenka PS (2008)
The Cdk5 inhibitor olomoucine promotes corneal debridement wound closure in vivo.
Molecular vision 14, 542-549 [PubMed:18385789]
[show Abstract]

Boutis A, Papazisis K, Pistevou-Gompaki K, Lambropoulos A, Sofroniadis I, Papageorgiou A, Destouni E, Kortsaris A (2006)
Cyclin-dependent kinase (CDK) inhibitor olomoucine enhances gamma-irradiation-induced apoptosis and cell cycle arrest in Raji cells.
Anticancer research 26, 3493-3498 [PubMed:17094472]
[show Abstract]

Mad'arová J, Lukesová M, Hlobilková A, Strnad M, Vojtesek B, Lenobel R, Hajdúch M, Murray PG, Perera S, Kolár Z (2002)
Synthetic inhibitors of CDKs induce different responses in androgen sensitive and androgen insensitive prostatic cancer cell lines.
Molecular pathology : MP 55, 227-234 [PubMed:12147712]
[show Abstract]

Abraham RT, Acquarone M, Andersen A, Asensi A, Bellé R, Berger F, Bergounioux C, Brunn G, Buquet-Fagot C, Fagot D (1995)
Cellular effects of olomoucine, an inhibitor of cyclin-dependent kinases.
Biology of the cell 83, 105-120 [PubMed:7549905]
[show Abstract]
Olomoucine (2-(2-hydroxyethylamino)-6-benzylamino-9-methylpurine) has been recently described as a competitive inhibitor (ATP-binding site) of the cell cycle regulating p34cdc2/cyclin B, p33cdk2/cyclin A and p33cdk2/cyclin E kinases, the brain p33cdk5/p35 kinase and the ERK1/MAP-kinase. The unusual specificity of this compound towards cell cycle regulating enzymes suggests that it could inhibit certain steps of the cell cycle. The cellular effects of olomoucine were investigated in a large variety of plant and animal models. This compound inhibits the G1/S transition of unicellular algae (dinoflagellate and diatom). It blocks Fucus zygote cleavage and development of Laminaria gametophytes. Stimulated Petunia mesophyl protoplasts are arrested in G1 by olomoucine. By arresting cleavage it blocks the Laminaria gametophytes. Stimulated Petunia mesophyl protoplasts are arrested in G1 by olomoucine. By arresting cleavage it blocks the development of Calanus copepod larvae. It reversibly inhibits the early cleavages of Caenorhabditis elegans embryos and those of ascidian embryos. Olomoucine inhibits the serotonin-induced prophase/metaphase transition of clam oocytes; furthermore, it triggers the the release of these oocytes from their meiotic metaphase I arrest, and induces nuclei reformation. Olomoucine slows down the prophase/metaphase transition in cleaving sea urchin embryos, but does not affect the duration of the metaphase/anaphase and anaphase/telophase transitions. It also inhibits the prophase/metaphase transition of starfish oocytes triggered by various agonists. Xenopus oocyte maturation, the in vivo and in vitro phosphorylation of elongation factor EF-1 are inhibited by olomoucine. Mouse oocyte maturation is delayed by this compound, whereas parthenogenetic release from metaphase II arrest is facilitated. Growth of a variety of human cell lines (rhabdomyosarcoma cell lines Rh1, Rh18, Rh28 and Rh30; MCF-7, KB-3-1 and their adriamycin-resistant counterparts; National Cancer Institute 60 human tumor cell lines comprising nine tumor types) is inhibited by olomoucine. Cell cycle parameter analysis of the non-small cell lung cancer cell line MR65 shows that olomoucine affects G1 and S phase transits. Olomoucine inhibits DNA synthesis in interleukin-2-stimulated T lymphocytes (CTLL-2 cells) and triggers a G1 arrest similar to interleukin-2 deprivation. Both cdc2 and cdk2 kinases (immunoprecipitated from nocodazole- and hydroxyurea-treated CTLL-2 cells, respectively) are inhibited by olomoucine. Both yeast and Drosophila embryos were insensitive to olomoucine. Taken together the results of this Noah's Ark approach show that olomoucine arrests cells both at the G1/S and the G2/M boundaries, consistent with the hypothesis of a prevalent effect on the cdk2 and cdc2 kinases, respectively.

Veselý J, Havlicek L, Strnad M, Blow JJ, Donella-Deana A, Pinna L, Letham DS, Kato J, Detivaud L, Leclerc S (1994)
Inhibition of cyclin-dependent kinases by purine analogues.
European journal of biochemistry 224, 771-786 [PubMed:7925396]
[show Abstract]
While testing purines related to the non-specific protein kinase inhibitors N6-dimethylaminopurine and N6-(delta 2-isopentenyl)adenine as potential inhibitors of the p34cdc2/cyclin B kinase, we discovered a compound with high specificity, 2-(2-hydroxyethylamino)-6- benzylamino-9-methylpurine (olomoucine). Kinetic analysis of kinase inhibition reveals that olomoucine behaves as a competitive inhibitor for ATP and as a non-competitive inhibitor for histone H1 (linear inhibition for both substrates). The kinase specificity of this inhibition was investigated for 35 highly purified kinases (including p34cdk4/cyclin D1, p40cdk6/cyclin D3, cAMP-dependent and cGMP-dependent kinases, eight protein kinase C isoforms, calmodulin-dependent kinase II, myosin light-chain kinase, mitogen-activated S6 kinase, casein kinase 2, double-stranded RNA-activated protein kinase, AMP-stimulated kinase, eight tyrosine kinases). Most kinases are not significantly inhibited. Only the cell-cycle regulating p34cdc2/cyclin B, p33cdk2/cyclin A and p33cdk2/cyclin E kinases, the brain p33cdk5/p35 kinase and the ERK1/MAP-kinase (and its starfish homologue p44mpk) are substantially inhibited by olomoucine (IC50 values are 7, 7, 7, 3 and 25 microM, respectively). The cdk4/cyclin D1 and cdk6/cyclin D3 kinases are not significantly sensitive to olomoucine (IC50 values greater than 1 mM and 150 microM, respectively). N6-(delta 2-Isopentenyl)adenine is confirmed as a general kinase inhibitor with IC50 values of 50-100 microM for many kinases. The purine specificity of cyclin-dependent kinase inhibition was investigated: among 81 purine derivatives tested, only C2, N6 and N9-substituted purines exert a strong inhibitory effect on the p34cdc2/cyclin B kinase. An essentially similar sensitivity to this olomoucine family of compounds was observed for the brain-specific cdk5/p35 kinase. Structure/activity relationship studies allow speculation on the interactions of olomoucine and its analogues with the kinase catalytic subunit. Olomoucine inhibits in vitro M-phase-promoting factor activity in metaphase-arrested Xenopus egg extracts, inhibits in vitro DNA synthesis in Xenopus interphase egg extracts and inhibits the licensing factor, an essential replication factor ensuring that DNA is replicated only once in each cell cycle. Olomoucine inhibits the starfish oocyte G2/M transition in vivo. Through its unique selectivity olomoucine provides an anti-mitotic reagent that may preferentially inhibit certain steps of the cell cycle.

Glab N, Labidi B, Qin LX, Trehin C, Bergounioux C, Meijer L (1994)
Olomoucine, an inhibitor of the cdc2/cdk2 kinases activity, blocks plant cells at the G1 to S and G2 to M cell cycle transitions.
FEBS letters 353, 207-211 [PubMed:7523194]
[show Abstract]

Last Modified

30 October 2019

ChEBI

CHEBI:44661 - olomoucine

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