Target Information
Target General Information | Top | |||||
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Target ID |
T84621
(Former ID: TTDS00420)
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Target Name |
Steroid 11-beta-hydroxylase (CYP11B1)
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Synonyms |
S11BH; P450C11; P-450c11; CYPXIB1; CYP11B1
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Gene Name |
CYP11B1
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Target Type |
Successful target
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[1] | ||||
Disease | [+] 2 Target-related Diseases | + | ||||
1 | Breast cancer [ICD-11: 2C60-2C6Y] | |||||
2 | Cushing syndrome [ICD-11: 5A70] | |||||
Function |
Has steroid 11-beta-hydroxylase activity. In addition to this activity, the 18 or 19-hydroxylation of steroids and the aromatization of androstendione to estrone have also been ascribed to cytochrome P450 XIB.
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BioChemical Class |
Paired donor oxygen oxidoreductase
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UniProt ID | ||||||
EC Number |
EC 1.14.15.4
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Sequence |
MALRAKAEVCMAVPWLSLQRAQALGTRAARVPRTVLPFEAMPRRPGNRWLRLLQIWREQG
YEDLHLEVHQTFQELGPIFRYDLGGAGMVCVMLPEDVEKLQQVDSLHPHRMSLEPWVAYR QHRGHKCGVFLLNGPEWRFNRLRLNPEVLSPNAVQRFLPMVDAVARDFSQALKKKVLQNA RGSLTLDVQPSIFHYTIEASNLALFGERLGLVGHSPSSASLNFLHALEVMFKSTVQLMFM PRSLSRWTSPKVWKEHFEAWDCIFQYGDNCIQKIYQELAFSRPQQYTSIVAELLLNAELS PDAIKANSMELTAGSVDTTVFPLLMTLFELARNPNVQQALRQESLAAAASISEHPQKATT ELPLLRAALKETLRLYPVGLFLERVASSDLVLQNYHIPAGTLVRVFLYSLGRNPALFPRP ERYNPQRWLDIRGSGRNFYHVPFGFGMRQCLGRRLAEAEMLLLLHHVLKHLQVETLTQED IKMVYSFILRPSMFPLLTFRAIN Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
ADReCS ID | BADD_A06083 | |||||
HIT2.0 ID | T10HXK |
Drugs and Modes of Action | Top | |||||
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Approved Drug(s) | [+] 3 Approved Drugs | + | ||||
1 | FADROZOLE | Drug Info | Approved | Breast cancer | [2], [3], [4] | |
2 | Metyrapone | Drug Info | Approved | Cushing disease | [5], [6] | |
3 | Osilodrostat | Drug Info | Approved | Cushing disease | [7] | |
Mode of Action | [+] 2 Modes of Action | + | ||||
Inhibitor | [+] 150 Inhibitor drugs | + | ||||
1 | FADROZOLE | Drug Info | [8] | |||
2 | Metyrapone | Drug Info | [1] | |||
3 | (3-((1H-imidazol-1-yl)methyl)phenyl)methanol | Drug Info | [8] | |||
4 | (4-((1H-imidazol-1-yl)methyl)phenyl)methanol | Drug Info | [8] | |||
5 | 1-(2-Phenoxy-ethyl)-1H-imidazole | Drug Info | [9] | |||
6 | 1-(3,4-dihydronaphthalen-2-yl)-1H-imidazole | Drug Info | [10] | |||
7 | 1-(3-Bromobenzyl)-1H-imidazole | Drug Info | [8] | |||
8 | 1-(3-Chlorobenzyl)-1H-imidazole | Drug Info | [8] | |||
