VU0467154 | CAS#1451993-15-9 | M4 Postive Allosteric Modulator

MedKoo Cat#: 530355 | Name: VU0467154

Description:

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

VU0467154 is a potent and selective M4 PAM. VU0467154 exhibits robust APD-like and cognitive enhancing activity in rodents. Selective M4 PAMs could provide a therapeutic strategy for the treatment of HD. VU154 has efficacy on anxiety, social preference, cognitive, and respiratory phenotypes in Mecp2+/- mice; however, the therapeutic range is narrow, with benefits seen at 3 mg/kg concentrations, but not 1 or 10 mg/kg.

Chemical Structure

VU0467154

CAS#1451993-15-9

Theoretical Analysis

MedKoo Cat#: 530355

Name: VU0467154

CAS#: 1451993-15-9

Chemical Formula: C17H15F3N4O3S2

Exact Mass: 444.0538

Molecular Weight: 444.45

Elemental Analysis: C, 45.94; H, 3.40; F, 12.82; N, 12.61; O, 10.80; S, 14.43

Price and Availability

Size	Price	Availability
10mg	USD 150.00	Ready to ship
25mg	USD 250.00	Ready to ship
50mg	USD 450.00	Ready to ship
100mg	USD 850.00	Ready to ship
200mg	USD 1,450.00	Ready to ship
500mg	USD 3,250.00	Ready to ship

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Related CAS #

1451993-15-9

Synonym

VU0467154, VU-0467154, VU 0467154; VU154; VU-154; VU 154;

IUPAC/Chemical Name

5-Amino-3,4-dimethyl-N-[[4-[(trifluoromethyl)sulfonyl]phenyl]methyl]thieno[2,3-c]pyridazine-6-carboxamide

InChi Key

UDSFKIFLJPECRN-UHFFFAOYSA-N

InChi Code

InChI=1S/C17H15F3N4O3S2/c1-8-9(2)23-24-16-12(8)13(21)14(28-16)15(25)22-7-10-3-5-11(6-4-10)29(26,27)17(18,19)20/h3-6H,7,21H2,1-2H3,(H,22,25)

SMILES Code

O=C(C1=C(N)C2=C(C)C(C)=NN=C2S1)NCC3=CC=C(S(=O)(C(F)(F)F)=O)C=C3

Appearance

Yellow 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

Certificate of Analysis

View CoA: current batch, Lot# S8S05C14

QC Data

View QC data: current batch, Lot#S8S05C14

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Preparing Stock Solutions

The following data is based on the product molecular weight 444.45 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

