PI3Kα Inhibitor

LOXO-783

PI3Kα Inhibitor

Gkeka P, et al1; Karakas B, et al2; Vasan N, et al3

Target
Phosphoinositide 3-kinase alpha (PI3Kα) H1047R mutations are activating oncogenic events that occur in ~15% of breast cancers and less commonly in other cancers.
Molecule
LOXO-783 is a potent, highly mutant-selective, brain-penetrant, allosteric small molecule PI3Kα H1047R inhibitor. LOXO-783 has shown preclinical activity without on-target wild-type PI3Kα mediated toxicity.5
Clinical Development
LOXO-783 is being investigated in an open-label, multicenter, phase 1a/1b study in patients with PIK3CA H1047R-mutant advanced breast cancer and other solid tumors.

References

  1. Gkeka P, et al. PLoS Comput Biol. 2014;10(10):e1003895.
  2. Karakas B, et al. Br J Cancer. 2006;94(4):455-459.
  3. Vasan N, et al. Ann Oncol. 2019;30(Suppl_10):x3–x11.
  4. Samuels Y, et al. Science. 2004;304(5670):554.
  5. Klippel A, et al. Preclinical characterization of LOXO-783 (LOX-22783), a highly potent, mutant-selective, and brain-penetrant allosteric PI3Kα H1047R inhibitor. Presented at AACR-NCI-EORTC Virtual Meeting 2021; October 7, 2021.
Clinical Development
LOXO-783 is being investigated in an open-label, multicenter, phase 1a/1b study in patients with PIK3CA H1047R-mutant advanced breast cancer and other solid tumors.

References

  1. Gkeka P, et al. PLoS Comput Biol. 2014;10(10):e1003895.
  2. Karakas B, et al. Br J Cancer. 2006;94(4):455-459.
  3. Vasan N, et al. Ann Oncol. 2019;30(Suppl_10):x3–x11.
  4. Samuels Y, et al. Science. 2004;304(5670):554.
  5. Klippel A, et al. Preclinical characterization of LOXO-783 (LOX-22783), a highly potent, mutant-selective, and brain-penetrant allosteric PI3Kα H1047R inhibitor. Presented at AACR-NCI-EORTC Virtual Meeting 2021; October 7, 2021.

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

CDK4 & 6 Inhibitor

Learn More

BTK Inhibitor

Learn More

VEGF Receptor-2 Antagonist

Learn More