Tradipitant

Tradipitant
Legal status
Legal status	Investigational;
Identifiers
	IUPAC name (2-(1-(3,5-Bis(trifluoromethyl)benzyl)-5-(pyridin-4-yl)-1H-1,2,3-triazol-4-yl)pyridin-3-yl)(2-chlorophenyl)methanone;
CAS Number	622370-35-8;
PubChem CID	9916461;
ChemSpider	8092108;
Chemical and physical data
Formula	C28H16ClF6N5O
Molar mass	587.90 g/mol g·mol−1
3D model (JSmol)	Interactive image;
	SMILES Clc1ccccc1C(=O)c2c(nccc2)c3nnn(c3c4ccncc4)Cc5cc(cc(c5)C(F)(F)F)C(F)(F)F;
	InChI InChI=1S/C28H16ClF6N5O/c29-22-6-2-1-4-20(22)26(41)21-5-3-9-37-23(21)24-25(17-7-10-36-11-8-17)40(39-38-24)15-16-12-18(27(30,31)32)14-19(13-16)28(33,34)35/h1-14H,15H2; Key:CAVRKWRKTNINFF-UHFFFAOYSA-N;

Tradipitant (VLY-686 or LY686017) is an experimental drug that is a neurokinin 1 antagonist. It works by blocking substance P, a small signaling molecule. Originally, this compound was owned by Eli Lilly and named LY686017. VLY-686 was purchased by Vanda Pharmaceuticals from Eli Lilly and Company in 2012.^[1] Vanda Pharmaceuticals is a U.S. pharmaceutical company that as of November 2015 only has 3 drugs in their product pipeline: tasimelteon, VLY-686, and iloperidone.^[2]

Indications

Pruritus

It is being investigated by Vanda Pharmaceuticals for chronic pruritus (itchiness) in atopic dermatitis. In March 2015, Vanda announced positive results from a Phase II proof of concept study.^[3] A proof of concept study is done in early stage clinical trials after there have been promising preclinical results. It provides preliminary evidence that the drug is active in humans and has some efficacy.^[4]

Alcoholism

VLY-686 reduced alcohol craving in recently detoxified alcoholic patients as measured by the Alcohol Urge Questionnaire.^[5] In a placebo controlled clinical trial of recently detoxified alcoholic patients, VLY-686 significantly reduced alcohol craving as measured by the Alcohol Urge Questionnaire. It also reduced the cortisol increase seen after a stress test compared to placebo. The dose given was 50 mg per day.

Social anxiety disorder

In a 12-week randomized trial of LY68017 in 189 patients with social anxiety disorder, 50 mg of LY68017 did not provide any statistically significant improvement over placebo.^[6]

References

^ "Company Overview of Eli Lilly & Co., Worldwide License to Develop and Commercialize VLY-686". Bloomberg Business. Retrieved 16 November 2015.
^ [1]
^ "Vanda Pharmaceuticals Announces Tradipitant Phase II Proof of Concept Study Results for Chronic Pruritus in Atopic Dermatitis". PR Newswire. Retrieved 16 November 2015.
^ Schmidt, B (2006). "Proof of principle studies". Epilepsy Res. 68 (1): 48–52. doi:10.1016/j.eplepsyres.2005.09.019. PMID 16377153.
^ George, DT; Gilman, J; Hersh, J; et al. (2008). "Neurokinin 1 receptor antagonism as a possible therapy for alcoholism". Science. 6: 1536–1539. doi:10.2147/SAR.S70350. PMC 4567173. PMID 26379454.{{cite journal}}: CS1 maint: unflagged free DOI (link)
^ Tauscher, J; Kielbasa, W; Iyengar, S; et al. (2010). "Development of the 2nd generation neurokinin-1 receptor antagonist LY686017 for social anxiety disorder". European Neuropsychopharmacology. 20 (2): 80–87. doi:10.1016/j.euroneuro.2009.10.005. PMID 20018493.

Template:Neuropeptidergics

[1] "Company Overview of Eli Lilly & Co., Worldwide License to Develop and Commercialize VLY-686". Bloomberg Business. Retrieved 16 November 2015.

[2] [1]

[3] "Vanda Pharmaceuticals Announces Tradipitant Phase II Proof of Concept Study Results for Chronic Pruritus in Atopic Dermatitis". PR Newswire. Retrieved 16 November 2015.

[4] Schmidt, B (2006). "Proof of principle studies". Epilepsy Res. 68 (1): 48–52. doi:10.1016/j.eplepsyres.2005.09.019. PMID 16377153.

[5] George, DT; Gilman, J; Hersh, J; et al. (2008). "Neurokinin 1 receptor antagonism as a possible therapy for alcoholism". Science. 6: 1536–1539. doi:10.2147/SAR.S70350. PMC 4567173. PMID 26379454.{{cite journal}}: CS1 maint: unflagged free DOI (link)

[6] Tauscher, J; Kielbasa, W; Iyengar, S; et al. (2010). "Development of the 2nd generation neurokinin-1 receptor antagonist LY686017 for social anxiety disorder". European Neuropsychopharmacology. 20 (2): 80–87. doi:10.1016/j.euroneuro.2009.10.005. PMID 20018493.

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