Inhibition of Hsp47 by triphenylmethylamides induces apoptosis in melanoma

MEDI 15

Benjamin J. Leslie, bleslie@uiuc.edu, Department of Chemistry, The University of Illinois At Urbana-Champaign, Roger Adams Laboratory, 600 S. Mathews Ave Box 110-5, Urbana, IL 61801 and Paul J. Hergenrother, hergenro@uiuc.edu, Department of Chemistry, University of Illinois at Urbana-Champaign, 600 South Mathews Ave, Urbana, IL 61801.
Melanoma, cancer that arises from pigment-producing melanocytes, is the most aggressive and deadly form of skin cancer. Properties of parent melanocytes result in a cancer type that is notoriously resistant to anticancer drugs and has an extremely high propensity for metastasis. As traditional S- and M-phase arrestors are ineffective against melanoma, new protein targets are needed in order to combat this disease. We have recently discovered a class of small molecules, triphenylmethylamides (TPMAs), that potently induce G1 cell cycle arrest and apoptosis in cultured melanoma cells. We have used affinity chromatography followed by mass spectrometry based peptide identification to identify the molecular target of TPMAs. This presentation will detail recent findings that suggest that TPMAs bind to Hsp47 (a chaperone for (pro)collagen folding) in vitro and in vivo and that inhibition of Hsp47 leads to G1 arrest and apoptosis through induction of the unfolded protein response.
 

Medicinal Chemistry Award Symposium
1:30 PM-4:20 PM, Sunday, August 19, 2007 BCEC -- 210B, Oral

Division of Medicinal Chemistry

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007