Ulotaront HCl | CAS#1310422-41-3 | TAAR1/5-HT1A agonist

MedKoo Cat#: 413039 | Name: Ulotaront HCl

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Description:

WARNING: This product is for research use only, not for human or veterinary use.

Ulotaront, also known as SEP-363856, and SEP-856, is a TAAR1/5-HT1A agonist. Ulotaront interacts with a small, common set of conserved residues within the TAAR1 and 5HT1A ligand-binding domain. Ulotaront is a compound of high solubility, high permeability, and low binding to plasma proteins. Ulotaront metabolism is mediated via both NADPH-dependent and NADPH-independent pathways, with CYP2D6 as the major metabolizing enzyme. Ulotaront is a promising agent for the treatment of schizophrenia with an apparent benign safety profile, which might provide a much-needed new and different treatment option for various domains of schizophrenia.

Chemical Structure

Ulotaront HCl

CAS#1310422-41-3 (HCl)

Theoretical Analysis

MedKoo Cat#: 413039

Name: Ulotaront HCl

CAS#: 1310422-41-3 (HCl)

Chemical Formula: C9H14ClNOS

Exact Mass: 0.0000

Molecular Weight: 219.73

Elemental Analysis: C, 49.20; H, 6.42; Cl, 16.13; N, 6.37; O, 7.28; S, 14.59

Price and Availability

Size	Price	Availability	Quantity
5mg	USD 450.00	2 Weeks
10mg	USD 750.00	2 Weeks

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Related CAS #

1310422-41-3 (HCl) 1310426-33-5 (free base) 2375116-24-6 (besylate) 2375116-27-9 (mesylate)

Synonym

Ulotaront HCl; Ulotaront hydrochloride; Ulotaront; SEP-856; SEP856; SEP 856; SEP-363856; SEP 363856; SEP363856;

IUPAC/Chemical Name

(7S)-4,7-Dihydro-N-methyl-5H-thieno[2,3-c]pyran-7-methanamine hydrochloride

InChi Key

JRDQGVVFSHRVTL-QRPNPIFTSA-N

InChi Code

InChI=1S/C9H13NOS.ClH/c1-10-6-8-9-7(2-4-11-8)3-5-12-9;/h3,5,8,10H,2,4,6H2,1H3;1H/t8-;/m0./s1

SMILES Code

CNC[C@H]1C2=C(C=CS2)CCO1.[H]Cl

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

Ulotaront HCl is a CNS active psychotropic agent with a unique, non-D2/5-HT2A mechanism of action and exerts antipsychotic-like effects.

In vitro activity:

This study compared ulotaront and ralmitaront at TAAR1, 5-HT1AR, and dopamine D2 using luciferase complementation-based G protein recruitment, cAMP accumulation, and G protein-coupled inward rectifier potassium channel activation assays. Compared to ralmitaront, ulotaront showed higher efficacy and faster kinetics at TAAR1 and had better efficacy at 5-HT1AR. Reference: Int J Neuropsychopharmacol. 2023 Sep 25;26(9):599-606. https://pubmed.ncbi.nlm.nih.gov/37549917/

In vivo activity:

Ulotaront may have under-studied effects on sleep quality. Both 25 mg and 50 mg doses of ulotaront acutely reduced nighttime REM sleep compared to placebo. Ulotaront at both doses also decreased the mean number of short-onset REM periods during the daytime multiple sleep latency test. Ulotaront did influence REM sleep, but it did not show a significant improvement in symptoms, such as cataplexy events or sleepiness when compared to a placebo. Reference: Sleep Med. 2023 Jul;107:202-211. https://pubmed.ncbi.nlm.nih.gov/37209427/

	Solvent	mg/mL	mM
Solubility
	DMSO	65.2	284.44
	Water	100.0	455.10

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 219.73 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Ågren R, Betari N, Saarinen M, Zeberg H, Svenningsson P, Sahlholm K. In Vitro Comparison of Ulotaront (SEP-363856) and Ralmitaront (RO6889450): Two TAAR1 Agonist Candidate Antipsychotics. Int J Neuropsychopharmacol. 2023 Sep 25;26(9):599-606. doi: 10.1093/ijnp/pyad049. PMID: 37549917; PMCID: PMC10519813. 2. Tsukada H, Chen YL, Xiao G, Lennek L, Milanovic SM, Worden M, Polhamus DG, Chiu YY, Hopkins SC, Galluppi GR. A Phase I, Open-Label, Fixed Sequence Study to Investigate the Effect of Cytochrome P450 2D6 Inhibition on the Pharmacokinetics of Ulotaront in Healthy Subjects. Clin Pharmacokinet. 2023 Dec;62(12):1755-1763. doi: 10.1007/s40262-023-01317-4. Epub 2023 Oct 26. PMID: 37882999; PMCID: PMC10684410. 3. Szabo ST, Hopkins SC, Lew R, Loebel A, Roth T, Koblan KS. A multicenter, double-blind, placebo-controlled, randomized, Phase 1b crossover trial comparing two doses of ulotaront with placebo in the treatment of narcolepsy-cataplexy. Sleep Med. 2023 Jul;107:202-211. doi: 10.1016/j.sleep.2023.04.019. Epub 2023 Apr 28. PMID: 37209427.

