ABIRATERONE

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Synonyms
Status
Molecule Category Free-form
ATC L02BX03
UNII G819A456D0
EPA CompTox DTXSID80879993

Structure

InChI Key GZOSMCIZMLWJML-VJLLXTKPSA-N
Smiles C[C@]12CC[C@H](O)CC1=CC[C@@H]1[C@@H]2CC[C@]2(C)C(c3cccnc3)=CC[C@@H]12
InChI
InChI=1S/C24H31NO/c1-23-11-9-18(26)14-17(23)5-6-19-21-8-7-20(16-4-3-13-25-15-16)24(21,2)12-10-22(19)23/h3-5,7,13,15,18-19,21-22,26H,6,8-12,14H2,1-2H3/t18-,19-,21-,22-,23-,24+/m0/s1

Physicochemical Descriptors

Property Name Value
Molecular Formula C24H31NO
Molecular Weight 349.52
AlogP 5.4
Hydrogen Bond Acceptor 2.0
Hydrogen Bond Donor 1.0
Number of Rotational Bond 1.0
Polar Surface Area 33.12
Molecular species NEUTRAL
Aromatic Rings 1.0
Heavy Atoms 26.0

Bioactivity

Mechanism of Action Action Reference
Androgen Receptor antagonist ANTAGONIST PubMed PubMed PubMed PubMed PubMed
Protein: Cytochrome P450 17A1
Description: Steroid 17-alpha-hydroxylase/17,20 lyase
Organism : Homo sapiens
P05093 ENSG00000148795
Protein: Androgen Receptor
Description: Androgen receptor
Organism : Homo sapiens
P10275 ENSG00000169083
Targets EC50(nM) IC50(nM) Kd(nM) Ki(nM) Inhibition(%)
Enzyme Cytochrome P450 Cytochrome P450 family 1 Cytochrome P450 family 1A Cytochrome P450 1A2
- - - - 34-93
Enzyme Cytochrome P450 Cytochrome P450 family 11 Cytochrome P450 family 11B Cytochrome P450 11B1
- 1608-1610 - - -
Enzyme Cytochrome P450 Cytochrome P450 family 11 Cytochrome P450 family 11B Cytochrome P450 11B2
- 1750-1751 - - -
Enzyme Cytochrome P450 Cytochrome P450 family 17 Cytochrome P450 family 17A Cytochrome P450 17A1
- 3-800 - - 74-100
Enzyme Cytochrome P450 Cytochrome P450 family 2 Cytochrome P450 family 2B Cytochrome P450 2B6
- - - - 2-11
Enzyme Cytochrome P450 Cytochrome P450 family 2 Cytochrome P450 family 2C Cytochrome P450 2C19
- - - - 3-92
Enzyme Cytochrome P450 Cytochrome P450 family 2 Cytochrome P450 family 2C Cytochrome P450 2C9
- - - - 17-83
Enzyme Cytochrome P450 Cytochrome P450 family 2 Cytochrome P450 family 2D Cytochrome P450 2D6
- - - - 7-79
Enzyme Cytochrome P450 Cytochrome P450 family 21 Cytochrome P450 family 21A Cytochrome P450 21A2
- 32 - - -
Enzyme Cytochrome P450 Cytochrome P450 family 3 Cytochrome P450 family 3A Cytochrome P450 3A4
- 230-2704 - - 4-27
Assay Description Organism Bioactivity Reference
Ability to inhibit the C17,20-lyase enzyme by 50% using 17-alpha-hydroxyprogesterone as substrate. None 2.9 nM
In vitro cytochrome P450 17A1 inhibition was assayed using the rapid acetic acid releasing assay (AARA), utilizing intact P450c17-expressing Escherichia coli or P450c17-LNCaP cells as the enzyme source. None 800.0 nM
Inhibition of human progesterone 17-alpha-hydroxylase. Homo sapiens 4.0 nM
Ability to inhibit the Steroid 17-alpha-hydroxylase/17,20 lyase enzyme by 50%. None 4.0 nM
Inhibition of human Steroid 17-alpha-hydroxylase/17,20 lyase Homo sapiens 1.0 nM
In vitro inhibitory concentration against Cytochrome P450 17 expressed in Escherichia coli Homo sapiens 800.0 nM
Inhibition of human CYP17 expressed in Escherichia coli Homo sapiens 72.0 nM
Inhibition of hepatic CYP1A2 at 1 uM None 36.0 %
Inhibition of hepatic CYP1A2 at 10 uM None 53.0 %
Inhibition of hepatic CYP2C9 at 1 uM None 17.0 %
Inhibition of hepatic CYP2C9 at 10 uM None 51.0 %
Inhibition of hepatic CYP2C19 at 1 uM None 3.0 %
Inhibition of hepatic CYP2C19 at 10 uM None 7.0 %
Inhibition of hepatic CYP3A4 at 1 uM None 7.0 %
Inhibition of hepatic CYP3A4 at 10 uM None 7.0 %
Inhibition of human CYP17 expressed in Escherichia coli co-expressed with NADPH-P450 reductase Homo sapiens 72.0 nM
Inhibition of Sprague-Dawley rat testicular CYP17 Rattus norvegicus 220.0 nM
Inhibition of recombinant CYP3A4 at 1 uM None 4.0 %
Inhibition of recombinant CYP3A4 at 10 uM None 25.0 %
Inhibition of recombinant CYP1A2 at 1 uM None 36.0 %
Inhibition of recombinant CYP1A2 at 10 uM None 53.0 %
Inhibition of recombinant CYP2C9 at 1 uM None 17.0 %
Inhibition of recombinant CYP2C9 at 10 uM None 51.0 %
Inhibition of recombinant CYP2C19 at 1 uM None 3.0 %
Inhibition of recombinant CYP2C19 at 10 uM None 21.0 %
