Abemaciclib

Abemaciclib
Legal status
Legal status
  • Investigational
Identifiers
Synonyms LY2835219
CAS Number 1231929-97-7
PubChem (CID) 46220502
ChemSpider 29340700
ChEMBL CHEMBL3301610
PDB ligand ID 6ZV (PDBe, RCSB PDB)
Chemical and physical data
Formula C27H32F2N8
Molar mass 506.61 g·mol−1
3D model (Jmol) Interactive image

Abemaciclib (previously known as LY2835219) is a CDK inhibitor selective for CDK4 and CDK6.[1] It is an investigational drug for various types of cancer developed by Eli Lilly. It was designated as a breakthrough therapy by the U.S. Food and Drug Administration in October 2015.[2]

Clinical trials

Successful Phase I[3] and Phase II[4] trials against breast cancer were announced in May and December 2014 respectively.

As of early 2016 Abemaciclib is involved in 3 Phase III clinical trials:

Chemistry

Abemaciclib may be synthesized in a 4 step manner using a Suzuki coupling, followed by a Buchwald–Hartwig amination with the final step being a reductive amination using the Leuckart reaction.[10]

References

  1. ↑ Lu, Janice (13 August 2015). "Palbociclib: a first-in-class CDK4/CDK6 inhibitor for the treatment of hormone-receptor positive advanced breast cancer". Journal of Hematology & Oncology. 8 (1). doi:10.1186/s13045-015-0194-5.
  2. ↑ "FDA's Breakthrough Therapy Designation to Abemaciclib for Breast Cancer". Oncology Times. LWW Journals. Retrieved 30 March 2016.
  3. ↑ LY2835219 Shows Strong Single-Agent Activity in Preliminary Study in Metastatic Breast Cancer
  4. ↑ Clinical Activity of Abemaciclib (LY2835219), a Cell Cycle Inhibitor Selective for CDK4 and CDK6, in Patients with Relapsed or Refractory Mantle Cell Lymphoma
  5. ↑ Goldman, Jonathan W.; Shi, Peipei; Reck, Martin; Paz-Ares, Luis; Koustenis, Andrew; Hurt, Karla C. (January 2016). "Treatment Rationale and Study Design for the JUNIPER Study: A Randomized Phase III Study of Abemaciclib With Best Supportive Care Versus Erlotinib With Best Supportive Care in Patients With Stage IV Non–Small-Cell Lung Cancer With a Detectable KRAS Mutation Whose Disease Has Progressed After Platinum-Based Chemotherapy". Clinical Lung Cancer. 17 (1): 80–84. doi:10.1016/j.cllc.2015.08.003.
  6. ↑ Llombart, Antonio; Toi, Masakazu; Klise, Suzanne R; Frenzel, Martin; Chan, Edward M; Sledge, George W (30 April 2015). "Abstract OT1-1-07: A phase III study of abemaciclib (LY2835219) combined with fulvestrant in women with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) breast cancer (MONARCH 2)". Cancer Research. 75 (9 Supplement): OT1–1–07–OT1–1–07. doi:10.1158/1538-7445.SABCS14-OT1-1-07.
  7. ↑ A Study of Abemaciclib (LY2835219) Combined With Fulvestrant in Women With Hormone Receptor Positive HER2 Negative Breast Cancer (MONARCH 2)
  8. ↑ Goetz, Matthew P; Toi, Masakazu (2015). "MONARCH 3: A randomized phase III study of anastrozole or letrozole plus abemaciclib, a CDK4/6 inhibitor, or placebo in first-line treatment of women with HR+, HER2-locoregionally recurrent or metastatic breast cancer (MBC).". Journal of Clinical Oncology. 33 (No 15_suppl).
  9. ↑ A Study of Nonsteroidal Aromatase Inhibitors Plus Abemaciclib (LY2835219) in Postmenopausal Women With Breast Cancer (MONARCH 3)
  10. ↑ Frederick, Michael O.; Kjell, Douglas P. (February 2015). "A synthesis of abemaciclib utilizing a Leuckart–Wallach reaction". Tetrahedron Letters. 56 (7): 949–951. doi:10.1016/j.tetlet.2014.12.082.
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