Table 3.

Summary of New AROM Inhibitors Since 2009

compd	type	name	IC50	assayed against, assay type	exptl binding mode verification
1–9	C6-substituted 2-alkynyloxy compounds46	C6-substituted androsta-1,4-diene-3,17-dione	20–18100 nM	Purified AROM and MCF- 7a,a 3H2O, antiproliferation	Yes: X-ray
10	A- and D-ring ASD derivative111	3β-Hydroxyandrost-4-en-17-one	0.18 μM	PMTW	No
11	A- and D-ring ASD derivative111	Androst-4-en-17-one	0.14 μM	PMTW	No
12	A- and D-ring ASD derivative111	4α,5α-Epoxyandrostan-17-one	0.97 μM	PMTW	No
13	A- and D-ring ASD derivative111	5α-Androst-3-en-17-one	0.23 μM	PMTW	No
14	A- and D-ring ASD derivative111	3α,4α-Epoxy-5α-androstan-17-one	0.15 μM	PMTW	No
15	A- and D-ring ASD derivative111	5α-Androst-2-en-17-one	1.7 μM	PMTW	No
16	A- and D-ring ASD derivative111	2α,3α-Epoxy-5α-androstan-17-one	1.2 μM	PMTW	No
17	7α-allylandrostanes112	7α-Allylandrost-4-ene-3,17-dione	0.59 μM	Placental microsomes, 3H2O (PMTW)b,c	No
18	7α-allylandrostane112	7α-Allylandrost-4-en-17-one	0.75 μM	PMTW	No
19	7α-allylandrostane112	7α-Allyl-3-oxoandrosta-1,4-dien-17β-ol	0.45 μM	PMTW	No
20	7α-allylandrostane112	7α-Allylandrosta-1,4-diene-3,17-dione	0.47 μM	PMTW	No
21	NCIe compound (B-nor-androstenedione scaffold)139	3a,5b,10-Trimethyl-1,2,4,5,5a,6,7,10,10a,10b-decahydrocyclopenta[a]fluorene-3,8-dione	0.27 μM	PMTW	No
23	Imidazolyl substituted steroidal derivative113	16β-(Imidazol-1-yl)-4-androstene-3,17-dione	0.18 μM	PMTW	No
24	Imidazolyl substituted steroidal derivative113	16β-(Imidazol-1-yl)androsta-1,4-diene-3,17-dione	0.168 μM	PMTW	No
25	Androstane114	17β-Hydroxy-4-oxo-5α-androstano[2,3-d]pyrazole	512.0 nM	PMTW	No: MDd
26	Androstane114	2-Cyano-3,17β-dihydroxy-5α-androst-2-en-4-one	1019.8 nM	PMTW	No: MD
27	Carbonitrile115	16 β-Cyano-17 β-hydroxy-4-phenylthia-4-androsten-3-one	169.3 nM	PMTW	No: MD
Nonsteroidal AROM Inhibitors
22	NCIe compound NSC613604139	5-(4-Chloroanilino)-2-methyl-9-nitro-5H-chromeno[4,3-b] pyridine-3-carbonitrile	0.67 μM	PMTW	No
28	Quinoline derivative-dual CYP11B2/CYP19 inhibitor119	8-[(3-Methylphenyl)(pyridin-4-yl)methyl]-1,2,5,6-tetrahydro- 4H-pyrrolo[3,2,1-ij]quinolin-4-one	32 nM	PMTW	No: MD
29	Azolylmethylpyrroloquinoline120	4-((1H-Imidazol-1-yl)methyl)-7-ethyl-2-phenyl-7H-pyrrolo[2,3- h]quinoline	5.3 nM	Supersomesg/H295R cells, FCAh/antiproliferation	No: MD
30	Azolylmethylpyrroloquinoline120	4-((1H-1,2,4-Triazol-1-yl)methyl)-2-(4-methoxyphenyl)-7H- pyrrolo [2,3-h]quinoline	>10000 nM	Supersomes/H295R cells, FCA/antiproliferation	No: MD
31	Azolylmethylpyrroloquinoline120	9-((1H-Imidazol-1-yl)methyl)-3-ethyl-7-phenyl-3H-pyrrolo- [3,2-f ]quinoline	3.1 nM	Supersomes/H295R cells, FCA/antiproliferation	No: MD
32	Azolylmethylpyrroloquinoline120	9-((1H-1,2,4-Triazol-1-yl)methyl)-3-ethyl-7-phenyl-3H-pyrrolo [3,2-f ]quinoline	13.3 nM	Supersomes/H295R cells, FCA/antiproliferation	No: MD
33	NNCf compound (imidazolyl quinoline)121	2-(4-Fluorophenyl)-4-(imidazol-1-yl)quinoline	0.8 μM	Supersomes/T47cells, E2 ELISA/antiproliferation	No: MD
34	Isoflavanone derivative122	3-(4-Phenoxyphenyl)chroman-4-one	2.4 μM	Supersomes/FCA	No: MD
35	Isoflavanone derivative122	6-Methoxy-3-phenylchroman-4-one	0.3 μM	Supersomes/FCA	No: MD
36	Isoflavanone derivative122	3-(Pyridin-3-yl)chroman-4-one	5.8 μM	Supersomes/FCA	No: MD
37	Flavans123	5-Methoxy-8-formyl-4,7-dihydroxyflavan	40 nM	Supersomes/FCA	No: MD
38	4,7-disubstituted coumarin124	7-(3,4-Difluorophenoxy)-4-(1H-imidazol-1-ylmethyl)-2H- chromen-2-one	47 nM	PMTW	No: MD
