PSNCBAM-1 | CAS#877202-74-9 | CB1 receptor modulator

MedKoo Cat#: 329592 | Name: PSNCBAM-1

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Description:

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

PSNCBAM-1 is a CB1 receptor negative allosteric modulator (IC50 values are 45 and 209 nM) with hypophagic effects in vivo. PSNCBAM-1 allosteric antagonism may provide viable therapeutic alternatives to orthosteric CB(1) antagonists/inverse agonists in the treatment of CNS disease.

Chemical Structure

PSNCBAM-1

CAS#877202-74-9

Theoretical Analysis

MedKoo Cat#: 329592

Name: PSNCBAM-1

CAS#: 877202-74-9

Chemical Formula: C22H21ClN4O

Exact Mass: 392.1404

Molecular Weight: 392.89

Elemental Analysis: C, 67.26; H, 5.39; Cl, 9.02; N, 14.26; O, 4.07

Price and Availability

Size	Price	Availability	Quantity
5mg	USD 500.00	2 Weeks
25mg	USD 1,100.00	2 Weeks

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Synonym

PSNCBAM-1; PSNCBAM 1; PSNCBAM1.

IUPAC/Chemical Name

1-(4-chlorophenyl)-3-(3-(6-pyrrolidin-1-ylpyridin-2-yl)phenyl)urea

InChi Key

HDAYFSFWIPRJSO-UHFFFAOYSA-N

InChi Code

InChI=1S/C22H21ClN4O/c23-17-9-11-18(12-10-17)24-22(28)25-19-6-3-5-16(15-19)20-7-4-8-21(26-20)27-13-1-2-14-27/h3-12,15H,1-2,13-14H2,(H2,24,25,28)

SMILES Code

O=C(NC1=CC=CC(C2=NC(N3CCCC3)=CC=C2)=C1)NC4=CC=C(Cl)C=C4

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:

PSNCBAM-1 is a selective CB1 receptor negative allosteric modulator (CB1 NAM) with a strong preference for CB1 over CB2 receptors (IC50 = 74.3 and >10,000 nM, respectively). It inhibits CB1 receptor activation by various compounds, reduces food intake, and lowers body weight in rats at a 30 mg/kg dose. Additionally, at 10 mg/kg, it mitigates THC-induced effects in mice.

In vitro activity:

This study assessed the in vitro activity of PSNCBAM-1 and its analogs as allosteric modulators of the CB1 receptor. There were key substitutions important for CB1 receptor activity. The analogs showed potency similar to PSNCBAM-1 and increased specific binding of [(3)H]CP55,940. PSNCBAM-1 and two analogs dose-dependently reduced the Emax of the agonist curve in CB1 calcium mobilization assays, confirming their negative allosteric modulation properties. Reference: J Med Chem. 2014 Sep 25;57(18):7758-69. https://pubmed.ncbi.nlm.nih.gov/25162172/

In vivo activity:

In an acute rat feeding model, PSNCBAM-1 exhibited the capacity to reduce food intake and decrease body weight in rats. These findings highlight the practical in vivo effects of PSNCBAM-1, suggesting its potential as a therapeutic agent for conditions related to food intake and obesity. Reference: Br J Pharmacol. 2007 Nov;152(5):805-14. https://pubmed.ncbi.nlm.nih.gov/17592509/

	Solvent	mg/mL	mM
Solubility
	DMSO	39.3	100.00

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 392.89 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. German N, Decker AM, Gilmour BP, Gay EA, Wiley JL, Thomas BF, Zhang Y. Diarylureas as allosteric modulators of the cannabinoid CB1 receptor: structure-activity relationship studies on 1-(4-chlorophenyl)-3-{3-[6-(pyrrolidin-1-yl)pyridin-2-yl]phenyl}urea (PSNCBAM-1). J Med Chem. 2014 Sep 25;57(18):7758-69. doi: 10.1021/jm501042u. Epub 2014 Sep 4. PMID: 25162172; PMCID: PMC4175001. 2. Horswill JG, Bali U, Shaaban S, Keily JF, Jeevaratnam P, Babbs AJ, Reynet C, Wong Kai In P. PSNCBAM-1, a novel allosteric antagonist at cannabinoid CB1 receptors with hypophagic effects in rats. Br J Pharmacol. 2007 Nov;152(5):805-14. doi: 10.1038/sj.bjp.0707347. Epub 2007 Jun 25. PMID: 17592509; PMCID: PMC2190018.

In vitro protocol:

In vivo protocol:

1. Horswill JG, Bali U, Shaaban S, Keily JF, Jeevaratnam P, Babbs AJ, Reynet C, Wong Kai In P. PSNCBAM-1, a novel allosteric antagonist at cannabinoid CB1 receptors with hypophagic effects in rats. Br J Pharmacol. 2007 Nov;152(5):805-14. doi: 10.1038/sj.bjp.0707347. Epub 2007 Jun 25. PMID: 17592509; PMCID: PMC2190018.

