Abemaciclib metabolite M18  (Synonyms: LSN3106729)

Abemaciclib metabolite M18 (LSN3106729), the metabolite of Abemaciclib (HY-16297A), is a CDK inhibitor with antitumor activity. Abemaciclib metabolite M18 and a CRBN ligand have been used to design PROTAC CDK4/6 degrader^[1][2].

Abemaciclib metabolite M18 hydrochloride exhibits T_1/2 of 43.1 hr in plasma in healthy subjects^[3].
CDK4/6 inhibitors’ chief mechanism of action is inhibition of retinoblastoma (RB) protein phosphorylation and thus the induction of cell cycle arrest, CDK4/6 inhibitors alter cancer cell biology in other ways^[4].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

CDK4/6 inhibitors results T-cell persistence and immunologic memory increasing in mice receiving tumor-specific CD8⁺ T cells^[5].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

494.54

C₂₅H₂₈F₂N₈O

2704316-81-2

FC(C=N1)=C(C2=CC(N(C(C)C)C(CO)=N3)=C3C(F)=C2)N=C1NC4=NC=C(C=C4)CN5CCNCC5

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Edward S. Kim, et al. Abemaciclib in Combination with Single-Agent Options in Patients with Stage IV Non–Small Cell Lung Cancer: A Phase Ib Study.

  [2]. Nathanael Gray, et al. Degradation of cyclin-dependent kinase 4/6 (cdk4/6) by conjugation of cdk4/6 inhibitors with e3 ligase ligand and methods of use. WO2017185031A1.

  [3]. Palaniappan, et al. Abstract CT153: Pharmacokinetic drug interactions between abemaciclib and CYP3A inducers and inhibitors. Cancer Res. 2016-7-15; 76 (14_Supplement): CT153.

  [4]. Goel S, et al. CDK4/6 Inhibition in Cancer: Beyond Cell Cycle Arrest. Trends Cell Biol. 2018 Nov;28(11):911-925.  [Content Brief]

  [5]. Heckler M, et al. Inhibition of CDK4/6 Promotes CD8 T-cell Memory Formation. Cancer Discov. 2021 Oct;11(10):2564-2581.  [Content Brief]