PD0332991

• CAT Number: I004131
• CAS Number: 571190-30-2
• Molecular Formula: C24H29N7O2
• Molecular Weight: 447.53
• Purity: ≥95%
• Target: Cyclin-Dependent Kinases
• Solubility: DMSO: 0.2 mg/mL (Need ultrasonic or warming)
• Storage: Store at -20°C
• IUPAC Name: 6-acetyl-8-cyclopentyl-5-methyl-2-[(5-piperazin-1-ylpyridin-2-yl)amino]pyrido[2,3-d]pyrimidin-7-one
• InChI: InChI=1S/C24H29N7O2/c1-15-19-14-27-24(28-20-8-7-18(13-26-20)30-11-9-25-10-12-30)29-22(19)31(17-5-3-4-6-17)23(33)21(15)16(2)32/h7-8,13-14,17,25H,3-6,9-12H2,1-2H3,(H,26,27,28,29)
• InChIKey: AHJRHEGDXFFMBM-UHFFFAOYSA-N
• SMILES: CC1=C(C(=O)N(C2=NC(=NC=C12)NC3=NC=C(C=C3)N4CCNCC4)C5CCCC5)C(=O)C

PD0332991(CAT: I004131), also known as palbociclib, is a highly selective inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6). By inhibiting CDK4/6, PD0332991 prevents the phosphorylation of the retinoblastoma protein (Rb), thereby inhibiting the progression of the cell cycle from the G1 phase to the S phase. This results in cell cycle arrest and suppression of cell proliferation. PD0332991 has shown promising activity in the treatment of hormone receptor-positive, HER2-negative advanced breast cancer, both as monotherapy and in combination with endocrine therapy. It has also shown potential in other types of cancers, including lung cancer and lymphomas. Clinical studies have demonstrated its efficacy and safety profile, leading to its approval for certain indications.

Overview of Clinical Research

Palbociclib is a cyclin-dependent kinase 4 inhibitor as well as a cyclin-dependent kinase 6 inhibitor, which is marketed to treat breast caner.

Reference

[1]. Zhang, Cathy et al Advancing Bioluminescence Imaging Technology for the Evaluation of Anticancer Agents in the MDA-MB-435-HAL-Luc Mammary Fat Pad and Subrenal Capsule Tumor Models Clinical Cancer Research (2009), 15(1), 238-246.
[2]. Menu, Eline et al A Novel Therapeutic Combination Using PD 0332991 and Bortezomib: Study in the 5T33MM Myeloma Model Cancer Research (2008), 68(14), 5519-5523.
[3]. Schwartz GK, LoRusso PM, Dickson MA, Randolph SS, Shaik MN, Wilner KD, Courtney R, O/'Dwyer PJ.Phase I study of PD 0332991, a cyclin-dependent kinase inhibitor, administered in 3-week cycles (Schedule 2/1).Br J Cancer. 2011 Jun 7;104(12):1862-8.
[4]. Smith D, Tella M, Rahavendran SV, Shen Z.Quantitative analysis of PD 0332991 in mouse plasma using automated micro-sample processing and microbore liquid chromatography coupled with tandem mass spectrometry.J Chromatogr B Analyt Technol Biomed Life Sci. 2011 Oct 1;879(27):2860-5. Epub 2011 Aug 16.
[5]. Katsumi Y, Iehara T, Miyachi M, Yagyu S, Tsubai-Shimizu S, Kikuchi K, Tamura S, Kuwahara Y, Tsuchiya K, Kuroda H, Sugimoto T, Houghton PJ, Hosoi H.Sensitivity of malignant rhabdoid tumor cell lines to PD 0332991 is inversely correlated with p16 expression.Biochem Biophys Res Commun. 2011 Sep 16;413(1):62-8. Epub 2011 Aug 17.