KHS101 HCl

Description: KHS101 HCl is a novel, selective and synthetic small-molecule inhibitor of transforming acidic coiled-coil protein 3 (TACC3). KHS101 promoted tumor cell death in diverse GBM (glioblastoma multiforme) cell models, independent of their tumor subtype, and without affecting the viability of noncancerous brain cell lines. KHS101 exerted cytotoxic effects by disrupting the mitochondrial chaperone heat shock protein family D member 1 (HSPD1). In GBM cells, KHS101 promoted aggregation of proteins regulating mitochondrial integrity and energy metabolism. Mitochondrial bioenergetic capacity and glycolytic activity were selectively impaired in KHS101-treated GBM cells. In two intracranial patient-derived xenograft tumor models in mice, systemic administration of KHS101 reduced tumor growth and increased survival without discernible side effects. These findings suggest that targeting of HSPD1-dependent metabolic pathways might be an effective strategy for treating GBM.

References: Proc Natl Acad Sci U S A. 2010 Sep 21; 107(38):16542-7; Sci Transl Med. 2018 Aug 15; 10(454). pii: eaar2718.

Related CAS#:1262770-73-9 (free base)