In vitro protocol:

In vivo protocol:

1. Tsukada H, Chen YL, Xiao G, Lennek L, Milanovic SM, Worden M, Polhamus DG, Chiu YY, Hopkins SC, Galluppi GR. A Phase I, Open-Label, Fixed Sequence Study to Investigate the Effect of Cytochrome P450 2D6 Inhibition on the Pharmacokinetics of Ulotaront in Healthy Subjects. Clin Pharmacokinet. 2023 Dec;62(12):1755-1763. doi: 10.1007/s40262-023-01317-4. Epub 2023 Oct 26. PMID: 37882999; PMCID: PMC10684410. 2. Szabo ST, Hopkins SC, Lew R, Loebel A, Roth T, Koblan KS. A multicenter, double-blind, placebo-controlled, randomized, Phase 1b crossover trial comparing two doses of ulotaront with placebo in the treatment of narcolepsy-cataplexy. Sleep Med. 2023 Jul;107:202-211. doi: 10.1016/j.sleep.2023.04.019. Epub 2023 Apr 28. PMID: 37209427.

1: Feemster JC, Westerland SM, Gossard TR, Steele TA, Timm PC, Jagielski JT, Strainis E, McCarter SJ, Hopkins SC, Koblan KS, St Louis EK. Treatment with the novel TAAR1 agonist ulotaront is associated with reductions in quantitative polysomnographic REM sleep without atonia in healthy human subjects: Results of a post-hoc analysis. Sleep Med. 2023 Jan;101:578-586. doi: 10.1016/j.sleep.2022.11.022. Epub 2022 Nov 24. PMID: 36584503. 2: Højlund M, Correll CU. Ulotaront: a TAAR1/5-HT1A agonist in clinical development for the treatment of schizophrenia. Expert Opin Investig Drugs. 2022 Dec;31(12):1279-1290. doi: 10.1080/13543784.2022.2158811. Epub 2022 Dec 22. PMID: 36533396. 3: Saarinen M, Mantas I, Flais I, Ågren R, Sahlholm K, Millan MJ, Svenningsson P. Correction To: TAAR1 dependent and independent actions of the potential antipsychotic and dual TAAR1/5-HT1A receptor agonist SEP- 363856. Neuropsychopharmacology. 2022 Nov 29. doi: 10.1038/s41386-022-01504-0. Epub ahead of print. Erratum for: Neuropsychopharmacology. 2022 Dec;47(13):2319-2329. PMID: 36446929. 4: Rojas M, Chávez-Castillo M, Duran P, Ortega Á, Bautista-Sandoval MJ, Salazar J, Riaño-Garzón M, Chacín M, Medina-Ortiz O, Palmar J, Cudris-Torres L, Bermúdez V. Psychosis in Parkinson's Disease: Looking Beyond Dopaminergic Treatments. Curr Pharm Des. 2022;28(33):2725-2741. doi: 10.2174/1381612828666220428102802. PMID: 36321314. 5: Kane JM. A New Treatment Paradigm: Targeting Trace Amine-Associated Receptor 1 (TAAR1) in Schizophrenia. J Clin Psychopharmacol. 2022 Sep-Oct 01;42(5 Suppl 1):S1-S13. doi: 10.1097/JCP.0000000000001596. PMID: 36099402. 6: Kwan C, Huot P. An overview of the active clinical trials for Parkinson's disease psychosis. Neurodegener Dis Manag. 2022 Aug;12(4):165-170. doi: 10.2217/nmt-2022-0020. Epub 2022 May 20. PMID: 35592949. 7: Ren X, Xiong J, Liang L, Chen Y, Zhang G. The Potential Antidepressant Action of Duloxetine Co-Administered with the TAAR1 Receptor Agonist SEP-363856 in Mice. Molecules. 2022 Apr 25;27(9):2755. doi: 10.3390/molecules27092755. PMID: 35566106; PMCID: PMC9105920. 8: Xiao G, Chen YL, Dedic N, Xie L, Koblan KS, Galluppi GR. In Vitro ADME and Preclinical Pharmacokinetics of Ulotaront, a TAAR1/5-HT1A Receptor Agonist for the Treatment of Schizophrenia. Pharm Res. 2022 May;39(5):837-850. doi: 10.1007/s11095-022-03267-1. Epub 2022 Apr 28. PMID: 35484370; PMCID: PMC9160101. 