1: Cikowski J, Holt C, Arthur B, Smith M, Gonzalez S, Lindsley CW, Niswender CM, Gogliotti RG. Optimized Administration of the M4 PAM VU0467154 Demonstrates Broad Efficacy, but Limited Effective Concentrations in Mecp2+/- Mice. ACS Chem Neurosci. 2022 Jul 6;13(13):1891-1901. doi: 10.1021/acschemneuro.2c00113. Epub 2022 Jun 7. PMID: 35671352; PMCID: PMC9266622. 2: Walker LC, Huckstep KL, Chen NA, Hand LJ, Lindsley CW, Langmead CJ, Lawrence AJ. Muscarinic M4 and M5 receptors in the ventral subiculum differentially modulate alcohol seeking versus consumption in male alcohol-preferring rats. Br J Pharmacol. 2021 Sep;178(18):3730-3746. doi: 10.1111/bph.15513. Epub 2021 Jun 3. PMID: 33942300. 3: Walker LC, Berizzi AE, Chen NA, Rueda P, Perreau VM, Huckstep K, Srisontiyakul J, Govitrapong P, Xiaojian J, Lindsley CW, Jones CK, Riddy DM, Christopoulos A, Langmead CJ, Lawrence AJ. Acetylcholine Muscarinic M4 Receptors as a Therapeutic Target for Alcohol Use Disorder: Converging Evidence From Humans and Rodents. Biol Psychiatry. 2020 Dec 15;88(12):898-909. doi: 10.1016/j.biopsych.2020.02.019. Epub 2020 Feb 29. PMID: 32331824. 4: Gould RW, Grannan MD, Gunter BW, Ball J, Bubser M, Bridges TM, Wess J, Wood MW, Brandon NJ, Duggan ME, Niswender CM, Lindsley CW, Conn PJ, Jones CK. Cognitive enhancement and antipsychotic-like activity following repeated dosing with the selective M4 PAM VU0467154. Neuropharmacology. 2018 Jan;128:492-502. doi: 10.1016/j.neuropharm.2017.07.013. Epub 2017 Jul 17. PMID: 28729220; PMCID: PMC6756753. 5: Dall C, Weikop P, Dencker D, Molander AC, Wörtwein G, Conn PJ, Fink-Jensen A, Thomsen M. Muscarinic receptor M4 positive allosteric modulators attenuate central effects of cocaine. Drug Alcohol Depend. 2017 Jul 1;176:154-161. doi: 10.1016/j.drugalcdep.2017.03.014. Epub 2017 May 16. PMID: 28544993; PMCID: PMC6423356. 6: Melancon BJ, Wood MR, Noetzel MJ, Nance KD, Engelberg EM, Han C, Lamsal A, Chang S, Cho HP, Byers FW, Bubser M, Jones CK, Niswender CM, Wood MW, Engers DW, Wu D, Brandon NJ, Duggan ME, Conn PJ, Bridges TM, Lindsley CW. Optimization of M4 positive allosteric modulators (PAMs): The discovery of VU0476406, a non-human primate in vivo tool compound for translational pharmacology. Bioorg Med Chem Lett. 2017 Jun 1;27(11):2296-2301. doi: 10.1016/j.bmcl.2017.04.043. Epub 2017 Apr 13. PMID: 28442253; PMCID: PMC5508548. 7: Wood MR, Noetzel MJ, Poslusney MS, Melancon BJ, Tarr JC, Lamsal A, Chang S, Luscombe VB, Weiner RL, Cho HP, Bubser M, Jones CK, Niswender CM, Wood MW, Engers DW, Brandon NJ, Duggan ME, Conn PJ, Bridges TM, Lindsley CW. Challenges in the development of an M4 PAM in vivo tool compound: The discovery of VU0467154 and unexpected DMPK profiles of close analogs. Bioorg Med Chem Lett. 2017 Jan 15;27(2):171-175. doi: 10.1016/j.bmcl.2016.11.086. Epub 2016 Nov 30. PMID: 27939174; PMCID: PMC5340297. 8: Foster DJ, Wilson JM, Remke DH, Mahmood MS, Uddin MJ, Wess J, Patel S, Marnett LJ, Niswender CM, Jones CK, Xiang Z, Lindsley CW, Rook JM, Conn PJ. Antipsychotic-like Effects of M4 Positive Allosteric Modulators Are Mediated by CB2 Receptor-Dependent Inhibition of Dopamine Release. Neuron. 2016 Sep 21;91(6):1244-1252. doi: 10.1016/j.neuron.2016.08.017. Epub 2016 Sep 8. PMID: 27618677; PMCID: PMC5033724. 9: Gould RW, Nedelcovych MT, Gong X, Tsai E, Bubser M, Bridges TM, Wood MR, Duggan ME, Brandon NJ, Dunlop J, Wood MW, Ivarsson M, Noetzel MJ, Daniels JS, Niswender CM, Lindsley CW, Conn PJ, Jones CK. State-dependent alterations in sleep/wake architecture elicited by the M4 PAM VU0467154 - Relation to antipsychotic-like drug effects. Neuropharmacology. 2016 Mar;102:244-53. doi: 10.1016/j.neuropharm.2015.11.016. Epub 2015 Nov 23. PMID: 26617071; PMCID: PMC4809053. 10: Pancani T, Foster DJ, Moehle MS, Bichell TJ, Bradley E, Bridges TM, Klar R, Poslusney M, Rook JM, Daniels JS, Niswender CM, Jones CK, Wood MR, Bowman AB, Lindsley CW, Xiang Z, Conn PJ. Allosteric activation of M4 muscarinic receptors improve behavioral and physiological alterations in early symptomatic YAC128 mice. Proc Natl Acad Sci U S A. 2015 Nov 10;112(45):14078-83. doi: 10.1073/pnas.1512812112. Epub 2015 Oct 27. PMID: 26508634; PMCID: PMC4653197. 11: Bubser M, Bridges TM, Dencker D, Gould RW, Grannan M, Noetzel MJ, Lamsal A, Niswender CM, Daniels JS, Poslusney MS, Melancon BJ, Tarr JC, Byers FW, Wess J, Duggan ME, Dunlop J, Wood MW, Brandon NJ, Wood MR, Lindsley CW, Conn PJ, Jones CK. Selective activation of M4 muscarinic acetylcholine receptors reverses MK-801-induced behavioral impairments and enhances associative learning in rodents. ACS Chem Neurosci. 2014 Oct 15;5(10):920-42. doi: 10.1021/cn500128b. Epub 2014 Aug 19. PMID: 25137629; PMCID: PMC4324418.