Novel anti-fatty acid synthase compounds with anti-cancer activity in HER2+ breast cancer.
Fatty acid synthase (FASN) expression and activity has emerged as a common phenotype in most human carcinomas, including breast cancer, and its expression is tightly linked to HER2 signaling pathways. The development of inhibitors of FASN activity has consequently appeared as a novel antitarget modality for treating cancer. However, the clinical use of FASN inhibitors, such as cerulenin, C75, and epigallocatechin 3-gallate (EGCG), is limited by anorexia and induced body weight loss or by its low in vivo potency and stability. Here, we summarize the design and development of G28UCM, the lead-compound of a novel family of synthetic FASN inhibitors, with both in vitro and in vivo activity in a human breast cancer model of FASN(+) and HER2(+) .
Institut d'Investigació Biomèdica de Girona - Facultat de Medicina, Girona, Spain.
G
G
Oliveras
A
A
Blancafort
A
A
Urruticoechea
O
O
Campuzano
D
D
Gómez-Cabello
R
R
Brugada
M L
ML
López-Rodríguez
R
R
Colomer
T
T
Puig
D016588:Anticarcinogenic Agents / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D002392:Catechin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002470:Cell Survival / Q000187:drug effects; D064429:Fatty Acid Synthases / Q000037:antagonists & inhibitors / Q000235:genetics*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*
D016588:Anticarcinogenic Agents; D000970:Antineoplastic Agents; D002392:Catechin; D064429:Fatty Acid Synthases; D018719:Erb-b2 Receptor Tyrosine Kinases; C045651:epigallocatechin gallate; C508053:ERBB2 protein, human