Proadifen

Proadifen

Names
IUPAC name 2-Diethylaminoethyl 2,2-diphenylpentanoate
Other names SKF 525-A
Identifiers
CAS Number	302-33-0
ChEMBL	ChEMBL282567
ChemSpider	4741
Jmol interactive 3D	Image
PubChem	4910
UNII	A510CA4CBT
InChI InChI=1S/C23H31NO2/c1-4-17-23(20-13-9-7-10-14-20,21-15-11-8-12-16-21)22(25)26-19-18-24(5-2)6-3/h7-16H,4-6,17-19H2,1-3H3
SMILES O=C(OCCN(CC)CC)C(c1ccccc1)(c2ccccc2)CCC
Properties
Chemical formula	C23H31NO2
Molar mass	353.51 g·mol^−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references

Proadifen (SKF-525A) is a non-selective inhibitor of cytochrome P450 enzymes, preventing some types of drug metabolism.^[1] It is also an inhibitor of neuronal nitric oxide synthase (NOS), CYP-dependent (cytochrome P450-dependent) arachidonate metabolism, transmembrane calcium influx, and platelet thromboxane synthesis. Further documented effects include the blockade of ATP-sensitive inward rectifier potassium channel 8 (KIR6.1), and stimulation of endothelial cell prostacyclin production.^[2]

Proadifen exerts apoptotic/anti-proliferate (tumour suppressing) effects in certain forms of cancer (HT-29 colon adenocarcinoma), believed to be caused by mediation of Glycogen synthase kinase 3 β (GSK-3β). In the same study administration of proadifen was demonstrated to produce time- and dose-dependent phosphatidylserine externalization, caspase-3 activation and PARP cleavage. Intense upregulation of NAG-1 and ATF3 and downregulation of Mcl-1 and Egr-1 were also observed.^[3]

Proadifen has been demonstrated to inhibit the nicotinic acetylcholine receptor (NAChR) and muscarinic acetylcholine receptor (MAChR) in rats.^[4]

References

1. Marshall, FN; Williamson, HE (1964). "Natruretic Response During Infusion of Beta-Diethylaminoethyl-Diphenylpropyl Acetate Hydrocloride (Skf 525-A)". The Journal of Pharmacology and Experimental Therapeutics 143: 395–400. PMID 14161153.
2. "Santa Cruz Biotech".
3. University in Košice, Slovakia; Institute of Biology and Ecology: Rastislav Jendzelovsky, Jan Koval, Jaromír Mikeš, Zuzana Jendzelovska, Jana Plsikova, and Peter Fedoročko (June 2012). "Inhibition of GSK-3β reverses the pro-apoptotic effect of proadifen (SKF-525A) in HT-29 colon adenocarcinoma cells". Toxicology In Vitro.
4. "Santa Cruz Biotech".