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]
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Therapeutic Class

Anticancer 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)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

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)

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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]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)_{Main DME}	DE4LYSA	CP3A4_HUMAN	Substrate	[6]

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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]

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Molecular Interaction Atlas (MIA)

MIA Detail

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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)

MEA Detail

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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.