9: Sparacino G, Verdolini N, Vieta E, Pacchiarotti I. Existing and emerging pharmacological approaches to the treatment of mania: A critical overview. Transl Psychiatry. 2022 Apr 23;12(1):169. doi: 10.1038/s41398-022-01928-8. PMID: 35461339; PMCID: PMC9035148. 10: Liang L, Ren X, Xu J, Ma Y, Xue Y, Zhuang T, Zhang G. Effect of Co-Treatment of Olanzapine with SEP-363856 in Mice Models of Schizophrenia. Molecules. 2022 Apr 14;27(8):2550. doi: 10.3390/molecules27082550. PMID: 35458749; PMCID: PMC9024832. 11: Correll CU, Abi-Dargham A, Howes O. Emerging Treatments in Schizophrenia. J Clin Psychiatry. 2022 Feb 15;83(1):SU21204IP1. doi: 10.4088/JCP.SU21204IP1. PMID: 35172048. 12: Heffernan MLR, Herman LW, Brown S, Jones PG, Shao L, Hewitt MC, Campbell JE, Dedic N, Hopkins SC, Koblan KS, Xie L. Ulotaront: A TAAR1 Agonist for the Treatment of Schizophrenia. ACS Med Chem Lett. 2021 Dec 6;13(1):92-98. doi: 10.1021/acsmedchemlett.1c00527. PMID: 35047111; PMCID: PMC8762745. 13: Synan C, Bowen C, Heal DJ, Froger-Colléaux C, Beardsley PM, Dedic N, Hopkins SC, Campbell U, Koblan KS. Ulotaront, a novel TAAR1 agonist with 5-HT1A agonist activity, lacks abuse liability and attenuates cocaine cue-induced relapse in rats. Drug Alcohol Depend. 2022 Feb 1;231:109261. doi: 10.1016/j.drugalcdep.2021.109261. Epub 2021 Dec 31. PMID: 35033729. 14: Dedic N, Dworak H, Zeni C, Rutigliano G, Howes OD. Therapeutic Potential of TAAR1 Agonists in Schizophrenia: Evidence from Preclinical Models and Clinical Studies. Int J Mol Sci. 2021 Dec 7;22(24):13185. doi: 10.3390/ijms222413185. PMID: 34947997; PMCID: PMC8704992. 15: Correll CU, Koblan KS, Hopkins SC, Li Y, Heather Dworak, Goldman R, Loebel A. Safety and effectiveness of ulotaront (SEP-363856) in schizophrenia: results of a 6-month, open-label extension study. NPJ Schizophr. 2021 Dec 9;7(1):63. doi: 10.1038/s41537-021-00190-z. PMID: 34887427; PMCID: PMC8660889. 16: Spoelstra SK, Bruggeman R, Knegtering H. Een antipsychoticum zonder dopaminereceptorblokkade? [An antipsychotic without dopamine receptor blockade?]. Tijdschr Psychiatr. 2021;63(11):804-809. Dutch. PMID: 34851520. 17: Pahwa M, Sleem A, Elsayed OH, Good ME, El-Mallakh RS. New Antipsychotic Medications in the Last Decade. Curr Psychiatry Rep. 2021 Nov 29;23(12):87. doi: 10.1007/s11920-021-01298-w. PMID: 34843030. 18: Lobo MC, Whitehurst TS, Kaar SJ, Howes OD. New and emerging treatments for schizophrenia: a narrative review of their pharmacology, efficacy and side effect profile relative to established antipsychotics. Neurosci Biobehav Rev. 2022 Jan;132:324-361. doi: 10.1016/j.neubiorev.2021.11.032. Epub 2021 Nov 24. PMID: 34838528. 19: Hopkins SC, Ogirala A, Worden M, Koblan KS. Depicting Safety Profile of TAAR1 Agonist Ulotaront Relative to Reactions Anticipated for a Dopamine D2-Based Pharmacological Class in FAERS. Clin Drug Investig. 2021 Dec;41(12):1067-1073. doi: 10.1007/s40261-021-01094-7. Epub 2021 Nov 9. PMID: 34751928; PMCID: PMC8626367. 20: Chen YL, Shi Y, LaFayette A, Shi L, Koblan KS, Galluppi GR. A sensitive LC- MS/MS method for simultaneous quantification of ulotaront and its N-desmethyl metabolite in human plasma and application to a clinical study. J Pharm Biomed Anal. 2022 Jan 5;207:114404. doi: 10.1016/j.jpba.2021.114404. Epub 2021 Oct 6. PMID: 34700199.