1: Sanz-Martinez P, Tascher G, Cano-Franco S, Cabrerizo-Poveda P, Münch C, Homan EJ, Stolz A. GPCR Function in Autophagy Control: A Systematic Approach of Chemical Intervention. J Mol Biol. 2024 Aug 1;436(15):168643. doi: 10.1016/j.jmb.2024.168643. Epub 2024 Jun 5. PMID: 38848865. 2: Buechler HM, Sumi M, Madhuranthakam IM, Donegan C, DiGiorgio F Jr, Acosta AA, Uribe S, Rahman MA, Sorbello A, Fischer BD, Keck TM. The CB1 negative allosteric modulator PSNCBAM-1 reduces ethanol self-administration via a nonspecific hypophagic effect. Pharmacol Biochem Behav. 2024 Jul;240:173776. doi: 10.1016/j.pbb.2024.173776. Epub 2024 Apr 27. PMID: 38679080. 3: Flavin A, Azizi P, Murataeva N, Yust K, Du W, Ross R, Greig I, Nguyen T, Zhang Y, Mackie K, Straiker A. CB1 Receptor Negative Allosteric Modulators as a Potential Tool to Reverse Cannabinoid Toxicity. Molecules. 2024 Apr 20;29(8):1881. doi: 10.3390/molecules29081881. PMID: 38675703; PMCID: PMC11053441. 4: Nguyen T, Gamage TF, Decker AM, Finlay DB, Langston TL, Barrus D, Glass M, Harris DL, Zhang Y. Rational design of cannabinoid type-1 receptor allosteric modulators: Org27569 and PSNCBAM-1 hybrids. Bioorg Med Chem. 2021 Jul 1;41:116215. doi: 10.1016/j.bmc.2021.116215. Epub 2021 May 12. PMID: 34015703; PMCID: PMC8506265. 5: Meini S, Gado F, Stevenson LA, Digiacomo M, Saba A, Codini S, Macchia M, Pertwee RG, Bertini S, Manera C. PSNCBAM-1 analogs: Structural evolutions and allosteric properties at cannabinoid CB1 receptor. Eur J Med Chem. 2020 Oct 1;203:112606. doi: 10.1016/j.ejmech.2020.112606. Epub 2020 Jul 12. PMID: 32682199. 6: Dopart R, Immadi SS, Lu D, Kendall DA. Structural Optimization of the Diarylurea PSNCBAM-1, an Allosteric Modulator of Cannabinoid Receptor 1. Curr Ther Res Clin Exp. 2019 Dec 24;92:100574. doi: 10.1016/j.curtheres.2019.100574. PMID: 32021660; PMCID: PMC6994307. 7: Dopart R, Kendall DA. Allosteric modulators restore orthosteric agonist binding to mutated CB1 receptors. J Pharm Pharmacol. 2020 Jan;72(1):84-91. doi: 10.1111/jphp.13193. Epub 2019 Nov 13. PMID: 31722122; PMCID: PMC6906232. 8: Nguyen T, Gamage TF, Decker AM, Barrus D, Langston TL, Li JX, Thomas BF, Zhang Y. Synthesis and Pharmacological Evaluation of 1-Phenyl-3-Thiophenylurea Derivatives as Cannabinoid Type-1 Receptor Allosteric Modulators. J Med Chem. 2019 Nov 14;62(21):9806-9823. doi: 10.1021/acs.jmedchem.9b01161. Epub 2019 Oct 24. PMID: 31596583; PMCID: PMC6953423. 9: Jagla CAD, Scott CE, Tang Y, Qiao C, Mateo-Semidey GE, Yudowski GA, Lu D, Kendall DA. Pyrimidinyl Biphenylureas Act as Allosteric Modulators to Activate Cannabinoid Receptor 1 and Initiate β-Arrestin-Dependent Responses. Mol Pharmacol. 2019 Jan;95(1):1-10. doi: 10.1124/mol.118.112854. Epub 2018 Oct 15. PMID: 30322873; PMCID: PMC6277924. 10: Nguyen T, Gamage TF, Decker AM, German N, Langston TL, Farquhar CE, Kenakin TP, Wiley JL, Thomas BF, Zhang Y. Diarylureas Containing 5-Membered Heterocycles as CB1 Receptor Allosteric Modulators: Design, Synthesis, and Pharmacological Evaluation. ACS Chem Neurosci. 2019 Jan 16;10(1):518-527. doi: 10.1021/acschemneuro.8b00396. Epub 2018 Sep 20. PMID: 30188693; PMCID: PMC6426682. 