Details of the Drug

General Information of Drug (ID: DMBGWPH)

Drug Name

Medroxyprogesterone

Synonyms

Asconale; Colirest; Hematrol; Hydroxymethylprogesterone; Lunelle; Medrossiprogesterone; Medroxiprogesterona; Medroxiprogesteronum; Medroxyprogesteron; Medroxyprogesteronum; Methylhydroxyprogesterone; Adgyn Medro; Farlutal inyectable; Medroprogesterone Acetate; Medrossiprogesterone [DCIT]; Medroxyprogesteron acetate; Medroxyprogesterone Strakan Brand; Sodelut G; Strakan Brand of Medroxyprogesterone; MPA Gyn 5; U 8840; CBP-1011; Farlutal inyectable (TN); G-Farlutal; Medroxiprogesterona [INN-Spanish]; Medroxyprogesterone (INN); Medroxyprogesterone [INN:BAN]; Medroxyprogesteronum [INN-Latin]; Novo-Medrone; Pregn-4-ene-3,20-dione, 17-hydroxy-6-methyl-, (6alpha)-(9CI); Pregn-4-ene-3,20-dione, 17-hydroxy-6-methyl-, (6-alpha)-(9CI); (6S,8R,9S,10R,13S,14S,17R)-17-acetyl-17-hydroxy-6,10,13-trimethyl-2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthren-3-one; (6alpha)-17-hydroxy-6-methylpregn-4-ene-3,20-dione; 17 alpha Hydroxy 6 alpha Methylprogesterone; 17 alpha-Hydroxy-6 alpha-Methylprogesterone; 17-Hydroxy-6.alpha.-methylprogesterone; 17-Hydroxy-6alpha-methyl-pregn-4-ene-3,20-dione; 17-Hydroxy-6alpha-methylprogesterone; 17.alpha.-Hydroxy-6.alpha.-methylprogesterone; 17alpha-Hydroxy-6alpha-methyl-4-pregnene-3,20-dione; 17alpha-Hydroxy-6alpha-methylprogesterone; 6-Dihydromegestrol; 6-alpha-Methyl-17-alpha-hydroxyprogesterone; 6.alpha.-Methyl-17.alpha.-hydroxyprogesterone; 6alpha-Methyl-17alpha-hydroxyprogesterone; 6alpha-Methyl-4-pregnen-17alpha-ol-3,20-dione; 6alpha-Methyl-5-pregnen-17alpha-ol-3,20-dione

Indication

Disease Entry	ICD 11	Status	REF
Solid tumour/cancer	2A00-2F9Z	Approved	[1]

Therapeutic Class

Contraceptive Agents

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

344.5

Topological Polar Surface Area (xlogp)

3.5

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]
Elimination: 44% 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 0.061 micromolar/kg/day [3]
Water Solubility: The ability of drug to dissolve in water is measured as 0.022 mg/mL [2]

Chemical Identifiers

Formula: C22H32O3
IUPAC Name: (6S,8R,9S,10R,13S,14S,17R)-17-acetyl-17-hydroxy-6,10,13-trimethyl-2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthren-3-one
Canonical SMILES: C[C@H]1C[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/C22H32O3/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/h12-13,16-18,25H,5-11H2,1-4H3/t13-,16+,17-,18-,20+,21-,22-/m0/s1
InChIKey: FRQMUZJSZHZSGN-HBNHAYAOSA-N

Cross-matching ID

PubChem CID: 10631
ChEBI ID: CHEBI:6715
CAS Number: 520-85-4
TTD ID: D0I2SD
INTEDE ID: DR1012

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Progesterone receptor (PGR)	TTUV8G9	PRGR_HUMAN	Agonist	[4]

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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	[5]

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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease

Solid tumour/cancer

ICD Disease Classification

2A00-2F9Z

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

Jump to Detail Molecular Expression Atlas of This Drug

References

1	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
2	BDDCS applied to over 900 drugs
3	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
4	Dienogest is a selective progesterone receptor agonist in transactivation analysis with potent oral endometrial activity due to its efficient pharm... Steroids. 2008 Feb;73(2):222-31.
5	Metabolic profiling and cytochrome P450 reaction phenotyping of medroxyprogesterone acetate. Drug Metab Dispos. 2008 Nov;36(11):2292-8.
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7	Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
8	Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75.
9	Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
10	Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
11	Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
12	Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
13	The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
14	Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
15	Clinical pipeline report, company report or official report of lipocine.
16	Preclinical experience with two selective progesterone receptor modulators on breast and endometrium. Steroids. 2000 Oct-Nov;65(10-11):733-40.
17	Mullard A: 2010 FDA drug approvals. Nat Rev Drug Discov. 2011 Feb;10(2):82-5.
18	Pharmacological profile of progestins. Maturitas. 2008 Sep-Oct;61(1-2):151-7.
19	Focus on anastrozole and breast cancer. Curr Med Res Opin. 2003;19(8):683-8.
20	2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
21	Contribution of functional groups of 19-nor-progestogens to binding to progesterone and estradiol-17beta receptors in rabbit uterus. Endocrinology. 1977 Jun;100(6):1579-84.