Pregnenolone 16«-carbonitrile

A.H. Conney (1972). Pregnenolone-16-carbonitrile A new type of inducer of drug-metabolizing enzymes. Arch. Biochem. Biophys. 152, 457 62. 

Figure 13.2 Schematic representation of the creation of hPXR humanized mice. The humanization was achieved in the liver only when the liver-specific albumin promoter was used to direct the transgene expression, or in both the liver and the intestine when the fatty acid binding protein promoter was used. PCN, pregnenolone-16a-carbonitrile RIF, rifampicin. + and mean induction and lack of induction, respectively.

Chen, C., Staudinger, J.L. and Klaassen, C.D. (2003) Nuclear receptor, pregnane X receptor, is required for induction of UDP-glucuronosyltransferases in mouse liver by pregnenolone-16 alpha-carbonitrile. Drug Metabolism and Disposition, 31, 908—915. 

Abbreviations Pb, phenobarbital PCN, pregnenolone-16 a-carbonitrile 3MC, 3-methylcholanthrene Aro, arochlor 1254. Sourcer. From Ref. 38. 

Rifampicin and pregnenolone-16a-carbonitrile (PCN) induce members of the CYP3A family and represent a third type of inducer, in that the substrate specificity of the microsomes from treated animals differs from that of the microsomes from either phenobarbital-treated or TCDD-treated animals. Inducing substrates of this class include endogenous and synthetic glucocorticoids (e.g., dexamethasone), pregnane... 

Liu S, Tam D, Chen X, et al. P-glycoprotein and an unstirred water layer barring digoxin absorption in the vascularly perfused rat small intestine preparation induction studies with pregnenolone-16alpha-carbonitrile. Drug Metab Dispos 2006 34 1468-1479. 

P450 IIIA4 Human nf Pregnenolone, 16a-carbonitrile Ethinylestradiol Nifedipine N-oxidase... 

Marek, C.J., Tucker, S.J., Konstantinou, D.K., Elrick, L.J., Haefner, D., Sigalas, C., Murray, G.I., Goodwin, B. and Wright, M.C. (2005) Pregnenolone-16a-carbonitrile inhibits rodent liver fibrogenesis via PXR (pregnane X receptorj-dependent and PXR-independent mechanisms. The Biochemical Journal, 387, 601—608. 

Pb phenobarbital PCN pregnenolone-16a-carbonitrile 3MC 3-methylcholanthrene Aro arochlor 1254. Data from Powis et al. (1977) In Microsomes and Drug Oxidations, edited by V.Ullrich, A.Roots, A.Hildebrandt, R.W. Estabrook and A.H.Conney, p. 137 (Oxford Pergamon Press). 

Carbamazepine, dexamethasone, glutethimide, nevirapine, phenobarbital, phenytoin, pregnenolone-16a-carbonitrile, progesterone, rifabutin, rifampin, ritonavir, St. John s Wort, sulfadimidine, sulfinpyrazone, troglitazone, troleandomycin... 

Burger, H. J., Schuetz, J. D., Schuetz, E. G., and Guzelian, P. S. (1992) Paradoxical transcriptional activation of rat liver cytochrome P-450 3A1 by dexamethasone and the antiglucocorticoid pregnenolone 16 alpha-carbonitrile analysis by transient transfection into primary monolayer cultures of adult rat hepatocytes. Proc. Natl Acad. Sci. USA 89, 2145-2149. 

---