VU0467154 (VU-0467154) is a novel and potent M4 PAM (positive allosteric modulator) with the potential to be used as a novel approach for the treatment of psychotic symptoms associated with schizophrenia and other neuropsychiatric disorders. Acting on muscarinic acetylcholine receptor (mAChR). VU0467154 exhibits robust APD-like and cognitive enhancing activity in rodents. Selective M4 PAMs could provide a therapeutic strategy for the treatment of HD.

Physicochemical Properties

Molecular Formula	C17H15F3N4O3S2
Molecular Weight	444.451211214066
Exact Mass	444.054
CAS #	1451993-15-9
Related CAS #	1451993-15-9;
PubChem CID	73774630
Appearance	Light yellow to yellow solid powder
LogP	5.166
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	10
Rotatable Bond Count	4
Heavy Atom Count	29
Complexity	708
Defined Atom Stereocenter Count	0
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)
Chemical Name	5-amino-3,4-dimethyl-N-[[4-(trifluoromethylsulfonyl)phenyl]methyl]thieno[2,3-c]pyridazine-6-carboxamide
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	VU0467154 is a muscarinic acetylcholine receptor (mAChR) positive allosteric modulator that has pEC50s of 7.75, 6.2, and 6.2 for rat, human, and cynomolgus monkey (cyno) M4 receptors, respectively. It can greatly increase the responsiveness to ACh. 6. In rats and humans, VU0467154 did not increase ACh responses in M1, M2, M3, or M5 [1].
ln Vivo	Rats' amphetamine-induced hyperlocomotion is reversed by VU0467154 (1–56.6 mg/kg, oral or intraperitoneal injection). In wild-type mice, VU0467154 (0.3-30 mg/kg, ip) reverses the hyperlocomotion caused by amphetamine and MK-801, but not in M4 KO mice. In wild-type mice, VU0467154 alone also improves the learning of context- and cue-mediated fear conditioning [1].
References	[1]. 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.

Solubility Data

Solubility (In Vitro)

DMSO : ~13.89 mg/mL (~31.25 mM)

Solubility (In Vivo)

Solubility in Formulation 1: 1.39 mg/mL (3.13 mM) in 10% DMSO + 40% PEG300 +5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 13.9 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 + to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.2500 mL	11.2499 mL	22.4997 mL
	5 mM	0.4500 mL	2.2500 mL	4.4999 mL
	10 mM	0.2250 mL	1.1250 mL	2.2500 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.