Abemaciclib, sold under the brand name Verzenio among others, is a medication for the treatment of advanced or metastatic breast cancers. It was developed by Eli Lilly and it acts as a CDK inhibitor selective for cyclin-dependent kinases CDK4 and CDK6.[1] See also Abemaciclib and CDK4.
Like the related drugs palbociclib and ribociclib, abemaciclib inhibits the enzymes cyclin-dependent kinase 4 (CDK4) and cyclin-dependent kinase 6 (CDK6).[2] These enzymes are responsible for phosphorylating and thus deactivating the retinoblastoma protein, which plays a role in cell cycle progression from the G1 (first gap) to the S (synthesis) phase.[3] Blocking this pathway prevents cells from progressing to the S phase, thereby inducing apoptosis (cell death).[2] In vitro analysis using cancer cell lines, it is reported that abemaciclib induces non‐apoptotic cell death characterized by formation of cytoplasmic vacuoles derived from lysosomes. This result suggests that there may be a mechanism of action other than inhibition of a cyclin-dependent kinase.[4]
The X-ray co-crystal structure of human CDK6 and Abemaciclib (5l2s).
Abemaciclib binding site. Water molecule is shown as red sphere.
- ↑ Lu J. Palbociclib: a first-in-class CDK4/CDK6 inhibitor for the treatment of hormone-receptor positive advanced breast cancer. J Hematol Oncol. 2015 Aug 13;8:98. PMID:26264704 doi:10.1186/s13045-015-0194-5
- ↑ 2.0 2.1 "Highlights of Prescribing Information for Verzenio" (PDF). September 2017. Archived (PDF) from the original on 5 September 2021. Retrieved 22 November 2017
- ↑ Goodrich DW, Wang NP, Qian YW, Lee EY, Lee WH. The retinoblastoma gene product regulates progression through the G1 phase of the cell cycle. Cell. 1991 Oct 18;67(2):293-302. PMID:1655277 doi:10.1016/0092-8674(91)90181-w
- ↑ Hino H, Iriyama N, Kokuba H, Kazama H, Moriya S, Takano N, Hiramoto M, Aizawa S, Miyazawa K. Abemaciclib induces atypical cell death in cancer cells characterized by formation of cytoplasmic vacuoles derived from lysosomes. Cancer Sci. 2020 Jun;111(6):2132-2145. PMID:32304130 doi:10.1111/cas.14419
