Cofttek holdings limited

CDK&Aurora kinase

PHA-848125 (802539-81-7)

PHA-848125 is a potent, ATP-competitive CDK inhibitor for CDK2 with IC50 of 45 nM. It is >3-fold more selective for CDK2 than CDK1, 2, 4, 5, and 7. Phase 2..

Not Intended for Therapeutic Use. For research use only.

CAS: 802539-81-7 Category

PHA-848125 (802539-81-7) Description

Milciclib, also known as PHA-848125 or PHA-848125AC, is an orally bioavailable inhibitor of cyclin-dependent kinases (CDKs) and thropomyosin receptor kinase A (TRKA), with potential antineoplastic activity. CDK2/TRKA inhibitor PHA-848125 AC potently inhibits cyclin-dependent kinase 2 (CDK2) and exhibits activity against other CDKs including CDK1 and CDK4, in addition to TRKA. Inhibition of these kinases may result in cell cycle arrest and apoptosis of tumor cells that express these kinases. CDKs are serine/threonine kinases involved in regulation of the cell cycle and may be overexpressed in some cancer cell types.

 

PHA-848125 (802539-81-7) Specifications

Product Name PHA-848125
Synonyms PHA-848125; PHA848125; PHA 848125; PHA-848125AC; PHA 848125AC; PHA848125AC; Milciclib.
Chemical Names N,1,4,4-tetramethyl-8-((4-(4-methylpiperazin-1-yl)phenyl)amino)-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
Purity ≥98% (HPLC)
CAS Number 802539-81-7
Molecular Formula C25H32N8O
Molecular Weight 460.57
Monoisotopic Mass 460.26991 g/mol
MDL number MFCD17169990
InChIKey RXZMYLDMFYNEIM-UHFFFAOYSA-N
InChi Code InChI=1S/C25H32N8O/c1-25(2)14-16-15-27-24(29-20(16)22-19(25)21(23(34)26-3)30-32(22)5)28-17-6-8-18(9-7-17)33-12-10-31(4)11-13-33/h6-9,15H,10-14H2,1-5H3,(H,26,34)(H,27,28,29)
SMILES O=C(C1=NN(C)C2=C1C(C (C)CC3=CN=C(NC4=CC=C(N5CCN(C)CC5)C=C4)N=C23)NC CC4CCO
Form Powder
Color N/A
Solubility  DMSO:85 mg/mL (184.6 mM);Ethanol:<1 mg/mL;Water:<1 mg/mL
Storage Temp.  −20°C
Shelf life >2 years if stored properly.
Handling Protect from air and light
Application A potent, ATP-competitive CDK inhibitor

 


=

RIDADR NONH for all modes of transport

References:

[1]. Degrassi A, Russo M, Nanni C, Patton V, Alzani R, Giusti AM, Fanti S, Ciomei M, Pesenti E, Texido G. Efficacy of PHA-848125, a cyclin-dependent kinase inhibitor, on the K-Ras(G12D)LA2 lung adenocarcinoma transgenic mouse model: evaluation by multimodality imaging. Mol Cancer Ther. 2010 Mar;9(3):673-81. Epub 2010 Mar 2. PubMed PMID: 20197397.

[2]. Caporali S, Alvino E, Starace G, Ciomei M, Brasca MG, Levati L, Garbin A, Castiglia D, Covaciu C, Bonmassar E, D’Atri S. The cyclin-dependent kinase inhibitor PHA-848125 suppresses the in vitro growth of human melanomas sensitive or resistant to temozolomide, and shows synergistic effects in combination with this triazene compound. Pharmacol Res. 2010 May;61(5):437-48. Epub 2009 Dec 21. PubMed PMID: 20026273.

[3]. Degrassi A, et al. Efficacy of PHA-848125, a cyclin-dependent kinase inhibitor, on the K-Ras(G12D)LA2 lung adenocarcinoma transgenic mouse model: evaluation by multimodality imaging. Mol Cancer Ther. 2010 Mar;9(3):673-81.

[4]. Tomillero A, Moral MA. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2009 Apr;31(3):183-226. PubMed PMID: 19536362.

[5]. the PTTG1 proto-oncogene contributes to the melanoma suppressive effects of the cyclin-dependent kinase inhibitor PHA-848125. Biochem Pharmacol. 2012 Sep 1;84(5):598-611.