Verucerfont

Verucerfont
Clinical data
Routes of; administration	Oral
ATC code	none;
Identifiers
	IUPAC name 3-(4-methoxy-2-methylphenyl)-2,5-dimethyl-N-[(1S)-1-(3-methyl-1,2,4-oxadiazol-5-yl)propyl]pyrazolo[1,5-a]pyrimidin-7-amine;
CAS Number	885220-61-1;
PubChem CID	11596613;
ChemSpider	28295024;
UNII	X60608B091;
KEGG	D09695;
CompTox Dashboard (EPA)	DTXSID501032013 ;
ECHA InfoCard	100.158.110
Chemical and physical data
Formula	C22H26N6O2
Molar mass	406.490 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CC[C@@H](c1nc(no1)C)Nc2cc(nc3n2nc(c3c4ccc(cc4C)OC)C)C;
	InChI InChI=1S/C22H26N6O2/c1-7-17(22-24-15(5)27-30-22)25-19-11-12(2)23-21-20(14(4)26-28(19)21)16-9-8-10-18(29-6)13(16)3/h8-11,17,25H,7H2,1-6H3/t17-/m0/s1; Key:NZQAFTPOKINLRY-KRWDZBQOSA-N;

Verucerfont (GSK-561,679) is a drug developed by GlaxoSmithKline which acts as a CRF-1 antagonist. Corticotropin releasing factor (CRF), also known as Corticotropin releasing hormone, is an endogenous peptide hormone which is released in response to various triggers such as chronic stress, and activates the two corticotropin-releasing hormone receptors CRH-1 and CRH-2. This then triggers the release of corticotropin (ACTH), another hormone which is involved in the physiological response to stress.

Verucerfont blocks the CRH-1 receptor, and so reduces ACTH release following chronic stress. It is under investigation as a potential treatment for alcoholism, as chronic stress is often a factor in both development of alcoholism and relapse in recovering alcoholics. It has shown promising results in animal studies.^[1] However, human trials have shown that while the neuroendocrine effects translate from animal models, the alcohol anti-craving effects do not.^[2]

References

^ Zorrilla EP, Heilig M, de Wit H, Shaham Y (March 2013). "Behavioral, biological, and chemical perspectives on targeting CRF(1) receptor antagonists to treat alcoholism". Drug and Alcohol Dependence. 128 (3): 175–86. doi:10.1016/j.drugalcdep.2012.12.017. PMC 3596012. PMID 23294766.
^ Schwandt ML, Cortes CR, Kwako LE, et al. (April 2016). "The CRF1 Antagonist Verucerfont in Anxious Alcohol-Dependent Women: Translation of Neuroendocrine, But not of Anti-Craving Effects". Neuropsychopharmacology. 41 (12): 2818–2829. doi:10.1038/npp.2016.61. PMC 5061889. PMID 27109623.

[1] Zorrilla EP, Heilig M, de Wit H, Shaham Y (March 2013). "Behavioral, biological, and chemical perspectives on targeting CRF(1) receptor antagonists to treat alcoholism". Drug and Alcohol Dependence. 128 (3): 175–86. doi:10.1016/j.drugalcdep.2012.12.017. PMC 3596012. PMID 23294766.

[2] Schwandt ML, Cortes CR, Kwako LE, et al. (April 2016). "The CRF1 Antagonist Verucerfont in Anxious Alcohol-Dependent Women: Translation of Neuroendocrine, But not of Anti-Craving Effects". Neuropsychopharmacology. 41 (12): 2818–2829. doi:10.1038/npp.2016.61. PMC 5061889. PMID 27109623.

[1]

[2]

See also

References