9 | 1-(3-Fluorobenzyl)-1H-imidazole | Drug Info | [8] | |||
10 | 1-(3-Methoxy-naphthalen-2-yl)-1H-imidazole | Drug Info | [11] | |||
11 | 1-(4-Aminobenzyl)-1H-imidazole | Drug Info | [8] | |||
12 | 1-(4-Bromobenzyl)-1H-imidazole | Drug Info | [8] | |||
13 | 1-(4-Bromobenzyl)-5-phenyl-1H-imidazole | Drug Info | [8] | |||
14 | 1-(4-Chlorobenzyl)-5-phenyl-1H-imidazole | Drug Info | [8] | |||
15 | 1-(4-Cyanobenzyl)-5-(2-fluorophenyl)-1H-imidazole | Drug Info | [8] | |||
16 | 1-(4-Cyanobenzyl)-5-(2-methylphenyl)-1H-imidazole | Drug Info | [8] | |||
17 | 1-(4-Cyanobenzyl)-5-(3-fluorophenyl)-1H-imidazole | Drug Info | [8] | |||
18 | 1-(4-Cyanobenzyl)-5-(3-methylphenyl)-1H-imidazole | Drug Info | [8] | |||
19 | 1-(4-Cyanobenzyl)-5-(4-fluorophenyl)-1H-imidazole | Drug Info | [8] | |||
20 | 1-(4-Cyanobenzyl)-5-(4-methylphenyl)-1H-imidazole | Drug Info | [8] | |||
21 | 1-(4-Cyanobenzyl)-5-(4-pyridyl)-1H-imidazole | Drug Info | [8] | |||
22 | 1-(4-Cyanobenzyl)-5-bromo-1H-imidazole | Drug Info | [8] | |||
23 | 1-(4-Cyanobenzyl)-5-formyl-1H-imidazole | Drug Info | [8] | |||
24 | 1-(4-Cyanobenzyl)-5-hydroxymethyl-1H-imidazole | Drug Info | [8] | |||
25 | 1-(4-Cyanobenzyl)-5-methyl-1H-imidazole | Drug Info | [8] | |||
26 | 1-(4-Cyanobenzyl)-5-phenyl-1H-imidazole | Drug Info | [8] | |||
27 | 1-(4-fluorobenzyl)-1H-imidazole | Drug Info | [8] | |||
28 | 1-(4-Fluorobenzyl)-5-phenyl-1H-imidazole | Drug Info | [8] | |||
29 | 1-(4-Methoxybenzyl)-5-phenyl-1H-imidazole | Drug Info | [8] | |||
30 | 1-(6-Methoxy-naphthalen-2-yl)-1H-imidazole | Drug Info | [11] | |||
31 | 1-Benzyl-5-phenyl-1H-imidazole | Drug Info | [8] | |||
32 | 1-Ethyl-3-imidazol-1-ylmethyl-1H-indole | Drug Info | [12] | |||
33 | 1-Naphthalen-2-yl-1H-imidazole | Drug Info | [11] | |||
34 | 1-Phenyl-2-pyridin-3-yl-propan-1-one | Drug Info | [13] | |||
35 | 2-Methyl-1,2-di-pyridin-3-yl-1-methoxypropane | Drug Info | [13] | |||
36 | 2-Methyl-1,2-di-pyridin-3-yl-propan-1-one oxime | Drug Info | [13] | |||
37 | 2-Methyl-1,2-di-pyridin-3-yl-propane | Drug Info | [13] | |||
38 | 2-Methyl-1,2-di-pyridin-3-yl-propylchloride | Drug Info | [13] | |||
39 | 2-Methyl-1,2-di-pyridin-3-yl-propyliodide | Drug Info | [13] | |||
40 | 2-Methyl-1-phenyl-2-pyridin-3-yl-propan-1-ol | Drug Info | [13] | |||
41 | 2-Methyl-1-phenyl-2-pyridin-3-yl-propan-1-one | Drug Info | [13] | |||
42 | 3-((1H-imidazol-1-yl)methyl)aniline | Drug Info | [8] | |||
43 | 3-(1,1-Dimethyl-2-phenyl-ethyl)-pyridine | Drug Info | [13] | |||
44 | 3-(1,2-dihydroacenaphthylen-3-yl)pyridine | Drug Info | [14] | |||
45 | 3-(1,2-dihydroacenaphthylen-5-yl)pyridine | Drug Info | [14] | |||
46 | 3-(1-Benzyl-1H-imidazol-5-yl)-1-propanol | Drug Info | [8] | |||
47 | 3-(1-Chloro-7-methoxy-naphthalen-2-yl)-pyridine | Drug Info | [11] | |||
