Oncology Pipeline

For more than 50 years, Lilly has been dedicated to delivering life-changing medicines and support to people living with cancer and those who care for them. Lilly is determined to build on this heritage and continue making life better for all those affected by cancer around the world. In 2019 Lilly created Loxo Oncology at Lilly, with the goal of rapidly delivering impactful new medicines for people with cancer. Our approach centers on creating new medicines that work in early clinical development and will matter to patients.

CDK4 & 6 Inhibitor

Abemaciclib, LY2835219

CDK4_&_6_Inhibitor_Abemaciclib

Shapiro GI1

Target
Many human tumors acquire alterations, which can lead to the activation of cyclin-dependent kinases (CDKs). These alterations include mutations that directly activate CDK4 & 6, gene amplifications, which increase expression of various protein activators such as D-type cyclins, as well as genetic losses, which reduce expression of protein inhibitors such as p16. These various mechanisms as well as loss of retinoblastoma (Rb) can lead to an enhanced proliferative potential by decreasing dependency on external growth factors and mitogenic signaling pathways, which are required to stimulate growth under normal conditions.2,3
Molecule
Abemaciclib (LY2835219) has been shown in vitro to be a selective ATP-competitive inhibitor of CDK4 & 6 kinase activity that prevents the phosphorylation and subsequent inactivation of the Rb tumor suppressor protein, thereby inducing G1 cell-cycle arrest and inhibition of cell proliferation.4,5
Clinical Development
Abemaciclib is being investigated in clinical trials in patients with breast cancer, pediatric cancer, or prostate cancer.

References

  1. Shapiro GI. J Clin Oncol. 2006;24(11):1770-1783.
  2. Kim JK, Diehl JA. J Cell Physiol. 2009;220(2):292-296.
  3. Choi YJ, Anders L. Oncogene. 2014;33(15):1890-1903.
  4. Dempsey JA, et al. AACR Annual Meeting; April 6-10, 2013; Washington, DC. Abstract LB122.
  5. Gelbert LM, et al. Invest New Drugs. 2014;32(5):825-837.

The safety and efficacy of the agents under investigation have not been established. There is no guarantee that the agents will receive regulatory approval and become commercially available for the uses being investigated.

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