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PF-06873600 Sale

(Synonyms: PF-3600) 目录号 : GC32832

An inhibitor of Cdk2, Cdk4, and Cdk6

PF-06873600 Chemical Structure

Cas No.:2185857-97-8

规格 价格 库存 购买数量
10mM (in 1mL DMSO)
¥5,399.00
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5mg
¥4,909.00
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10mg
¥7,586.00
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25mg
¥15,619.00
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50mg
¥24,544.00
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100mg
¥35,254.00
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产品文档

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产品描述

PF-06873600 is an inhibitor of cyclin-dependent kinase 2 (Cdk2), Cdk4, and Cdk6 (Kis = 0.13, 1.25, and 0.11 nM, respectively).1 It is selective for these CDKs over Cdk1 and Cdk9 (Kis = 4.5 and 19.6 nM, respectively). PF-06873600 inhibits the phosphorylation of RB transcriptional corepressor 1 (RB1) in, and the proliferation of, OVCAR-3 ovarian cancer cells (EC50s = 19 and 45 nM, respectively). In vivo, PF-06873600 (30 mg/kg) reduces tumor volume in CTG-0464 and CTG-01912 non-small cell lung cancer (NSCLC) patient-derived xenograft (PDX) mouse models.

1.Freeman-Cook, K.D., Hoffman, R.L., Behenna, D.C., et al.Discovery of PF-06873600, a CDK2/4/6 inhibitor for the treatment of cancerJ. Med. Chem.64(13)9056-9077(2021)

Chemical Properties

Cas No. 2185857-97-8 SDF
别名 PF-3600
Canonical SMILES O=S(N1CCC(NC2=NC3=C(C=C(C(F)F)C(N3[C@@H]4CCC[C@]4(O)C)=O)C=N2)CC1)(C)=O
分子式 C20H27F2N5O4S 分子量 471.52
溶解度 DMSO : 83.33 mg/mL (176.73 mM) 储存条件 Store at -20°C
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1 mg 5 mg 10 mg
1 mM 2.1208 mL 10.604 mL 21.208 mL
5 mM 0.4242 mL 2.1208 mL 4.2416 mL
10 mM 0.2121 mL 1.0604 mL 2.1208 mL
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Research Update

Discovery of PF-06873600, a CDK2/4/6 Inhibitor for the Treatment of Cancer

J Med Chem 2021 Jul 8;64(13):9056-9077.PMID:34110834DOI:10.1021/acs.jmedchem.1c00159.

Control of the cell cycle through selective pharmacological inhibition of CDK4/6 has proven beneficial in the treatment of breast cancer. Extending this level of control to additional cell cycle CDK isoforms represents an opportunity to expand to additional tumor types and potentially provide benefits to patients that develop tumors resistant to selective CDK4/6 inhibitors. However, broad-spectrum CDK inhibitors have a long history of failure due to safety concerns. In this approach, we describe the use of structure-based drug design and Free-Wilson analysis to optimize a series of CDK2/4/6 inhibitors. Further, we detail the use of molecular dynamics simulations to provide insights into the basis for selectivity against CDK9. Based on overall potency, selectivity, and ADME profile, PF-06873600 (22) was identified as a candidate for the treatment of cancer and advanced to phase 1 clinical trials.

Expanding control of the tumor cell cycle with a CDK2/4/6 inhibitor

Cancer Cell 2021 Oct 11;39(10):1404-1421.e11.PMID:34520734DOI:10.1016/j.ccell.2021.08.009.

The CDK4/6 inhibitor, palbociclib (PAL), significantly improves progression-free survival in HR+/HER2- breast cancer when combined with anti-hormonals. We sought to discover PAL resistance mechanisms in preclinical models and through analysis of clinical transcriptome specimens, which coalesced on induction of MYC oncogene and Cyclin E/CDK2 activity. We propose that targeting the G1 kinases CDK2, CDK4, and CDK6 with a small-molecule overcomes resistance to CDK4/6 inhibition. We describe the pharmacodynamics and efficacy of PF-06873600 (PF3600), a pyridopyrimidine with potent inhibition of CDK2/4/6 activity and efficacy in multiple in vivo tumor models. Together with the clinical analysis, MYC activity predicts (PF3600) efficacy across multiple cell lineages. Finally, we find that CDK2/4/6 inhibition does not compromise tumor-specific immune checkpoint blockade responses in syngeneic models. We anticipate that (PF3600), currently in phase 1 clinical trials, offers a therapeutic option to cancer patients in whom CDK4/6 inhibition is insufficient to alter disease progression.

Restoring order at the cell cycle border: Co-targeting CDK4/6 and CDK2

Cancer Cell 2021 Oct 11;39(10):1302-1305.PMID:34506738DOI:10.1016/j.ccell.2021.08.007.

Overcoming resistance to CDK4/6 inhibitors is a major clinical challenge. In this issue of Cancer Cell, Freeman-Cook et al. study mechanisms of resistance to CDK4/6 inhibitors by employing a CRISPRa screen. They identify the cyclin E-CDK2 axis and Myc signaling as key pathways of resistance and develop PF-06873600, a selective CDK2/4/6 inhibitor.