Purushottamachar Puranik - Exploitation of multitarget prostate cancer clinical candidate VN/124-1 (TOK-001) to develop a novel class of androgen receptor down regulating agents for prostate cancer therapy

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  Publication Details (including relevant citation   information):

  242nd   ACS National Meeting held at Denver, Colorado, August 28 –   September 1, 2011. PAPER ID: MEDI-35


  The androgen receptor (AR) is a critical mediator of prostate   cancer (PC) proliferation at virtually all stages of PC,   including the dreaded castration-resistant stage. Selective AR   down-regulators (SARDs) reduce AR protein levels as well as block   AR activity and therefore are promising agents for the treatment   of PC. Our clinical candidate novel VN/124-1  (TOK-001) is a potent CYP17   inhibitor/antiandrogen with modest AR down-regulating activity   (EC50 ~ 10 µM). In the present study we used   VN/124-1 to conduct lead optimization to develop   a novel class of AR down-regulating agents. A series of new   compounds were designed, synthesized and evaluated for their   abilities to suppress AR expression in LNCaP cells and inhibition   of LNCaP cell viability by Western blot analysis and MTT assay,   respectively. Our design strategy involved systematic   modification of rings A, B or D; and modifications at C-3, C-16   and C-17 of our lead VN/124-1, resulted in novel   potent anti-PC agents.

  Address (URL): http://abstracts.acs.org/chem/242nm/program/divisionindex.php?act=presentations& val=General+Poster+Session&ses=General+Poster+Session&prog=62156