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. Author manuscript; available in PMC: 2015 Mar 20.
Published in final edited form as: Curr Top Med Chem. 2013;13(12):1402–1428. doi: 10.2174/1568026611313120004

Table 3.

In vitro data for inhibition of ATRA metabolism by select lead compounds that have been evaluated or developed as CYP26 inhibitors. The structures of compounds 1–13 are shown in figures 3, 4 and 5.

Compound ATRA Concentration Enzyme system IC50 Ref
Ketoconazole 50 nM [3H]ATRA for 4 hrs F9 embryonal carcinoma cells 42% inhibition of RA metablism at 1 μM [191]
100 nM 9-cisRA Recombinant CYP26A1 550 nM [27]
3 μM RA with 10 nM [11,12-3H]RA for 30 min Rat liver microsomes and rat skin homogenates 22 μM (liver)
86 μM (skin)		 [176]
80–800 μM of ATRA with 25 nCi of [15-14C]RA Hamster liver microsomes 750 nM [182]
Liarozole 100 nM ATRA MCF7 cells pretreated with ATRA 1 μM [66]
[11,12-3H (N)]ATRA for 90 min Rat Dunning R3327G prostate tumor homogenates 260 nM [112]
100 nM [3H]ATRA for 90 min MCF-7 cells pretreated with ATRA 0.44 μM [115]
20 nM [3H]ATRA Human endothelial and HepG2 cells 10 μM increased t1/2 of RA 3- to 12-fold [192]
10 μM ATRA Caco-2 cells pretreated with ATRA 90% inhibition of RA metabolism at 50 μM [193]
0.25 μM retinol RA accumulation in Sertoli, peritubular, and myoid cells isolated from rat testes 10 μM increased RA conc. 2.5-fold in Sertoli cells; no effect in peritubular or myoid cells [194]
7.72 pmol [11,12-3H]ATRA Hamster liver microsomes 6 μM [157]
100 nM [11,12-3H]ATRA for 9 hrs MCF-7 cells pretreated with ATRA 7 μM [116,171,172]
3 μM ATRA Rat liver microsomes 4.2 μM [155]
100 nM 9-cisRA Recombinant CYP26A1 microsomes 2 μM [27]
[11,12-3H]RA (100 μCi/ml) for 30 min Recombinant CYP26A1 microsomes 3 μM [133]
Talarazole [11,12-3H]RA (100 μCi/ml) Recombinant CYP26 microsomes 4 nM [133]
100 nM 9-cisRA Recombinant CYP26A1 5.1 nM [27]
R116010 100 nM 9-cisRA Recombinant CYP26A1 4.3 nM [27]
0.1 μM [11, 12-3H]RA T47D cells pretreated with 1μM ATRA for 16 hrs 8.7 nM [142]
10 nM ATRA with 0.1 μCi [11,12-3H]ATRA Microsomes from MCF-7 cells pretreated with ATRA 10 nM [167,168]
1a 7.7 pmol [11,12-3H]ATRA Hamster liver microsomes 2.3 nM
1 nM [11,12-3H]ATRA for 5 hrs MCF-7 and T47D cells pretreated with 1 μM ATRA 12–15 hrs 10.9 nM (MCF-7)
6.3 nM (T47D)		 [157]
20 μCi/ml [11,12-3H]ATRA T47D microsomes pretreated with 2.4 nM
for 30 min ATRA
0.1 or 0.8 μM [11,12-3H]ATRA LNCaP microsomes pretreated with 1 μM ATRA for 24 hrs 6.5 nM [159]
1b 7.7 pmol [11,12-3H]ATRA Hamster liver microsomes 9 pM [157]
1 nM [11,12-3H]ATRA for 5 hrs MCF-7 and T47D cells pretreated with 1 μM ATRA 12–15 hrs 200 nM (MCF-7)
215 nM (T47D)
20 μCi/ml [11,12-3H]ATRA for 30 min T47D microsomes pretreated with ATRA 40 nM
2 7.7 pmol [11,12-3H]ATRA Hamster liver microsomes 0.05 nM [157]
1 nM [11,12-3H]ATRA for 5 hrs MCF-7 and T47D cells pretreated with 1 μM ATRA 12–15 hrs 24.7 nM (MCF-7)
10 nM (T47D)
20 μCi/ml [11,12-3H]ATRA for 30 min T47D microsomes pretreated with ATRA 5.2 nM
0.1 or 0.8 μM [11,12-3H]ATRA LNCaP microsomes pretreated with 1μM ATRA for 24 hrs 90 nM [159]
3 7.7 pmol [11,12-3H]ATRA Hamster liver microsomes 43.7 nM
1 nM [11,12-3H]ATRA for 5hrs MCF-7 and T47D cells pretreated with 1 μM ATRA 12–15 hrs 56 nM (MCF-7)
24 nM (T47D)		 [157]
0.1 or 0.8 μM [11,12-3H]ATRA LNCaP microsomes pretreated with 1μM ATRA for 24 hrs 62.5 nM [159]
4 7.7 pmol [11,12-3H]ATRA Hamster liver microsomes 76.7 nM [157]
0.1 or 0.8 μM [11,12−3H]ATRA LNCaP microsomes pretreated with 1μM ATRA for 24 hrs 90 nM [159]
5 40 nM [3H]ATRA for 30 min Microsomes from T47D cells pretreated with ATRA 20 nM [169]
6 100 nM ATRA with 0.1 μCi [11,12-3H]ATRA for 9 hrs MCF-7 cells pretreated with ATRA 5 μM [172]
7 100 nM ATRA with 0.1 μCi [11,12-3H]ATRA for 24 hrs MCF-7 cells pretreated with ATRA 900 nM [172]
8 10 nM [11,12-3H]ATRA for 9 hrs MCF-7 microsomes pretreated with ATRA 500 nM [173]
Imidazole of compound 9 10 nM [11,12-3H]ATRA for 9 hrs MCF-7 microsomes pretreated with ATRA 3 nM [167]
9 100 nM [11,12-3H]ATRA for 9 hrs MCF-7 microsomes pretreated with ATRA 0.35 nM [168]
10 0.05 μCi [3H]ATRA for 3 hrs HeLa cells pretreated with ATRA 14 nM [175]
11 3 μM RA with 10 nM [11,12-3H]RA for 30 min Rat liver microsomes and rat skin homogenates 99 μM (liver)
212 μM (skin)		 [176]
12 10 nM [11,12-3H]RA for 30 min Rat liver microsomes and rat skin homogenates; fibroblast and HaCat cells pretreated with ATRA 12.8 – 19 μM [177]
13 3 μM ATRA and 10 nM [11,12-3H]ATRA for 30 min Rat liver microsomes 400 nM [116]
100 nM ATRA and 0.1 μCi [11,12-3H]ATRA for 9 hrs MCF-7 cells pretreated with ATRA 5 μM