Natural Product (NP) Details

General Information of the NP (ID: NP5296)
Name
Exemestane
Synonyms
EXEMESTANE; 107868-30-4; Aromasin; Aromasine; 6-Methyleneandrosta-1,4-diene-3,17-dione; Fce 24304; Exemestano; Exemestanum; Exemestanum [INN-Latin]; Exemestano [INN-Spanish]; FCE-24304; 6-Methylene-androsta-1,4-diene-3,17-dione; UNII-NY22HMQ4BX; FCE24304; Androsta-1,4-diene-3,17-dione, 6-methylene-; 6-methylideneandrosta-1,4-diene-3,17-dione; NY22HMQ4BX; PNU-155971; CHEBI:4953; (8R,9S,10R,13S,14S)-10,13-dimethyl-6-methylene-7,8,9,10,11,12,13,14,15,16-decahydro-3H-cyclopenta[a]phenanthrene-3,17(6H)-dione; Aromasil; NSC713563; (8R,9S,10R,13S,14S)-10,13-dimethyl-6-methylidene-7,8,9,11,12,14,15,16-octahydrocyclopenta[a]phenanthrene-3,17-dione; EXE; DSSTox_CID_3037; DSSTox_RID_76844; DSSTox_GSID_23037; (8R,9S,10R,13S,14S)-10,13-Dimethyl-6-methylene-7,8,9,11,12,13,15,16-octahydro-6H-cyclopenta[a]phenanthrene-3,17(10H,14H)-dione; Exemestane [USAN:INN:BAN]; Nikidess; (8alpha,10alpha,13alpha)-6-Methylideneandrosta-1,4-Diene-3,17-Dione; Aromasin (TN); (8R,9S,10R,13S,14S)-10,13-dimethyl-6-methylene-7,8,9,10,11,12,13,14,15,16-decahydro-3H-cyclopenta[a]phenanthrene-3,17(6H)-dione.; SMR000466314; CAS-107868-30-4; HSDB 7463; Curator_000009; Exemestane (JAN/USP/INN); CCRIS 9351; NCGC00095289-01; Exemestane; aromasin; Exemestane, Aromasin; PNU 155971; PubChem5810; SCHEMBL6215; Aromasin (Pharmacia Upjohn); Exemestane(FCE 24304); MLS000759419; MLS001424062; GTPL7073; 6-Methylenandrosta-1,17-dione; CHEMBL1200374; DTXSID5023037; Exemestane, >=98% (HPLC); AOB5604; SYN3023; BCPP000235; HMS2051J04; HMS3713H12; BCP23353; ZINC3973334; Tox21_111499; ANW-63402; BDBM50398447; MFCD00866994; s1196; AKOS015840113; AKOS015895161; Tox21_111499_1; AC-2171; BCP9000676; CCG-100995; CS-1766; DB00990; KS-5136; NC00245; NSC 758907; NSC-713563; NCGC00271596-03; 6-methylenandrost-1,4-dien-3,17-dione; AS-31053; CPD000466314; HY-13632; BCP0726000226; 6-Methylen-androst-1,4-diene-3,17-dione; AB0063735; E0941; C08162; D00963; Z-4332; AB00639936-06; AB00639936-08; AB00639936-09; AB00639936-10; AB00639936_11; 868E304; Q418819; SR-01000759393; SR-01000759393-4; BRD-K33425534-001-12-5; Exemestane, European Pharmacopoeia (EP) Reference Standard; Exemestane, United States Pharmacopeia (USP) Reference Standard; Exemestane, Pharmaceutical Secondary Standard; Certified Reference Material; Exemestane for system suitability, European Pharmacopoeia (EP) Reference Standard; (1S,2R,10R,11S,15S)-2,15-dimethyl-8-methylidenetetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadeca-3,6-diene-5,14-dione; EXM
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Species Origin Homo sapiens ...     Click to Show/Hide
Homo sapiens
Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens
Disease Breast cancer [ICD-11: 2C60] Approved [1]
Structure
Click to Download Mol
2D MOL

