Syntheses and antitumor activities of N'1,N'3-dialkyl-N'1,N'3-di-(alkylcarbonothioyl) malonohydrazide: the discovery of elesclomol.
A series of N'(1),N'(3)-dialkyl-N'(1),N'(3)-di(alkylcarbonothioyl) malonohydrazides have been designed and synthesized as anticancer agents by targeting oxidative stress and Hsp70 induction. Structure-activity relationship (SAR) studies lead to the discovery of STA-4783 (elesclomol), a novel small molecule that has been evaluated in a number of clinical trials as an anticancer agent in combination with Taxol.
Synta Pharmaceuticals Corp, Lexington, MA 02421, USA. schen@syntapharma.com
Shoujun
S
Chen
Lijun
L
Sun
Keizo
K
Koya
Noriaki
N
Tatsuta
Zhiqiang
Z
Xia
Timothy
T
Korbut
Zhenjian
Z
Du
Jim
J
Wu
Guiqing
G
Liang
Jun
J
Jiang
Mitsunori
M
Ono
Dan
D
Zhou
Andrew
A
Sonderfan
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D006834:Hydrazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D008819:Mice, Nude; D008958:Models, Molecular; D008968:Molecular Conformation; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D017239:Paclitaxel / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000972:Antineoplastic Agents, Phytogenic; D006834:Hydrazines; C512195:elesclomol; D017239:Paclitaxel
Anticancer; Discovery; Elesclomol; Hsp70 induction; Oxidative stress; ROS; SAR; STA-4783; Taxol enhancer