PCS1055 dihydrochloride 

PCS1055 dihydrochloride is a potent, selective and competitive muscarinic M4 receptor antagonist with an IC₅₀ of 18.1 nM and a K_d of 5.72 nM. PCS1055 dihydrochloride inhibits radioligand [³H]-NMS binding to the M4 receptor with a K_i of 6.5 nM. PCS1055 dihydrochloride exhibits >100-fold selectivity over M1-, M3-, and M5-receptors and 30-fold selectivity at the M2 receptor. PCS1055 dihydrochloride is also a potent AChE inhibitor with IC₅₀ s of 22 nM and 120 nM for electric eel and human AChE, respectively^[1][2].

IC50: 18.1 nM (Muscarinic M4 receptor); Kd: 5.72 nM (Muscarinic M4 receptor)^[1];
IC50: 22 nM (Electric eel AChE) and 120 nM (Human AChE)^[2]

PCS1055 also antagonized functional signal transduction as demonstrates by the inhibition of agonist-stimulated GTP-γ-[³⁵S] binding. PCS1055 inhibits G protein activation in a concentration dependent manner, with the highest potency at the M4 receptors. Both studies shows that PCS1055 is most potent at the M4 receptor subtype with a binding preference of 130-, 31.2-, 426- and >1000-fold, and functional preference of 255-, 69.1-, 342- and >1000-fold over the M1-, M2-, M3- and M5 receptors, respectively^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

PCS1055 (30 mg/kg; intraperitoneal injection; male mice) treatment shows the maximal plasma levels at the 30 min time-point with 45100 nM total and 631nM unbound plasma concentrations. The maximal compound exposure observed in the brain is 11.8 nM at 1 h^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

485.49

C₂₇H₃₄Cl₂N₄

361979-40-0

[H]Cl.[H]Cl.C12=NN=C(NCCC3CCN(CC4=CC=CC=C4)CC3)C=C1CCCC5=CC=CC=C52

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Croy CH, et al. Characterization of PCS1055, a novel muscarinic M4 receptor antagonist. Eur J Pharmacol. 2016 Jul 5;782:70-6.  [Content Brief]

  [2]. Contreras JM, et al. Design, synthesis, and structure-activity relationships of a series of 3-[2-(1-benzylpiperidin-4-yl)ethylamino]pyridazine derivatives as acetylcholinesterase inhibitors. J Med Chem. 2001 Aug 16;44(17):2707-18.  [Content Brief]