48 | 3-(1-ethyl-3,4-dihydronaphthalen-2-yl)-pyridine | Drug Info | [10] | |||
49 | 3-(1-methyl-3,4-dihydronaphthalen-2-yl)-pyridine | Drug Info | [10] | |||
50 | 3-(1H-inden-2-yl)pyridine | Drug Info | [10] | |||
51 | 3-(2,3-Dihydro-1,4-benzodioxin-6-yl)pyridine | Drug Info | [15] | |||
52 | 3-(2-Chloro-1,1-dimethyl-2-phenyl-ethyl)-pyridine | Drug Info | [13] | |||
53 | 3-(3,4-dihydronaphthalen-2-yl)pyridine | Drug Info | [10] | |||
54 | 3-(3-Benzyl-6-methoxynaphthalen-2-yl)pyridine | Drug Info | [16] | |||
55 | 3-(3-Benzylnaphthalen-2-yl)pyridine | Drug Info | [16] | |||
56 | 3-(3-methyl-3,4-dihydronaphthalen-2-yl)pyridine | Drug Info | [10] | |||
57 | 3-(4-ethyl-3,4-dihydronaphthalen-2-yl)pyridine | Drug Info | [10] | |||
58 | 3-(4-methyl-3,4-dihydronaphthalen-2-yl)pyridine | Drug Info | [10] | |||
59 | 3-(5,6,7,8-Tetrahydronaphthalen-2-yl)pyridine | Drug Info | [15] | |||
60 | 3-(5-Bromo-6-methoxy-naphthalen-2-yl)-pyridine | Drug Info | [11] | |||
61 | 3-(5-Chloro-6-methoxy-naphthalen-2-yl)-pyridine | Drug Info | [11] | |||
62 | 3-(5-methoxy-1H-inden-2-yl)pyridine | Drug Info | [10] | |||
63 | 3-(6-Bromo-naphthalen-2-yl)-pyridine | Drug Info | [11] | |||
64 | 3-(6-Ethoxy-naphthalen-2-yl)-pyridine | Drug Info | [11] | |||
65 | 3-(6-methoxy-3,4-dihydronaphthalen-2-yl)pyridine | Drug Info | [17] | |||
66 | 3-(6-Methoxy-3-methylnaphthalen-2-yl)pyridine | Drug Info | [17] | |||
67 | 3-(6-Methoxynaphthalen-2-yl)-4-methylpyridine | Drug Info | [17] | |||
68 | 3-(6-Methoxynaphthalen-2-yl)-5-phenylpyridine | Drug Info | [17] | |||
69 | 3-(6-Methoxynaphthalen-2-yl)pyridin-4-amine | Drug Info | [17] | |||
70 | 3-(6-methoxynaphthalen-2-yl)pyridine | Drug Info | [16] | |||
71 | 3-(naphthalen-2-yl)pyridine | Drug Info | [16] | |||
72 | 3-Ethoxy-5-(6-methoxynaphthalen-2-yl)pyridine | Drug Info | [17] | |||
73 | 3-Fluoro-4'-(pyridin-4-ylmethyl)biphenyl-4-ol | Drug Info | [18] | |||
74 | 3-Imidazol-1-yl-quinoline | Drug Info | [11] | |||
75 | 3-Imidazol-1-ylmethyl-1H-indole | Drug Info | [12] | |||
76 | 3-Imidazol-1-ylmethyl-2-isopropyl-1H-indole | Drug Info | [12] | |||
77 | 3-Indan-(1E)-ylidenemethyl-pyridine | Drug Info | [19] | |||
78 | 3-Indan-(1Z)-ylidenemethyl-pyridine | Drug Info | [19] | |||
79 | 3-MeSO2-DDE | Drug Info | [1] | |||
80 | 3-methoxy-5-(6-methoxynaphthalen-2-yl)pyridine | Drug Info | [17] | |||
81 | 3-Phenanthren-9-yl-pyridine | Drug Info | [11] | |||
82 | 3-[(Z)-2-phenylvinyl]pyridine | Drug Info | [10] | |||
83 | 3-[1-(4-Bromobenzyl)-1H-imidazol-5-yl]-1-propanol | Drug Info | [8] | |||
84 | 3-[1-(4-Cyanobenzyl)-1H-imidazol-5-yl]-1-propanol | Drug Info | [8] | |||
85 | 3-[3-(4-Methoxybenzyl)naphthalen-2-yl]pyridine | Drug Info | [16] | |||
86 | 3-[4-Chloro-indan-(1E)-ylidenemethyl]-pyridine | Drug Info | [19] | |||
