Biomaterial Database

Thyrotropin-releasing hormone (TRH) analogues that exhibit selectivity to TRH receptor subtype 2. 2005

Navneet Kaur, and Xinping Lu, and Marvin C Gershengorn, and Rahul Jain

Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, Sector 67, S.A.S. Nagar--160 062, Punjab, India.

Thyrotropin-releasing hormone (TRH) analogues in which the C-2 position of the imidazole ring of the centrally placed histidine residue is substituted with various alkyl groups were synthesized and studied as agonists for TRH receptor subtype 1 (TRH-R1) and subtype 2 (TRH-R2). Several analogues were found to be selective agonists for TRH-R2 exhibiting no activation of TRH-R1. For example, analogue 4 (R= c-C3H5) was found to activate TRH-R2 with a potency (EC50) of 0.41 microM but did not activate TRH-R1 (potency > 100 microM). This study describes the first discovery of TRH-R2-specific agonists and provides impetus to design predominately CNS-effective TRH peptides.

UI	MeSH Term	Description	Entries
D007093	Imidazoles	Compounds containing 1,3-diazole, a five membered aromatic ring containing two nitrogen atoms separated by one of the carbons. Chemically reduced ones include IMIDAZOLINES and IMIDAZOLIDINES. Distinguish from 1,2-diazole (PYRAZOLES).
D002460	Cell Line	Established cell cultures that have the potential to propagate indefinitely.	Cell Lines,Line, Cell,Lines, Cell
D002491	Central Nervous System Agents	A class of drugs producing both physiological and psychological effects through a variety of mechanisms. They can be divided into "specific" agents, e.g., affecting an identifiable molecular mechanism unique to target cells bearing receptors for that agent, and "nonspecific" agents, those producing effects on different target cells and acting by diverse molecular mechanisms. Those with nonspecific mechanisms are generally further classed according to whether they produce behavioral depression or stimulation. Those with specific mechanisms are classed by locus of action or specific therapeutic use. (From Gilman AG, et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed, p252)	Central Nervous System Drugs
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D013329	Structure-Activity Relationship	The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.	Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D013973	Thyrotropin-Releasing Hormone	A tripeptide that stimulates the release of THYROTROPIN and PROLACTIN. It is synthesized by the neurons in the PARAVENTRICULAR NUCLEUS of the HYPOTHALAMUS. After being released into the pituitary portal circulation, TRH (was called TRF) stimulates the release of TSH and PRL from the ANTERIOR PITUITARY GLAND.	Protirelin,Thyroliberin,Abbott-38579,Antepan,Proterelin Tartrate,Proterelin Tartrate Hydrate,Protirelin Tartrate (1:1),Relefact TRH,Stimu-TSH,TRH Ferring,TRH Prem,Thypinone,Thyroliberin TRH Merck,Thyrotropin-Releasing Factor,Thyrotropin-Releasing Hormone Tartrate,Abbott 38579,Abbott38579,Hydrate, Proterelin Tartrate,Prem, TRH,Stimu TSH,StimuTSH,TRH, Relefact,Tartrate Hydrate, Proterelin,Thyrotropin Releasing Factor,Thyrotropin Releasing Hormone,Thyrotropin Releasing Hormone Tartrate
D018025	Receptors, Thyrotropin-Releasing Hormone	Cell surface receptors that bind thyrotropin releasing hormone (TRH) with high affinity and trigger intracellular changes which influence the behavior of cells. Activated TRH receptors in the anterior pituitary stimulate the release of thyrotropin (thyroid stimulating hormone, TSH); TRH receptors on neurons mediate neurotransmission by TRH.	Protirelin Receptors,Receptors, Protirelin,Receptors, TRH,Receptors, Thyroliberin,TRH Receptors,Thyroliberin Receptors,Thyrotropin Releasing Hormone Receptors,Protirelin Receptor,TRH Receptor,Thyrotropin Releasing Hormone Receptor,Receptor, Protirelin,Receptor, TRH,Receptors, Thyrotropin Releasing Hormone,Thyrotropin-Releasing Hormone Receptors