Inhibition of recombinant CYP2B6 at 1 uM None 2.0 %
Inhibition of recombinant CYP2B6 at 10 uM None 11.0 %
Inhibition of recombinant CYP2D6 at 1 uM None 7.0 %
Inhibition of recombinant CYP2D6 at 10 uM None 7.0 %
Inhibition of human recombinant CYP17 expressed in Escherichia coli coexpressing NADPH-P450 reductase Homo sapiens 72.0 nM
Inhibition of hepatic CYP3A4 expressed in insect microsomes at 1 uM None 27.0 %
Inhibition of hepatic CYP1A2 expressed in insect microsomes at 1 uM None 36.0 %
Inhibition of hepatic CYP2B6 expressed in insect microsomes at 1 uM None 2.0 %
Inhibition of hepatic CYP2D6 expressed in insect microsomes at 1 uM None 7.0 %
Inhibition of human CYP17 expressed in Escherichia coli coexpressed with cytochrome P450 reductase Homo sapiens 72.0 nM
Inhibition of human CYP17 expressed in Escherichia coli coexpressing NADPH-P450 reductase Homo sapiens 72.0 nM
Inhibition of human CYP17 expressed in Escherichia coli coexpressing NADPH-P450 reductase Homo sapiens 72.0 nM
Inhibition of human CYP17 expressed in Escherichia coli Homo sapiens 72.0 nM
Inhibition of human CYP17 expressed in Escherichia coli using progesterone substrate Homo sapiens 72.0 nM
Inhibition of human CYP17 expressed in Escherichia coli co-expressing rat NADPH-P450-reductase using progesterone as substrate Homo sapiens 72.0 nM
Inhibition of human CYP17 expressed in Escherichia coli using 1,2[3H]-progesterone as substrate in presence of NADPH Homo sapiens 72.0 nM
Inhibition of Wistar rat testicular C17,20-lyase using [3H]17-hydroxyprogesterone as substrate preincubated for 20 mins Rattus norvegicus 12.5 nM
Irreversible inhibition of human cytochrome P450 17alpha Homo sapiens 5.0 nM
Inhibition of human CYP17 expressed in Escherichia coli Homo sapiens 800.0 nM
Inhibition of Wistar rat testicular C17,20-lyase assessed as androst-4-ene-3,17-dione formation using [3H]17-hydroxyprogesterone as substrate in presence of NADPH Rattus norvegicus 12.5 nM
Inhibition of CYP17 in human testicular microsomes using 17alpha-hydroxypregnenolone as substrate assessed as decrease in DHEA levels after 90 mins by ELISA Homo sapiens 11.0 nM
Inhibition of CYP17 in human testicular microsomes using 17alpha-hydroxypregnenolone as substrate assessed as decrease in DHEA levels at 10 nM after 90 mins by ELISA relative to control Homo sapiens 80.0 %
Inhibition of CYP17 in human H295R cells assessed as decrease in testosterone levels after 24 hrs by ELISA Homo sapiens 15.0 nM
Inhibition of Sprague-Dawley rat adrenal mitochondrial CYP11B assessed as decrease in conversion of 11-deoxycortisol to cortisol at 100 nM incubated for 60 mins by ELISA relative to control Rattus norvegicus 32.0 %
Inhibition of human CYP21 transfected in HEK293 cells assessed as decrease in conversion of progesterone to 11-deoxycorticosterone preincubated for 5 hrs followed by progesterone addition measured after 20 hrs by ELISA Homo sapiens 50.0 %
Inhibitory Activity Assay: The inhibition of CYP17A1 by the test compounds was evaluated using a recombinant enzyme. Human CYP17A1 was expressed in E. coli (Ehmer, P. B. et al.; J. Steroid Biochem. Mol. Biol., 75, 57-63 (2000)). The microsomal fraction and 140 μL of phosphate buffer (50 mM Na phosphate, 1 mM MgCl2, 0.1 mM EDTA, 0.1 mM dithiothreitol, pH 7.4) were preincubated separately with a mixture of progesterone (24.95 μM) and 3H-progesterone (0.05 μM, 101.3 Ci/mmol), 50 μM of an NADPH regeneration system (in phosphate buffer with 10 mM NADP+, 100 mM glucose 6-phosphate and 2.5 U of glucose 6-phosphate dehydrogenase) and the appropriate test substances (in 5 μl of DMSO) at 37° C. for 5 minutes. The reaction was started by addition of the enzyme and, after 30 minutes of incubation at 37° C., stopped by addition of 50 μl of 1N hydrochloric acid.The steroids were extracted with ethyl acetate. After evaporation of the organic phase, the steroids were taken up in acetonitrile. Homo sapiens 29.0 nM
Inhibition of CYP17 in Sprague-Dawley rat testes microsomes using 17-alpha hydroxyprogesterone as substrate and NADPH as cofactor pretreated for 5 mins followed by substrate and cofactor addition after 60 mins by LC/Ms analysis Rattus norvegicus 24.7 nM