11: Alaverdashvili M, Laprairie RB. The future of type 1 cannabinoid receptor allosteric ligands. Drug Metab Rev. 2018 Feb;50(1):14-25. doi: 10.1080/03602532.2018.1428341. Epub 2018 Jan 21. PMID: 29355038. 12: Dopart R, Lu D, Lichtman AH, Kendall DA. Allosteric modulators of cannabinoid receptor 1: developing compounds for improved specificity. Drug Metab Rev. 2018 Feb;50(1):3-13. doi: 10.1080/03602532.2018.1428342. Epub 2018 Jan 21. PMID: 29355030; PMCID: PMC6134837. 13: Bertini S, Chicca A, Gado F, Arena C, Nieri D, Digiacomo M, Saccomanni G, Zhao P, Abood ME, Macchia M, Gertsch J, Manera C. Novel analogs of PSNCBAM-1 as allosteric modulators of cannabinoid CB1 receptor. Bioorg Med Chem. 2017 Dec 15;25(24):6427-6434. doi: 10.1016/j.bmc.2017.10.015. Epub 2017 Oct 16. PMID: 29079014; PMCID: PMC5794004. 14: Gamage TF, Farquhar CE, Lefever TW, Thomas BF, Nguyen T, Zhang Y, Wiley JL. The great divide: Separation between in vitro and in vivo effects of PSNCBAM- based CB1 receptor allosteric modulators. Neuropharmacology. 2017 Oct;125:365-375. doi: 10.1016/j.neuropharm.2017.08.008. Epub 2017 Aug 10. PMID: 28803965; PMCID: PMC5771238. 15: Nguyen T, German N, Decker AM, Langston TL, Gamage TF, Farquhar CE, Li JX, Wiley JL, Thomas BF, Zhang Y. Novel Diarylurea Based Allosteric Modulators of the Cannabinoid CB1 Receptor: Evaluation of Importance of 6-Pyrrolidinylpyridinyl Substitution. J Med Chem. 2017 Sep 14;60(17):7410-7424. doi: 10.1021/acs.jmedchem.7b00707. Epub 2017 Aug 18. PMID: 28792219; PMCID: PMC5735852. 16: Yamasaki T, Fujinaga M, Shimoda Y, Mori W, Zhang Y, Wakizaka H, Ogawa M, Zhang MR. Radiosynthesis and evaluation of new PET ligands for peripheral cannabinoid receptor type 1 imaging. Bioorg Med Chem Lett. 2017 Sep 1;27(17):4114-4117. doi: 10.1016/j.bmcl.2017.07.040. Epub 2017 Jul 18. PMID: 28757061. 17: Khurana L, Fu BQ, Duddupudi AL, Liao YH, Immadi SS, Kendall DA, Lu D. Pyrimidinyl Biphenylureas: Identification of New Lead Compounds as Allosteric Modulators of the Cannabinoid Receptor CB1. J Med Chem. 2017 Feb 9;60(3):1089-1104. doi: 10.1021/acs.jmedchem.6b01448. Epub 2017 Jan 19. PMID: 28059509; PMCID: PMC5724760. 18: Laprairie RB, Kulkarni AR, Kulkarni PM, Hurst DP, Lynch D, Reggio PH, Janero DR, Pertwee RG, Stevenson LA, Kelly ME, Denovan-Wright EM, Thakur GA. Mapping Cannabinoid 1 Receptor Allosteric Site(s): Critical Molecular Determinant and Signaling Profile of GAT100, a Novel, Potent, and Irreversibly Binding Probe. ACS Chem Neurosci. 2016 Jun 15;7(6):776-98. doi: 10.1021/acschemneuro.6b00041. Epub 2016 Apr 25. PMID: 27046127; PMCID: PMC5358098. 19: Kulkarni PM, Kulkarni AR, Korde A, Tichkule RB, Laprairie RB, Denovan-Wright EM, Zhou H, Janero DR, Zvonok N, Makriyannis A, Cascio MG, Pertwee RG, Thakur GA. Novel Electrophilic and Photoaffinity Covalent Probes for Mapping the Cannabinoid 1 Receptor Allosteric Site(s). J Med Chem. 2016 Jan 14;59(1):44-60. doi: 10.1021/acs.jmedchem.5b01303. Epub 2015 Nov 28. PMID: 26529344; PMCID: PMC4716578. 20: Straiker A, Mitjavila J, Yin D, Gibson A, Mackie K. Aiming for allosterism: Evaluation of allosteric modulators of CB1 in a neuronal model. Pharmacol Res. 2015 Sep;99:370-6. doi: 10.1016/j.phrs.2015.07.017. Epub 2015 Jul 23. PMID: 26211948; PMCID: PMC4574285.