87 | 3-[4-Chloro-indan-(1Z)-ylidenemethyl]-pyridine | Drug Info | [19] | |||
88 | 3-[4-Fluoro-indan-(1E)-ylidenemethyl]-pyridine | Drug Info | [19] | |||
89 | 3-[4-Methyl-indan-(1E)-ylidenemethyl]-pyridine | Drug Info | [19] | |||
90 | 3-[5-Bromo-indan-(1E)-ylidenemethyl]-pyridine | Drug Info | [19] | |||
91 | 3-[5-Bromo-indan-(1Z)-ylidenemethyl]-pyridine | Drug Info | [19] | |||
92 | 3-[5-Chloro-indan-(1E)-ylidenemethyl]-pyridine | Drug Info | [19] | |||
93 | 3-[5-Chloro-indan-(1Z)-ylidenemethyl]-pyridine | Drug Info | [19] | |||
94 | 3-[5-Ethoxy-indan-(1E)-ylidenemethyl]-pyridine | Drug Info | [19] | |||
95 | 3-[5-Ethoxy-indan-(1Z)-ylidenemethyl]-pyridine | Drug Info | [19] | |||
96 | 3-[5-Fluoro-indan-(1E)-ylidenemethyl]-pyridine | Drug Info | [19] | |||
97 | 3-[5-Fluoro-indan-(1Z)-ylidenemethyl]-pyridine | Drug Info | [19] | |||
98 | 3-[5-Methoxy-indan-(1E)-ylidenemethyl]-pyridine | Drug Info | [19] | |||
99 | 3-[5-Methoxy-indan-(1Z)-ylidenemethyl]-pyridine | Drug Info | [19] | |||
100 | 3-[7-Methoxy-indan-(1E)-ylidenemethyl]-pyridine | Drug Info | [19] | |||
101 | 4'-(Pyridin-4-ylmethyl)biphenyl-3,4-diamine | Drug Info | [18] | |||
102 | 4'-(Pyridin-4-ylmethyl)biphenyl-3,4-diol | Drug Info | [18] | |||
103 | 4'-(Pyridin-4-ylmethyl)biphenyl-3-amine | Drug Info | [18] | |||
104 | 4'-(Pyridin-4-ylmethyl)biphenyl-4-amine | Drug Info | [18] | |||
105 | 4-((1H-imidazol-1-yl)methyl)benzonitrile | Drug Info | [8] | |||
106 | 4-((3',4'-Difluorobiphenyl-4-yl)methyl)pyridine | Drug Info | [18] | |||
107 | 4-(2-Imidazol-1-yl-ethoxy)-benzamide | Drug Info | [9] | |||
108 | 4-(4'-Fluoro-biphenyl-4-ylmethyl)pyridine | Drug Info | [18] | |||
109 | 4-(4-(thiophen-2-yl)benzyl)pyridine | Drug Info | [18] | |||
110 | 4-(4-(thiophen-3-yl)benzyl)pyridine | Drug Info | [18] | |||
111 | 4-(6-methoxy-3,4-dihydronaphthalen-2-yl)pyridine | Drug Info | [10] | |||
112 | 4-(6-Methoxy-3-methylnaphthalen-2-yl)isoquinoline | Drug Info | [17] | |||
113 | 4-(6-Methoxynaphthalen-2-yl)isoquinoline | Drug Info | [17] | |||
114 | 4-Indan-(1Z)-ylidenemethyl-pyridine | Drug Info | [19] | |||
115 | 4-[(3'-Hydroxybiphenyl-4-yl)methyl]pyridine | Drug Info | [18] | |||
116 | 4-[(4'-Hydroxybiphenyl-4-yl)methyl]pyridine | Drug Info | [18] | |||
117 | 4-[5-Bromo-indan-(1E)-ylidenemethyl]-pyridine | Drug Info | [19] | |||
118 | 4-[5-Bromo-indan-(1Z)-ylidenemethyl]-pyridine | Drug Info | [19] | |||
119 | 4-[5-Chloro-indan-(1E)-ylidenemethyl]-pyridine | Drug Info | [19] | |||
120 | 4-[5-Chloro-indan-(1Z)-ylidenemethyl]-pyridine | Drug Info | [19] | |||
121 | 4-[5-Fluoro-indan-(1E)-ylidenemethyl]-pyridine | Drug Info | [19] | |||
122 | 4-[5-Fluoro-indan-(1Z)-ylidenemethyl]-pyridine | Drug Info | [19] | |||
123 | 5-(6-Methoxynaphthalen-2-yl)pyridin-3-ol | Drug Info | [17] | |||
