Purvalanol A

Names

[ Name ]:
Purvalanol A

[Synonym ]:
P01
2-(1R-Isopropyl-2-hydroxyethylamino)-6-(3-chloroanilino)-9-isopropylpurine NG-60
(2R)-2-[[6-(3-chloroanilino)-9-propan-2-ylpurin-2-yl]amino]-3-methylbutan-1-ol
NG-60
(2R)-2-({6-[(3-Chlorophenyl)amino]-9-isopropyl-9H-purin-2-yl}amino)-3-methyl-1-butanol
(2R)-2-({6-[(3-Chlorophenyl)amino]-9-isopropyl-9H-purin-2-yl}amino)-3-methylbutan-1-ol
1-Butanol, 2-[[6-[(3-chlorophenyl)amino]-9-(1-methylethyl)-9H-purin-2-yl]amino]-3-methyl-, (2R)-
Purvalanol A
Purv

Biological Activity

[Description]:

Purvalanol A is a potent CDK inhibitor, which inhibits cdc2-cyclin B, cdk2-cyclin A, cdk2-cyclin E, cdk4-cyclin D1, and cdk5-p35 with IC50s of 4, 70, 35, 850, 75 nM, resepctively.

[Related Catalog]:

Signaling Pathways >> Autophagy >> Autophagy

Research Areas >> Cancer

[Target]

cdc2-cyclin B:4 nM (IC50)

cdk2-cyclin E:35 nM (IC50)

cdk2-cyclin A:70 nM (IC50)

cdk4-cyclin D1:850 nM (IC50)

cdk5-p35:75 nM (IC50)

erk1:9000 nM (IC50)

[In Vitro]

Purvalanol A inhibits cdc28 (S. cerevisiae) and erk1 with IC50s of 80 and 9000 nM. Purvalanol A shows inhibitory activities against the NCI panel of 60 human tumor cell lines, with average GI50 of 2 μM; two cell lines show an ∼20-fold increase in sensitivity to purvalanol A: the KM12 colon cancer cell line with a GI50 of 76 nM and the NCI-H522 non–small cell lung cancer cell line with a GI50 of 347 nM[1]. Purvalanol A is a 2.5-fold more potent inhibitor of CDK2, but also inhibits DYRK1A potently and a number of other protein kinases in the low micromolar range. Purvalanol A inhibits MKK1, MAPK2/ERK2, JNK/SAPK1c with IC50s of 80, 26, 84 μM[2]. Purvalanol A selectively inhibits the phosphorylation of cellular proteins. Purvalanol A prevents the increases of the contents of cyclins D and E during serum-induced G1 phase progression. Purvalanol A does not inhibit transcription under cell-free conditions[3].

[References]

[1]. Gray NS, et al. Exploiting chemical libraries, structure, and genomics in the search for kinase inhibitors. Science. 1998 Jul 24;281(5376):533-8.

[2]. Bain J, et al. The specificities of protein kinase inhibitors: an update. Biochem J. 2003 Apr 1;371(Pt 1):199-204.

[3]. Villerbu N, et al. Cellular effects of purvalanol A: a specific inhibitor of cyclin-dependent kinase activities. Int J Cancer. 2002 Feb 20;97(6):761-9.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.3±0.1 g/cm3

[ Boiling Point ]:
590.5±60.0 °C at 760 mmHg

[ Molecular Formula ]:
C₁₉H₂₅ClN₆O

[ Molecular Weight ]:
388.894

[ Flash Point ]:
310.9±32.9 °C

[ Exact Mass ]:
388.177826

[ PSA ]:
87.89000

[ LogP ]:
2.77

[ Vapour Pressure ]:
0.0±1.7 mmHg at 25°C

[ Index of Refraction ]:
1.654

[ Storage condition ]:
−20°C

[ Water Solubility ]:
methylene chloride: 50 mg/mL, clear, colorless

Safety Information

[ Personal Protective Equipment ]:
Eyeshields;Gloves;type N95 (US);type P1 (EN143) respirator filter

[ RIDADR ]:
NONH for all modes of transport

[ WGK Germany ]:
3

[ HS Code ]:
2933990090

Customs

[ HS Code ]: 2933990090

[ Summary ]:
2933990090. heterocyclic compounds with nitrogen hetero-atom(s) only. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

Articles

Phosphoproteomic Analysis of Aurora Kinase Inhibition in Monopolar Cytokinesis.

J. Proteome Res. 14 , 4087-98, (2015)

Cytokinesis is the last step of the cell cycle that requires coordinated activities of the microtubule cytoskeleton, actin cytoskeleton, and membrane compartments. Aurora B kinase is one of the master...

Involvement of atypical transcription factor E2F8 in the polyploidization during mouse and human decidualization.

Cell Cycle 14 , 1842-58, (2015)

Polyploid decidual cells are specifically differentiated cells during mouse uterine decidualization. However, little is known about the regulatory mechanism and physiological significance of polyploid...

KAP regulates ROCK2 and Cdk2 in an RNA-activated glioblastoma invasion pathway.

Oncogene 34(11) , 1432-41, (2015)

Aberrant splicing of the cyclin-dependent kinase-associated phosphatase, KAP, promotes glioblastoma invasion in a Cdc2-dependent manner. However, the mechanism by which this occurs is unknown. Here we...