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
• ATC Code:
  G03AC06: Medroxyprogesterone
  G03AC: Progestogens
  G03A: HORMONAL CONTRACEPTIVES FOR SYSTEMIC USE
  G03: SEX HORMONES AND MODULATORS OF THE GENITAL SYSTEM
  G: GENITO URINARY SYSTEM AND SEX HORMONES
  G03DA02: Medroxyprogesterone
  G03DA: Pregnen (4) derivatives
  G03D: PROGESTOGENS
  G03: SEX HORMONES AND MODULATORS OF THE GENITAL SYSTEM
  G: GENITO URINARY SYSTEM AND SEX HORMONES
  G03DA02: Medroxyprogesterone
  G03DA: Pregnen (4) derivatives
  G03D: PROGESTOGENS
  G03: SEX HORMONES AND MODULATORS OF THE GENITAL SYSTEM
  G: GENITO URINARY SYSTEM AND SEX HORMONES
  L02AB02: Medroxyprogesterone
  L02AB: Progestogens
  L02A: HORMONES AND RELATED AGENTS
  L02: ENDOCRINE THERAPY
  L: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
  L02AB02: Medroxyprogesterone
  L02AB: Progestogens
  L02A: HORMONES AND RELATED AGENTS
  L02: ENDOCRINE THERAPY
  L: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 344.5
  Logarithm of the Partition Coefficient (xlogp); 3.5
  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]
  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]

Adverse Drug Reaction (ADR)

ADR Term	Variation	Related DOT	DOT ID	REF
Breast cancer	Not Available	mpra	OTEUBPKL	[4]

• 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: CHEMBL1390
  CAS Number: 520-85-4
  TTD ID: D0I2SD
  INTEDE ID: DR1012
• Drug-Molecule Activity Atlas (DMA)NEW: Click to Jump to the Detailed DMA Information of This Drug
• Drug Pharmacogenomic Perturbation (DPP)NEW: Click to Jump to the Detailed DPP Information of This Drug
• Drug ADMET Endpoint Profile (DAE)NEW: Click to Jump to the Detailed DAE 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	Agonist	[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
Membrane progestin receptor alpha (mpra)	OTEUBPKL	MPRA_CYNNE	Drug Response	[4]

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

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] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
• [5] 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.
• [6] Metabolic profiling and cytochrome P450 reaction phenotyping of medroxyprogesterone acetate. Drug Metab Dispos. 2008 Nov;36(11):2292-8.