3D MOL

ADMET Property
Absporption
Caco-2 Permeability
 -4.877
 
MDCK Permeability
 -4.685
 
PAMPA
 - - -
 
HIA
 - - -
 
Distribution
VDss
 0.406
 
PPB
 84.6%
 
BBB
 - - -
 
Metabolism
CYP1A2 inhibitor
 - - -
CYP1A2 substrate
 +
CYP2C19 inhibitor
 - - -
CYP2C19 substrate
 - -
CYP2C9 inhibitor
 - - -
CYP2C9 substrate
 - - -
CYP2D6 inhibitor
 - - -
CYP2D6 substrate
 - - -
CYP3A4 inhibitor
 -
CYP3A4 substrate
 +++
CYP2B6 inhibitor
 - -
CYP2B6 substrate
 - - -
CYP2C8 inhibitor
 +++
HLM Stability
 ++
 
Excretion
CLplasma
 10.126
 
T1/2
 0.924
Toxicity
DILI
 -
 
Rat Oral Acute Toxicity
 ++
 
FDAMDD
 +++
 
Respiratory
 +++
 
Human Hepatotoxicity
 ++
 
Ototoxicity
 -
 
Drug-induced Nephrotoxicity
 ++
 
Drug-induced Neurotoxicity
 ++
 
Hematotoxicity
 +
 
Genotoxicity
 +++
 
Tips: 1. For the classification endpoints, the prediction probability values are transformed into six symbols: 0-0.1 (- - -), 0.1-0.3 (- -), 0.3-0.5 (-), 0.5-0.7 (+), 0.7-0.9 (++), and 0.9-1.0 (+++). 2. Additionally, the corresponding relationships of the three labels are as follows: excellent; medium; poor.
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    Click to Show/Hide the Molecular Information and External Link(s) of This Natural Product
Formula
C20H24O2
PubChem CID
60198
Canonical SMILES
CC12CCC3C(C1CCC2=O)CC(=C)C4=CC(=O)C=CC34C
InChI
1S/C20H24O2/c1-12-10-14-15-4-5-18(22)20(15,3)9-7-16(14)19(2)8-6-13(21)11-17(12)19/h6,8,11,14-16H,1,4-5,7,9-10H2,2-3H3/t14-,15-,16-,19+,20-/m0/s1
InChIKey
BFYIZQONLCFLEV-DAELLWKTSA-N
CAS Number
CAS 107868-30-4
ChEBI ID
CHEBI:4953
TTD Drug ID
D0D2VS
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Drug(s) Whose Efficacy can be Enhanced by This NP
          Triptorelin + Cisplatin     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [2]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression VEGFA  Molecule Info 
Pathway MAP
                    In-vivo Model Ascites OT (5*106) cells were intraperitoneally transplanted in female Wistar rats.
                    Experimental
                    Result(s)		 Triptorelin and exemestane increase antitumor activity of cisplatin in respect to the transplantable malignant ascites OT and significantly increase survival of animals, especially when triptorelin and cisplatin are used in combination.
Target and Pathway
Target(s) Aromatase (CYP19A1)  Molecule Info  [3]
BioCyc Superpathway of steroid hormone biosynthesis Click to Show/Hide
2 Estradiol biosynthesis II
3 Estradiol biosynthesis I
KEGG Pathway Steroid hormone biosynthesis Click to Show/Hide
2 Metabolic pathways
3 Ovarian steroidogenesis
NetPath Pathway FSH Signaling Pathway Click to Show/Hide
Panther Pathway Androgen/estrogene/progesterone biosynthesis Click to Show/Hide
Pathwhiz Pathway Androgen and Estrogen Metabolism Click to Show/Hide
Reactome Endogenous sterols Click to Show/Hide
WikiPathways Metapathway biotransformation Click to Show/Hide
2 Tryptophan metabolism
3 Oxidation by Cytochrome P450
4 Ovarian Infertility Genes
5 Metabolism of steroid hormones and vitamin D
6 FSH signaling pathway
7 Integrated Breast Cancer Pathway
8 Phase 1 - Functionalization of compounds
References
Reference 1 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: 7073).
Reference 2 The antitumor efficacy of cisplatin in combination with triptorelin and exemestane therapy for an ovarian cancer ascites model in Wistar rats. Exp Oncol. 2015 Mar;37(1):30-5.
Reference 3 Aromatase inhibitors--theoretical concept and present experiences in the treatment of endometriosis. Zentralbl Gynakol. 2003 Jul-Aug;125(7-8):247-51.
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