Target Validation Information
TTD ID	T84634
Target Name	Cytochrome P450 26 (CYP26A1)
Type of Target	Clinical trial
Drug Potency against Target	Rambazole	Drug Info	IC50 = 4 nM
	4-((+/-)-(1H-imidazol-1-yl)-(E)-methylretinoate	Drug Info	IC50 = 40 nM	[1]
	4-((+/-)-(1H-imidazol-1-yl)-(E)-retinoic acid	Drug Info	IC50 = 2.4 nM	[1]
	LIAROZOLE	Drug Info	IC50 = 7000 nM	[2]
	Rambazole	Drug Info	IC50 = 5 nM	[2]
Action against Disease Model	Rambazole	Drug Info	Talarozole (R115866), a selective inhibitor of P450-mediated all-trans retinoic acid for the treatment of psoriasis and acne. Silencing of the CYP26B1 gene expression or reduction of CYP26B1 enzymatic activity by using siRNA or the inhibitor R115866, respectively, increased atRA-mediated signaling and resulted in decreased cell proliferation. The CYP26 inhibitor also inducedexpression of atRA-responsive genes. Therefore, atRA-induced CYP26 expression accelerated atRA inactivation in AOSMCs, giving rise to an atRA-CYP26 feedback loop. Inhibition of this loop with a CYP26inhibitor increased retinoid signaling.	[3]
References
REF 1	Novel retinoic acid metabolism blocking agents endowed with multiple biological activities are efficient growth inhibitors of human breast and pros... J Med Chem. 2004 Dec 30;47(27):6716-29.
REF 2	Novel azolyl-(phenylmethyl)]aryl/heteroarylamines: potent CYP26 inhibitors and enhancers of all-trans retinoic acid activity in neuroblastoma cells. Bioorg Med Chem. 2008 Sep 1;16(17):8301-13.
REF 3	CYP26B1 plays a major role in the regulation of all-trans-retinoic acid metabolism and signaling in human aortic smooth muscle cells. J Vasc Res. 2011;48(1):23-30.

If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.