Palbociclib

From Proteopedia

(Redirected from Ibrance)

Palbociclib, sold under the brand name Ibrance among others, is a medication developed by Pfizer for the treatment of HR-positive and HER2-negative breast cancer. See also Palbociclib. It is a selective inhibitor of the cyclin-dependent kinases CDK4 and CDK6 (see also CDK4).^[1]^[2]

In the G1 phase of the cell cycle, mammalian cells must pass a checkpoint, known as the restriction point "R", in order to complete the cell cycle and divide. CDK4 and CDK6 complex with cyclin D drive the phosphorylation of the retinoblastoma protein, Rb, which allows the cell to pass R and commit to division. Regulation of one or more proteins involved in this checkpoint is lost in many cancers. However, by inhibiting CDK4/6, palbociclib ensures that the cyclin D-CDK4/6 complex cannot aid in phosphorylating Rb. This prevents the cell from passing R and exiting G1, and in turn from proceeding through the cell cycle.^[3]

The X-ray co-crystal structure of human CDK6 and Palbociclib (5l2i).

Palbociclib binding site.

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5330286

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5330286

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formula:"C24 H29 N7 O2"

mw:"447.5328"

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Palbociclib

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References

↑ Finn RS, Dering J, Conklin D, Kalous O, Cohen DJ, Desai AJ, Ginther C, Atefi M, Chen I, Fowst C, Los G, Slamon DJ. PD 0332991, a selective cyclin D kinase 4/6 inhibitor, preferentially inhibits proliferation of luminal estrogen receptor-positive human breast cancer cell lines in vitro. Breast Cancer Res. 2009;11(5):R77. PMID:19874578 doi:10.1186/bcr2419
↑ Rocca A, Farolfi A, Bravaccini S, Schirone A, Amadori D. Palbociclib (PD 0332991) : targeting the cell cycle machinery in breast cancer. Expert Opin Pharmacother. 2014 Feb;15(3):407-20. PMID:24369047 doi:10.1517/14656566.2014.870555
↑ Xu H, Yu S, Liu Q, Yuan X, Mani S, Pestell RG, Wu K. Recent advances of highly selective CDK4/6 inhibitors in breast cancer. J Hematol Oncol. 2017 Apr 24;10(1):97. PMID:28438180 doi:10.1186/s13045-017-0467-2

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Alexander Berchansky, Michal Harel

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Palbociclib

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