This week in therapeutics

Indication

Target/marker/pathway

Summary

Licensing status

Publication and contact information

Cancer

Cancer

Baculoviral IAP repeat-
containing 2
(BIRC2; cIAP1); cIAP2 (BIRC3); diablo homolog (DIABLO; SMAC); X-linked inhibitor of apoptosis (XIAP)

Rodent and in vitro studies identified an orally bioavailable, bivalent SMAC mimetic that could help treat cancer. In vitro, the bivalent SMAC mimetic
SM-1200 bound to cIAP1, cIAP2 and XIAP and inhibited growth of human breast and ovarian cancer cell lines with nanomolar IC50 values. In rats, SM-1200 showed greater oral bioavailability than related bivalent mimetics. In a mouse xenograft model for human breast cancer, SM-1200 caused greater tumor regression than docetaxel. Next steps include in vivo studies to evaluate SM-1200 and related analogs as monotherapy or in combination with other drugs in cancer models.
Ascentage Pharma Group Corp. Ltd. and 3SBio Inc. have a multi-cIAP inhibitor in preclinical development to treat solid tumors.
At least seven companies have SMAC mimetics in
Phase II testing or earlier to treat various cancers.

SciBX 6(21); doi:10.1038/scibx.2013.512
Published online May 30, 2013

Patented by the University of Michigan; licensed to Ascentage Pharma Group

Sheng, R. et al. J. Med. Chem.; published online May 7, 2013;
doi:10.1021/jm400216d
Contact: Shaomeng Wang, University of Michigan, Ann Arbor, Mich.
e-mail:

shaomeng@umich.edu