Structure and Function of Small Non-Peptide CRF Antagonists and their Potential Clinical Use.
Corticotropin-releasing factor (CRF) can be considered a very important hormone or a chemical mediator. It works closely with other systems to regulate the manner through which the body may respond to stress. Thus it affects many biological processes associated with stress. Dysfunction of this system has also been correlated with various diseases such as major depression, anxiety, drug addiction and eating disorders. Rationally, this means that interfering with binding of CRF to its intended receptors can be an attractive target for drug design aiming at developing new medications for many ailments that are associated with stress such as depression, anxiety and stress-induced relapse in drug addiction. Hundreds of accounts of small molecule antagonists have appeared in the literature and the preclinical and clinical pharmacology have been reported for many of these agents. Several classes of small molecule CRF receptor antagonists which belong to the non-peptide class have been developed with many being widely used for research purposes. Currently several major pharmaceutical companies are pursuing development of small non-peptide CRF1 receptor antagonists. In this review article we explain the importance of development of non-peptide CRF antagonists and their clinical relevance with emphasis on those members that showed great promise or those that were advanced to clinical trials.
Department of Pharmaceutical Sciences, College of Pharmacy, South Dakota State University, Box 2202C, Brookings, SD 57007. United States.
Hesham
H
Fahmy
Department of Pharmaceutical Sciences, Chicago College of pharmacy, Midwestern University, Downers Grove, IL-60151. United States.
Bhimanna
B
Kuppast
Department of Pharmaceutical Sciences, College of Pharmacy, South Dakota State University, Brookings, South Dakota 57007. United States.
Mohamed Teleb
MT
Ismail
D000818:Animals; D001007:Anxiety / Q000188:drug therapy / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors* / Q000378:metabolism; D003863:Depression / Q000188:drug therapy / Q000378:metabolism; D003866:Depressive Disorder / Q000188:drug therapy / Q000378:metabolism; D055808:Drug Discovery / Q000379:methods; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods; D011724:Pyridazines / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D011743:Pyrimidines / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors* / Q000378:metabolism; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D019966:Substance-Related Disorders / Q000188:drug therapy / Q000378:metabolism; D013844:Thiazoles / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D014227:Triazines / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D000099052:CRF Receptor, Type 1
D011724:Pyridazines; D011743:Pyrimidines; D018019:Receptors, Corticotropin-Releasing Hormone; D054852:Small Molecule Libraries; D013844:Thiazoles; D014227:Triazines; D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone
CRF antagonists; anxiety; depression; drug addiction; hormone; pyrimidines