Inhibition of recombinant human CYP17 expressed in human A549 cell membranes using 17-alpha hydroxyprogesterone as substrate and NADPH as cofactor pretreated for 5 mins followed by substrate and cofactor addition after 60 mins by LC/MS analysis Homo sapiens 35.8 nM
Inhibition of human hepatic CYP1A2 at 1 uM relative to control Homo sapiens 34.0 %
Inhibition of human hepatic CYP1A2 at 10 uM relative to control Homo sapiens 92.5 %
Inhibition of human hepatic CYP2C9 at 1 uM relative to control Homo sapiens 31.6 %
Inhibition of human hepatic CYP2C9 at 10 uM relative to control Homo sapiens 82.5 %
Inhibition of human hepatic CYP2C19 at 1 uM relative to control Homo sapiens 39.6 %
Inhibition of human hepatic CYP2C19 at 10 uM relative to control Homo sapiens 91.6 %
Inhibition of human hepatic CYP2D6 at 1 uM relative to control Homo sapiens 10.4 %
Inhibition of human hepatic CYP2D6 at 10 uM relative to control Homo sapiens 78.5 %
Inhibition of CYP17 in human NCI-H295R cells assessed as reduction in testosterone production at 1 uM measured after 72 hrs relative to control Homo sapiens 74.0 %
Inhibition of C-terminal His-tagged recombinant human CYP17A1delta19H mutant expressed in Escherichia coli DH5alpha assessed as decrease in progesterone hydroxylation preincubated for 3 mins followed by NADPH addition measured after 10 mins in presence of cytochrome p450 reductase by LC-MS/MS method Homo sapiens 4.94 nM
Inhibition of C-terminal His-tagged recombinant human CYP21A2deltaH mutant expressed in Escherichia coli DH5alpha assessed as decrease in progesterone hydroxylation preincubated for 3 mins followed by NADPH addition measured after 10 mins in presence of cytochrome p450 reductase by LC-MS/MS method Homo sapiens 32.4 nM
Inhibition of C-terminal His-tagged recombinant human CYP3A4 assessed as decrease in metabolism of luciferin isopropyl alcohol preincubated for 3 mins followed by NADPH addition measured after 30 mins Homo sapiens 230.0 nM
Inhibition of C-terminal His-tagged recombinant human CYP17A1delta19H mutant expressed in Escherichia coli JM109 cells assessed as decrease in progesterone hydroxylation in presence of cytochrome P450 reductase by HPLC-UV method Homo sapiens 9.4 nM
Inhibition of human membrane bound C-terminal His4-tagged CYP17A1 delta19H mutant assessed as reduction in progesterone hydroxylation preincubated for 3 mins followed by NADPH addition measured after 10 mins in presence of NADPH-cytochrome p450 reductase by HPLC method Homo sapiens 130.0 nM
Inhibition of human membrane bound C-terminal His4-tagged CYP21A2 delta19H mutant assessed as reduction in progesterone hydroxylation measured after 10 mins in presence of NADPH/NADPH-cytochrome p450 reductase by GC/MS method Homo sapiens 296.0 nM
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of Caco-2 cells at 10 uM after 48 hours by high content imaging Homo sapiens 1.13 %
Inhibition of C-myc/DDK tagged human CYP17A1 expressed in HEK293T cells assessed as reduction in formation of 17-OHP at 10 uM incubated for 30 mins by LC-MS/MS analysis Homo sapiens 100.0 %
Inhibition of CYP17 (unknown origin) Homo sapiens 48.0 nM
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate Severe acute respiratory syndrome coronavirus 2 -3.97 % SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate Severe acute respiratory syndrome coronavirus 2 -1.896 %
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Chlorocebus sabaeus 0.28 % Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Chlorocebus sabaeus 0.01 % Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Chlorocebus sabaeus 0.28 % Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Chlorocebus sabaeus 0.01 %

Cross References

Resources Reference
ChEBI 68642
ChEMBL CHEMBL254328
DrugBank DB05812
FDA SRS G819A456D0
Guide to Pharmacology 6745
PDB AER
PharmGKB PA166123407
PubChem 132971
SureChEMBL SCHEMBL61108
ZINC ZINC000003797541
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