124 | 5-Indan-(1E)-ylidenemethyl-1H-imidazole | Drug Info | [20] | |||
125 | 5-Indan-(1Z)-ylidenemethyl-1H-imidazole | Drug Info | [20] | |||
126 | 5-Naphthalen-2-yl-1H-imidazole | Drug Info | [11] | |||
127 | 5-Naphthalen-2-yl-oxazole | Drug Info | [11] | |||
128 | 5-Pyridin-3-yl-1,3-dihydro-2H-indol-2-one | Drug Info | [15] | |||
129 | 5-Pyridin-3-yl-2,3-dihydro-1H-inden-1-one | Drug Info | [15] | |||
130 | 5-[4-(Pyridin-4-ylmethyl)phenyl]-1H-indole | Drug Info | [18] | |||
131 | 5-[5-Bromo-indan-(1E)-ylidenemethyl]-1H-imidazole | Drug Info | [20] | |||
132 | 5-[5-Bromo-indan-(1Z)-ylidenemethyl]-1H-imidazole | Drug Info | [20] | |||
133 | 5-[5-Fluoro-indan-(1E)-ylidenemethyl]-pyrimidine | Drug Info | [19] | |||
134 | 6-(4-Methylpyridin-3-yl)-2-naphthonitrile | Drug Info | [17] | |||
135 | 6-(pyridin-3-yl)-2-naphthonitrile | Drug Info | [17] | |||
136 | 6-Isoquinolin-4-yl-3,4-dihydroquinolin-2(1H)-one | Drug Info | [15] | |||
137 | 6-Pyridin-3-yl-1,2,3,4-tetrahydronaphthalen-2-ol | Drug Info | [15] | |||
138 | 6-Pyridin-3-yl-3,4-dihydro-1H-quinolin-2-one | Drug Info | [15] | |||
139 | 6-Pyridin-3-yl-3,4-dihydronaphthalen-2(1H)-one | Drug Info | [15] | |||
140 | 6-Pyridin-3-yl-3,4-dihydroquinoline-2(1H)-thione | Drug Info | [15] | |||
141 | 6-Pyridin-3-yl-naphthalen-2-ol | Drug Info | [11] | |||
142 | 6-[4-(Pyridin-4-ylmethyl)phenyl]naphthalen-2-ol | Drug Info | [18] | |||
143 | 7-(1-(1H-imidazol-1-yl)ethyl)-9H-fluoren-2-ol | Drug Info | [21] | |||
144 | 7-Pyridin-3-yl-2H-1,4-benzothiazin-3(4H)-one | Drug Info | [15] | |||
145 | BENZYLIMIDAZOLE | Drug Info | [8] | |||
146 | Methyl 3-(1-Benzyl-1H-imidazol-5-yl)-propanoate | Drug Info | [8] | |||
147 | METYRAPOL | Drug Info | [13] | |||
148 | N-(4'-Isonicotinoylbiphenyl-3-yl)acetamide | Drug Info | [18] | |||
149 | R-fadrozole | Drug Info | [8] | |||
150 | SL125 | Drug Info | [22] | |||
Modulator | [+] 1 Modulator drugs | + | ||||
1 | Osilodrostat | Drug Info | [7] |
Cell-based Target Expression Variations | Top | |||||
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Cell-based Target Expression Variations |
Drug Binding Sites of Target | Top | |||||
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Ligand Name: Cholic acid | Ligand Info | |||||
Structure Description | Human CYP11B1 mutant in complex with metyrapone | PDB:7E7F | ||||
Method | X-ray diffraction | Resolution | 1.40 Å | Mutation | Yes | [23] |
PDB Sequence |
VPRTVLPFEA
40 MPRRPGNRRN50 RLNQIRREQG60 YEDLHLEVHQ70 TFQELGPIFR80 YDLGGAGMVC 90 VMLPEDVEKL100 QQVDSLHPHR110 MSLEPWVAYR120 QHRGHKCGVF130 LLNGPEWRFN 140 RLRLNPEVLS150 PNAVQRFLPM160 VDAVARDFSQ170 ALKKKVLQNA180 RGSLTLDVQP 190 SIFHYTIEAS200 NLALFGERLG210 LVGHSPSSAS220 LNFLHALEVM230 FKSTVQLMFM 240 PRSNSRNTSP250 KVWKEHFEAW260 DCIFQYGDNC270 IQKIYQELAF280 SRPQQYTSIV 290 AELLLNAELS300 PDAIKANSME310 LTAGSVDTTV320 FPLLMTLFEL330 ARNPNVQQAL 340 RQESLAAAAS350 ISEHPQKATT360 ELPLLRAALK370 ETLRLYPVGL380 FLERVASSDL 390 VLQNYHIPAG400 TLVRVFLYSL410 GRNPALFPRP420 ERYNPQRWLD430 IRGSGRNFYH 440 VPFGFGMRQC450 LGRRLAEAEM460 LLLLHHVLKH470 LQVETLTQED480 IKMVYSFILR 490 PSMFPLLTFR500 AI
