This week in therapeutics

Indication

Target/marker/pathway

Summary

Licensing status

Publication and contact information

Cancer

Cancer

K-Ras; son of sevenless homolog 1 (SOS1); CRAF (RAF1)

In vitro, cell culture and mouse studies identified small molecule K-Ras inhibitors that could help treat cancer. Previous studies identified small molecules that bound to K-Ras and blocked its activation by SOS1. In the current study, structure-based drug discovery identified a new series of compounds that inhibited the interaction between GTP-bound K-Ras, RAF1 and SOS1. In mice with colon cancer cells driven by oncogenic K-Ras, the compounds decreased tumor growth compared with vehicle. Next steps include optimizing structures of the compounds and improving their potency.
Roche's Genentech Inc. has a discovery stage K-Ras inhibitor program (see Raising the Ras inhibitor bar, page 4).

SciBX 6(19); doi:10.1038/scibx.2013.465
Published online May 16, 2013

Patent application filed; available for licensing

Shima, F. et al. Proc. Natl. Acad. Sci. USA; published online
April 29, 2013;
doi:10.1073/pnas.1217730110
Contact: Tohru Kataoka,
Kobe University Graduate School of Medicine, Kobe, Japan
e-mail:
ataoka@people.kobe-u.ac.jp
Contact: Fumi Shima, same affiliation as above
e-mail:
sfumi@med.kobe-u.ac.jp