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.

CDK7 Inhibitor

LY3405105

CDK7 Inhibitor

UniProt1; Tassan JP, et al2; Kwiatkowski N, et al3; Wang Y, et al4; Sansó M and Fisher RP5; Bradner JE, et al6; Rusan M, et al7; Choi YJ, et al8; Wang C, et al9; Zhang Z, et al10

Target
Many human cancers become dependent on upregulated gene expression to gain a competitive growth advantage. CDK7 is a cyclin-dependent kinase with a principal function of regulating global gene transcription.11 CDK7 is upregulated in certain cancers, particularly breast cancer, in comparison to normal cells.12 CDK7 may also participate in resistance of cancer cells to common cell-signaling therapies such as anti-HER2 therapy.13
Molecule
LY3405105 is an orally available inhibitor of CDK7 activity. It has been shown in vitro to bind covalently to CDK7 and prevent formation of the TFIIH complex, which is required to initiate transcription. This results in decreased global RNA transcription and causes cell death in sensitive tumors, but not normal cells.
Clinical Development
LY3405105 is being investigated in a clinical trial in patients with advanced solid tumors.

References

  1. UniProt (CDK7_HUMAN): ELIXIR Core Data Resource; 1996. Updated August 12, 2020. Accessed September 18, 2020. https://www.uniprot.org/uniprot/P50613. 2. Tassan JP, et al. J Cell Biol. 1994;127(2):467-478. 3. Kwiatkowski N, et al. Nature. 2014;511(7511):616-620. 4. Wang Y, et al. Cell. 2015;163(1):174-186. 5. Sansó M, Fisher RP. Transcription. 2013;4(4):146-152. 6. Bradner JE, et al. Cell. 2017;168(4):629-643. 7. Rusan M, et al. Cancer Discov. 2018;8(1):59-73. 8. Choi YJ, et al. Sci Rep. 2019;9(1):7193. 9. Wang C, et al. Cell Res. 2018;28(6):690-692. 10. Zhang Z, et al. Mol Cancer Ther. 2017;16(9):1739-1750. 11. Kelso TW, et al. Mol Cell Biol. 2014;34(19):3675-3688. 12. Patel H, et al. Clin Cancer Res. 2016;22(23):5929-5938. 13. Sun B, et al. Oncogene. 2020;39(1):50-63.

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.

DISCOVER OTHER MOLECULES

RET Inhibitor

Learn More

CD73 Inhibitor

Learn More

Selective ER Degrader

Learn More