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ARG44
4.080
LEU52
4.985
ARG56
3.255
TYR61
3.596
LEU64
3.915
TYR81
2.568
LEU83
3.493
MET88
4.027
MET111
4.477
ALA118
3.770
HIS122
3.933
MET238
3.957
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Ligand Name: Metyrapone | Ligand Info | |||||
Structure Description | Human CYP11B1 mutant in complex with metyrapone | PDB:7E7F | ||||
Method | X-ray diffraction | Resolution | 1.40 Å | Mutation | Yes | [23] |
PDB Sequence |
VPRTVLPFEA
40 MPRRPGNRRN50 RLNQIRREQG60 YEDLHLEVHQ70 TFQELGPIFR80 YDLGGAGMVC 90 VMLPEDVEKL100 QQVDSLHPHR110 MSLEPWVAYR120 QHRGHKCGVF130 LLNGPEWRFN 140 RLRLNPEVLS150 PNAVQRFLPM160 VDAVARDFSQ170 ALKKKVLQNA180 RGSLTLDVQP 190 SIFHYTIEAS200 NLALFGERLG210 LVGHSPSSAS220 LNFLHALEVM230 FKSTVQLMFM 240 PRSNSRNTSP250 KVWKEHFEAW260 DCIFQYGDNC270 IQKIYQELAF280 SRPQQYTSIV 290 AELLLNAELS300 PDAIKANSME310 LTAGSVDTTV320 FPLLMTLFEL330 ARNPNVQQAL 340 RQESLAAAAS350 ISEHPQKATT360 ELPLLRAALK370 ETLRLYPVGL380 FLERVASSDL 390 VLQNYHIPAG400 TLVRVFLYSL410 GRNPALFPRP420 ERYNPQRWLD430 IRGSGRNFYH 440 VPFGFGMRQC450 LGRRLAEAEM460 LLLLHHVLKH470 LQVETLTQED480 IKMVYSFILR 490 PSMFPLLTFR500 AI
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Click to View More Binding Site Information of This Target with Different Ligands |
Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Tissue Distribution
Human Pathway Affiliation
Biological Network Descriptors
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There is no similarity protein (E value < 0.005) for this target
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Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
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KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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Steroid hormone biosynthesis | hsa00140 | Affiliated Target |
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Class: Metabolism => Lipid metabolism | Pathway Hierarchy | ||
Cortisol synthesis and secretion | hsa04927 | Affiliated Target |
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Class: Organismal Systems => Endocrine system | Pathway Hierarchy |
Degree | 7 | Degree centrality | 7.52E-04 | Betweenness centrality | 6.98E-05 |
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Closeness centrality | 1.46E-01 | Radiality | 1.18E+01 | Clustering coefficient | 5.24E-01 |
Neighborhood connectivity | 1.03E+01 | Topological coefficient | 4.47E-01 | Eccentricity | 12 |
