Pyridoclax(MR29072)

Cas No.:	1651890-44-6
Chemical Name:	(E)-3'-methyl-3''-styryl-3,2':5',2'':5'',3'''-quaterpyridine
Synonyms:	MR-29072,MR 29072
SMILES:	CC1=C(N=CC(=C1)C2=C(C=C(C=N2)C3=CN=CC=C3)/C=C/C4=CC=CC=C4)C5=CN=CC=C5
Formula:	C29H22N4
M.Wt:	426.51
Purity:	>98%
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Description:	Pyridoclax is a potential Mcl-1 inhibitor.
Target:	Mcl-1
In Vitro:	Pyridoclax directly binds to Mcl-1. Without cytotoxic activity when administered as a single agent, Pyridoclax induces apoptosis in combination with Bcl-xL-targeting siRNA or with ABT-737 in ovarian, lung, and mesothelioma cancer cells[1]. Pyridoclax directly binds to Mcl-1, and hence sensitizes ovarian carcinoma cells to Bcl-xL-targeting strategies. Pyridoclax induces apoptosis in ovarian, and also in lung, and mesothelioma cancer cells when it is administrated in combination with Bcl-xL-targeting siRNA or Bcl-xL targeting molecules such as ABT-737 or its orally available derivative ABT-263[2].
Kinase Assay:	For donor saturating assays, Hela cells are seeded on 12-well plates and transfected with 200 ng/well of plasmid pRluc-BimL coding for BRET donor and an increasing quantity of BRET acceptor plasmids peYFP-Mcl-1 (or with pCMV-Mcl-1 as a control). Twenty-four hours after transfection, cells are trypsinized, reseeded into white flat bottom 96-well plates, and incubated for another day before measurements. A single donor/acceptor ratio (200/800) is used to carry out the drug treatment assay. After reseeding, cells are then subject to a 16 h Pyridoclax treatment. Light emission at 485 and 530 nm is measured consecutively using the Mithras fluorescence-luminescence detector LB 940 after adding the luciferase substrate, coelenterazine H, at a final concentration of 5 μM. BRET ratios are calculated[1].
References:	[1]. Gloaguen C, et al. First evidence that oligopyridines, α-helix foldamers, inhibit Mcl-1 and sensitize ovarian carcinoma cells to Bcl-xL-targeting strategies. J Med Chem. 2015 Feb 26;58(4):1644-68. [2]. Groo AC, et al. Comparison of 2 strategies to enhance Pyridoclax solubility: Nanoemulsion delivery system versus salt synthesis. Eur J Pharm Sci. 2017 Jan 15;97:218-226.