Details of the Drug

General Information of Drug (ID: DMDH9KX)

Drug Name
Megestrol
Synonyms
Chronopil; Megestrolo; Megestrolo [DCIT]; Chronopil (TN); Megace (TN); Megestrol (INN); Megestrol [INN:BAN]; Megestrolum [INN-Latin]; (8R,9S,10R,13S,14S,17R)-17-acetyl-17-hydroxy-6,10,13-trimethyl-2,8,9,11,12,14,15,16-octahydro-1H-cyclopenta[a]phenanthren-3-one; 17-Hydroxy-6-methylpregna-4,6-diene-3,20-dione
Indication
Disease Entry ICD 11 Status REF
Breast cancer 2C60-2C65 Approved [1]
Therapeutic Class
Anticancer Agents
ATC Code
G03AC05: Megestrol
G03AC: Progestogens
G03A: HORMONAL CONTRACEPTIVES FOR SYSTEMIC USE
G03: SEX HORMONES AND MODULATORS OF THE GENITAL SYSTEM
G: GENITO URINARY SYSTEM AND SEX HORMONES
G03DB02: Megestrol
G03DB: Pregnadien derivatives
G03D: PROGESTOGENS
G03: SEX HORMONES AND MODULATORS OF THE GENITAL SYSTEM
G: GENITO URINARY SYSTEM AND SEX HORMONES
L02AB01: Megestrol
L02AB: Progestogens
L02A: HORMONES AND RELATED AGENTS
L02: ENDOCRINE THERAPY
L: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 342.5
Logarithm of the Partition Coefficient (xlogp) 2.6
Rotatable Bond Count (rotbonds) 1
Hydrogen Bond Donor Count (hbonddonor) 1
Hydrogen Bond Acceptor Count (hbondacc) 3
ADMET Property
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 4: low solubility and low permeability [2]
Bioavailability
90% of drug becomes completely available to its intended biological destination(s) [3]
Elimination
60% of drug is excreted from urine in the unchanged form [2]
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 23.224 micromolar/kg/day [4]
Water Solubility
The ability of drug to dissolve in water is measured as 0.002 mg/mL [2]
Chemical Identifiers
Formula
C22H30O3
IUPAC Name
(8R,9S,10R,13S,14S,17R)-17-acetyl-17-hydroxy-6,10,13-trimethyl-2,8,9,11,12,14,15,16-octahydro-1H-cyclopenta[a]phenanthren-3-one
Canonical SMILES
CC1=C[C@@H]2[C@H](CC[C@]3([C@H]2CC[C@@]3(C(=O)C)O)C)[C@@]4(C1=CC(=O)CC4)C
InChI
InChI=1S/C22H30O3/c1-13-11-16-17(20(3)8-5-15(24)12-19(13)20)6-9-21(4)18(16)7-10-22(21,25)14(2)23/h11-12,16-18,25H,5-10H2,1-4H3/t16-,17+,18+,20-,21+,22+/m1/s1
InChIKey
VXIMPSPISRVBPZ-NWUMPJBXSA-N
Cross-matching ID
PubChem CID
19090
CAS Number
3562-63-8
TTD ID
D04GJN
INTEDE ID
DR1017
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Progesterone receptor (PGR) TTUV8G9 PRGR_HUMAN Binder [5]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4)
Main DME 		DE4LYSA CP3A4_HUMAN Substrate [6]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Clusterin (CLU) OTQGG0JM CLUS_HUMAN Gene/Protein Processing [7]
Galanin peptides (GAL) OTB3VPTO GALA_HUMAN Gene/Protein Processing [7]
Metalloproteinase inhibitor 1 (TIMP1) OTOXC51H TIMP1_HUMAN Gene/Protein Processing [7]
Neuromodulin (GAP43) OT2OTGGV NEUM_HUMAN Gene/Protein Processing [7]
Nuclear receptor subfamily 1 group I member 2 (NR1I2) OTC5U0N5 NR1I2_HUMAN Gene/Protein Processing [8]
Proto-oncogene tyrosine-protein kinase receptor Ret (RET) OTLU040A RET_HUMAN Gene/Protein Processing [7]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Breast cancer
ICD Disease Classification 2C60-2C65
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Progesterone receptor (PGR) DTT PGR 3.26E-38 -3.79 -2.5
Cytochrome P450 3A4 (CYP3A4) DME CYP3A4 2.20E-02 -1.08E-01 -2.31E-01
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 Hormonal therapy in epithelial ovarian cancer. Expert Rev Anticancer Ther. 2006 Jan;6(1):43-7.
2 BDDCS applied to over 900 drugs
3 Critical Evaluation of Human Oral Bioavailability for Pharmaceutical Drugs by Using Various Cheminformatics Approaches
4 Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
5 Focus on anastrozole and breast cancer. Curr Med Res Opin. 2003;19(8):683-8.
6 Metabolism of megestrol acetate in vitro and the role of oxidative metabolites. Xenobiotica. 2018 Oct;48(10):973-983.
7 Discovery of molecular mechanisms of neuroprotection using cell-based bioassays and oligonucleotide arrays. Physiol Genomics. 2002 Oct 29;11(2):45-52. doi: 10.1152/physiolgenomics.00064.2002.
8 Identification and validation of novel human pregnane X receptor activators among prescribed drugs via ligand-based virtual screening. Drug Metab Dispos. 2011 Feb;39(2):337-44. doi: 10.1124/dmd.110.035808. Epub 2010 Nov 10.