Download | Click to Download the Full PPI Network of This Target | ||||
Chemical Structure based Activity Landscape of Target | Top |
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Drug Property Profile of Target | Top | |
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(1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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(5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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"RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five |
Co-Targets | Top | |||||
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Co-Targets |
Target Poor or Non Binders | Top | |||||
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Target Poor or Non Binders |
Target Profiles in Patients | Top | |||||
---|---|---|---|---|---|---|
Target Expression Profile (TEP) |
Target Affiliated Biological Pathways | Top | |||||
---|---|---|---|---|---|---|
BioCyc | [+] 3 BioCyc Pathways | + | ||||
1 | Superpathway of steroid hormone biosynthesis | |||||
2 | Glucocorticoid biosynthesis | |||||
3 | Mineralocorticoid biosynthesis | |||||
KEGG Pathway | [+] 2 KEGG Pathways | + | ||||
1 | Steroid hormone biosynthesis | |||||
2 | Metabolic pathways | |||||
Pathwhiz Pathway | [+] 1 Pathwhiz Pathways | + | ||||
1 | Steroidogenesis | |||||
Reactome | [+] 2 Reactome Pathways | + | ||||
1 | Glucocorticoid biosynthesis | |||||
2 | Endogenous sterols | |||||
WikiPathways | [+] 4 WikiPathways | + | ||||
1 | Metapathway biotransformation | |||||
2 | Oxidation by Cytochrome P450 | |||||
3 | Metabolism of steroid hormones and vitamin D | |||||
4 | Corticotropin-releasing hormone |
Target-Related Models and Studies | Top | |||||
---|---|---|---|---|---|---|
Target Validation |
References | Top | |||||
---|---|---|---|---|---|---|
REF 1 | Effects of 3-MeSO2-DDE and some CYP inhibitors on glucocorticoid steroidogenesis in the H295R human adrenocortical carcinoma cell line. Toxicol In Vitro. 2002 Apr;16(2):113-21. | |||||
REF 2 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 8311). | |||||
REF 3 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
REF 4 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000824) | |||||
REF 5 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5224). | |||||
REF 6 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 012911. | |||||
REF 7 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020 | |||||
REF 8 | Synthesis, biological evaluation, and molecular modeling of 1-benzyl-1H-imidazoles as selective inhibitors of aldosterone synthase (CYP11B2). J Med Chem. 2010 Feb 25;53(4):1712-25. | |||||
REF 9 | Selective thromboxane synthetase inhibitors. 1. 1-[(Aryloxy)alkyl]-1H-imidazoles. J Med Chem. 1985 Oct;28(10):1427-32. | |||||
