TARGETING MYC driven malignancies:

OMT-001 & OMT-002

  • Increase of c-MYC protein stability via deactivation of GSK 3B through PI3K-Akt axis
  • Increase of c-MYC transcription by STAT5 by a largely unclear mechanism
  • Increase of c-MYC transcription via BRD4 activity

Hence, the ultimate c-MYC down-regulation as well as inactivation, calls for synergistic inhibition of the three processes.

JAK2/JAK2 (V617F), as an upstream player, regulating c-MYC protein turnover in many malignancies. This, appears to be a synergistic target along with BET and has the potential to preclude resistance to BET targeted therapy in cancer.

Funakoshi-Tago M, Sumi K, Kasahara T, Tago K (2013) Critical Roles of MYC-ODC Axis in the Cellular Transformation Induced by Myeloproliferative Neoplasm-Associated JAK2 V617F Mutant. PLoS ONE 8(1): e52844. 

Using Dual Prong Rational Technology (DPRT™) we have identified key dual inhibitor molecules (OMT-001; inhibiting BRD4 and JAK2) with excellent DMPK properties which exert near tumor elimination in leukemia xenograft models.