Chemistry and biology of thyrotropin-releasing hormone (TRH) and its analogs.
Thyrotropin-releasing hormone (TRH), a hypothalamic orally active neuropeptide, has been manifested in a wide range of biological responses. Besides its central role in regulating the pituitary-thyroid axis by simulating the release of thyrotropin, TRH has considerable influence on the activity of a number of neurobiological systems. Due to the therapeutic potential of TRH to treat several CNS maladies, the development of CNS-selective and metabolically stable TRH analogs is an area of interest. TRH is known to elicit its biological response through two G-protein coupled receptors for TRH (namely, TRH-R1 and TRH-R2). The distinct distribution of TRH receptors in tissues has provided opportunity to discover receptor subtype-specific analogs, which would demonstrate high CNS activities, and are completely free of hormonal activities. In this review, an in-depth analysis of the chemistry and biology of TRH and its analogs is provided. Recent discoveries of TRH-R2 selective analogs, TRH super agonists, metabolically stable TRH analogs, and targeted delivery of TRH analogs have been also discussed.
Monga
Vikramdeep
V
Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, S.A.S. Nagar, Punjab 160 062, India.
Meena
Chhuttan L
CL
Kaur
Navneet
N
Jain
Rahul
R
D000818:Animals; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D018025:Receptors, Thyrotropin-Releasing Hormone / Q000378:metabolism; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000378:metabolism* / Q000494:pharmacology
D018025:Receptors, Thyrotropin-Releasing Hormone; D013973:Thyrotropin-Releasing Hormone