REF 10 | Synthesis and evaluation of heteroaryl-substituted dihydronaphthalenes and indenes: potent and selective inhibitors of aldosterone synthase (CYP11B... J Med Chem. 2006 Apr 6;49(7):2222-31. | |||||
REF 11 | Heteroaryl-substituted naphthalenes and structurally modified derivatives: selective inhibitors of CYP11B2 for the treatment of congestive heart fa... J Med Chem. 2005 Oct 20;48(21):6632-42. | |||||
REF 12 | Selective thromboxane synthetase inhibitors. 2. 3-(1H-imidazol-1-ylmethyl)-2-methyl-1H-indole-1-propanoic acid and analogues. J Med Chem. 1986 Mar;29(3):342-6. | |||||
REF 13 | Structure-activity relationship study of the inhibition of adrenal cortical 11 beta-hydroxylase by new metyrapone analogues. J Med Chem. 1984 Jan;27(1):15-9. | |||||
REF 14 | Development and evaluation of a pharmacophore model for inhibitors of aldosterone synthase (CYP11B2). Bioorg Med Chem Lett. 2006 Jan 1;16(1):25-30. | |||||
REF 15 | In vivo active aldosterone synthase inhibitors with improved selectivity: lead optimization providing a series of pyridine substituted 3,4-dihydro-... J Med Chem. 2008 Dec 25;51(24):8077-87. | |||||
REF 16 | Novel aldosterone synthase inhibitors with extended carbocyclic skeleton by a combined ligand-based and structure-based drug design approach. J Med Chem. 2008 Oct 9;51(19):6138-49. | |||||
REF 17 | Overcoming undesirable CYP1A2 inhibition of pyridylnaphthalene-type aldosterone synthase inhibitors: influence of heteroaryl derivatization on pote... J Med Chem. 2008 Aug 28;51(16):5064-74. | |||||
REF 18 | Replacement of imidazolyl by pyridyl in biphenylmethylenes results in selective CYP17 and dual CYP17/CYP11B1 inhibitors for the treatment of prosta... J Med Chem. 2010 Aug 12;53(15):5749-58. | |||||
REF 19 | Synthesis and evaluation of (pyridylmethylene)tetrahydronaphthalenes/-indanes and structurally modified derivatives: potent and selective inhibitor... J Med Chem. 2005 Mar 10;48(5):1563-75. | |||||
REF 20 | Synthesis and evaluation of imidazolylmethylenetetrahydronaphthalenes and imidazolylmethyleneindanes: potent inhibitors of aldosterone synthase. J Med Chem. 2005 Mar 24;48(6):1796-805. | |||||
REF 21 | Synthesis, biological evaluation, and molecular modeling studies of methylene imidazole substituted biaryls as inhibitors of human 17alpha-hydroxyl... Bioorg Med Chem. 2008 Aug 15;16(16):7715-27. | |||||
REF 22 | Reduction of cell proliferation induced by PD166866: an inhibitor of the basic fibroblast growth factor. J Exp Clin Cancer Res. 2007 Sep;26(3):405-9. | |||||
REF 23 | Spatially restricted substrate-binding site of cortisol-synthesizing CYP11B1 limits multiple hydroxylations and hinders aldosterone synthesis. Curr Res Struct Biol. 2021 Aug 26;3:192-205. |
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