39	4,7- disubstituted coumarin124	4-(1H-Imidazol-1-ylmethyl)-7-phenoxy-2H-chromen-2-one	150 nM	PMTW	No: MD
40	Dual AROM/STS inhibitor126	4-{[(4-Cyanophenyl)(1H-imidazol-1-yl)amino]methyl}-3- fluorophenyl sulfamate	0.2 nM	JEG3 cells, 3H2Oc	No: MD
41	Dual AROM/STS inhibitor130	2-Bromo-4-(2-(4-cyanophenyl)-2-(1H-1,2,4-triazol-1-yl)ethyl) phenyl sulfamate	0.9 nM	JEG3 cells, 3H2Oc	No
42	Dual AROM/STS inhibitor129	5′-((1H-1,2,4-Triazol-1-yl)methyl)-2′-cyanobiphenyl-4-yl sulfamate	2 nM	JEG3 cells, 3H2Oc	No
43	Dual AROM/STS inhibitor 129	5′-((1H-1,2,4-Triazol-1-yl)methyl)-3-chloro-2′-cyanobiphenyl- 4-yl sulfamate	0.5 nM	JEG3 cells, 3H2Oc	No
44	Dual AROM/STS inhibitor 128	2-Chloro-4-(((6-cyanobiphenyl-3-yl)(4H-1,2,4-triazol-4-yl) amino)methyl)phenyl sulfamate	15 pM	JEG3 cells, 3H2Oc	No: MD
45	Dual AROM/STS inhibitor128	2-Bromo-4-(((6-cyanobiphenyl-3-yl)(4H-1,2,4-triazol-4-yl) amino)methyl)phenyl sulfamate	18 pM	JEG3 cells, 3H2Oc	No: MD
46	Tamoxifen metabolite131	Z-4-Hydroxytamoxifen	530 μM	Supersomes/T to E2i	No: MD
47	Tamoxifen metabolite131	Z-Norendoxifen	30 nM	Supersomes/T to E2	No: MD
48	Tamoxifen metabolite131	Z-Endoxifen	6 μM	Supersomes/T to E2	No: MD
49	Tamoxifen metabolite132	(Z)-Norendoxifen	1029 nM	Supersomes/FCA	No: MD
50	Tamoxifen metabolite132	(E)-Norendoxifen	77 nM	Supersomes/FCA	No: MD
51	Tamoxifen metabolite132	(E,Z)-Norendoxifen	102 nM	Supersomes/FCA	No: MD
52	Sulfonamide derivative133	7-((1-(3-((6,7-Dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl) sulfonyl)phenyl)-1H-1,2,3-triazol-4-yl)methoxy)-2H-chromen-2-one	0.2 μM	Supersomes/T to E2	No: MD
53	ASINEX compounds (sulfonamide derivative)138	1-(3-tert-Butyl-4-methoxybenzenesulfonyl)-3-(imidazol-1ylmethyl)piperdine	9.4 nM	Supersomes/FCA	No: MD
54	ASINEX compounds (sulfonamide derivative)138	N-[3-(Imidazol-1-yl)propyl]-2,3-dihydro-1,4-benzodioxine-6-sulfonamide	119 nM	Supersomes/FCA	No: MD
55	Aryl halide134	2-[7-Bromo-1-(3-ethoxypropyl)imidazo[4,5-c] pyridin-5-ium-5-yl]-1-phenylethanone	20 nM	Supersomes/FCA	No: MD
56	Indole–imidazole derivative135	2-(Imidazol-1-ylmethyl)-1-[4-(trifluoromethyl)phenyl]indole	4.9 nM	Placental microsomes, ELISA	No
57	Casimiroin analogue136	N-Methylated casimiroin analogues: 5,6,8-trimethoxy-1,4-dimethylquinolin-2(1H)-one	0.1 μM	Supersomes/FCA	No: MD
58	Casimiroin analogue136	Non-N-methylated casimiroin analogues: 6-methyl[1,3]dioxolo [4,5-h]quinolin-8(9H)-one	>98.5 μM	Supersomes/FCA	No: MD
59	Casimiroin analogue136	Casimiroin	3.9 μM	Supersomes/FCA	No: MD
60	Xanthone scaffold137	4-Imidazol-1-ylmethylthioxanthen-9-one	4 nM	PMTW	No
61	Xanthone scaffold137	1-(4-Nitro-2-phenylsulfanylbenzyl)-1H-imidazole	5.6 nM	PMTW	No
62	ASINEX compounds (morpholinoethanone derivative)138	1-[2-(Imidazol-1-ylmethyl)morpholin-4-yl]-2-(3,4,5-trimethoxyphenyl)ethanone	59.2 nM	Supersomes/FCA	No: MD
63	ASINEX compounds (imdazolylacetamide)138	N-[2-(4-Fluorophenoxy)phenyl]-2-(imidazol-1-yl)acetamide	248 nM	Supersomes/FCA	No: MD

^aMCF-7a: a MCF-7 cell line stably expressing AROM as described.⁵⁹

^bPMTW: placental microsomes, tritiated water assay.

^c3H₂O: tritiated water.

^dMD: molecular docking.

^eNCI: National Cancer Institute.

^fNNC: National Nanjing Center for Drug Screening.

^gSupersomes: commerical mixture of baculovirus AROM microsomes and reductase.

^hFCA: fluorescent CYP19 inhibition assay, which measures the conversion of a fluorescence substrate to its metabolite, a hydroxylation reaction.

ⁱT to E2 assay, which measures T to E2 conversion by HPLC.