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Synthesis of potent antagonists of receptors for growth hormone-releasing hormone with antitumor and anti-inflammatory activity.
Cai, Renzhi; Zhang, Xianyang; Wang, Haibo; Cui, Tengjiao; Halmos, Gabor; Sha, Wei; He, Jinlin; Popovics, Petra; Vidaurre, Irving; Zhang, Chongxu; Mirsaeidi, Mehdi; Schally, Andrew V.
Afiliação
  • Cai R; Endocrine, Polypeptide, and Cancer Institute, Veterans Affairs Medical Center Miami, FL 33125, United States; South Florida VA Foundation for Research and Education, Veterans Affairs Medical Center Miami, FL 33125, United States.
  • Zhang X; Endocrine, Polypeptide, and Cancer Institute, Veterans Affairs Medical Center Miami, FL 33125, United States; Interdisciplinary Stem Cell Institute, Miller School of Medicine, University of Miami, Miami, FL 33136, United States.
  • Wang H; Endocrine, Polypeptide, and Cancer Institute, Veterans Affairs Medical Center Miami, FL 33125, United States; Interdisciplinary Stem Cell Institute, Miller School of Medicine, University of Miami, Miami, FL 33136, United States.
  • Cui T; Endocrine, Polypeptide, and Cancer Institute, Veterans Affairs Medical Center Miami, FL 33125, United States; South Florida VA Foundation for Research and Education, Veterans Affairs Medical Center Miami, FL 33125, United States; Department of Medicine, Divisions of Medical/Oncology and Endocrinolog
  • Halmos G; Department of Biopharmacy, School of Pharmacy, University of Debrecen, Hungary.
  • Sha W; Endocrine, Polypeptide, and Cancer Institute, Veterans Affairs Medical Center Miami, FL 33125, United States; Interdisciplinary Stem Cell Institute, Miller School of Medicine, University of Miami, Miami, FL 33136, United States.
  • He J; Endocrine, Polypeptide, and Cancer Institute, Veterans Affairs Medical Center Miami, FL 33125, United States; South Florida VA Foundation for Research and Education, Veterans Affairs Medical Center Miami, FL 33125, United States.
  • Popovics P; Endocrine, Polypeptide, and Cancer Institute, Veterans Affairs Medical Center Miami, FL 33125, United States.
  • Vidaurre I; Endocrine, Polypeptide, and Cancer Institute, Veterans Affairs Medical Center Miami, FL 33125, United States; South Florida VA Foundation for Research and Education, Veterans Affairs Medical Center Miami, FL 33125, United States.
  • Zhang C; Section of Pulmonary Veterans Affairs Medical Center Miami, FL 33125, United States.
  • Mirsaeidi M; Section of Pulmonary Veterans Affairs Medical Center Miami, FL 33125, United States; Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Miller School of Medicine, University of Miami, Miami, FL 33136, United States; Sylvester Comprehensive Cancer Center, Miller School of Medicine, Uni
  • Schally AV; Endocrine, Polypeptide, and Cancer Institute, Veterans Affairs Medical Center Miami, FL 33125, United States; South Florida VA Foundation for Research and Education, Veterans Affairs Medical Center Miami, FL 33125, United States; Department of Medicine, Divisions of Medical/Oncology and Endocrinolog
Peptides ; 150: 170716, 2022 04.
Article em En | MEDLINE | ID: mdl-34952135
The syntheses and biological evaluation of GHRH antagonists of AVR series with high anticancer and anti-inflammatory activities are described. Compared to our previously reported GHRH antagonist 602 of MIAMI series, AVR analogs contain additional modifications at positions 0, 6, 8, 10, 11, 12, 20, 21, 29 and 30, which induce greater antitumor activities. Five of nineteen tested AVR analogs presented binding affinities to the membrane GHRH receptors on human pituitary, 2-4-fold better than MIA-602. The antineoplastic properties of these analogs were evaluated in vitro using proliferation assays and in vivo in nude mice xenografted with various human cancer cell lines including lung (NSCLC-ADC HCC827 and NSCLC H460), gastric (NCI-N87), pancreatic (PANC-1 and CFPAC-1), colorectal (HT-29), breast (MX-1), glioblastoma (U87), ovarian (SK-OV-3 and OVCAR-3) and prostatic (PC3) cancers. In vitro AVR analogs showed inhibition of cell viability equal to or greater than MIA-602. After subcutaneous administration at 5 µg/day doses, some AVR antagonists demonstrated better inhibition of tumor growth in nude mice bearing various human cancers, with analog AVR-353 inducing stronger suppression than MIA-602 in lung, gastric, pancreatic and colorectal cancers and AVR-352 in ovarian cancers and glioblastoma. Both antagonists induced greater inhibition of GH release than MIA-602 in vitro in cultured rat pituitary cells and in vivo in rats. AVR-352 also demonstrated stronger anti-inflammatory effects in lung granulomas from mice with lung inflammation. Our studies demonstrate the merit of further investigation of AVR GHRH antagonists and support their potential use for clinical therapy of human cancers and other diseases.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Ovarianas / Glioblastoma / Neoplasias Pulmonares Limite: Animals / Female / Humans Idioma: En Revista: Peptides Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Ovarianas / Glioblastoma / Neoplasias Pulmonares Limite: Animals / Female / Humans Idioma: En Revista: Peptides Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos