Details of the Drug

General Information of Drug (ID: DMTYOPD)

Drug Name
Dinoprostone
Synonyms
Cervidil; Dinoproston; Dinoprostona; Dinoprostonum; Prepidil; Propess; Prostenon; Prostin; Prepidil Gel; Prostarmon E;Prostin E; Dinoprostone Prostaglandin E2; Minprositin E2; Minprostin E2; PGE2; PGE2 alpha; PGE2alpha; Prostaglandin E2; Prostaglandin E2 alpha; Prostaglandin E2alpha; Prostarmon E2; Prostin E2; U 12062; [3H]PGE2; Alpha, PGE2; Alpha, Prostaglandin E2; BML1-F07; Cervidil (TN); Dinoprostona [INN-Spanish]; Dinoprostone beta-Cyclodextrin Clathrate; Dinoprostonum [INN-Latin]; E2 alpha, Prostaglandin; E2, Prostaglandin; E2alpha, Prostaglandin; Gel, Prepidil; L-PGE2; L-Prostaglandin E2; Prepidil (TN); Propess (TN); Prostin E2 (TN); U-12062; BMS-279654 & PGE2; Dinoprostone (JAN/USP/INN); Dinoprostone [USAN:INN:BAN:JAN]; L-7-(3-Hydroxy-2-(3-hydroxy-1-octenyl)-5-oxocyclopentyl)-5-heptenoic acid; (15S)-Prostaglandin E2; (5Z,11-alpha,13E,15S)-11,15-Dihydroxy-9-oxoprosta-5,13-dien-1-oic acid; (5Z,11.alpha.,13E,15S)-11,15-Dihydroxy-9-oxoprosta-5,13-dien-1-oic acid; (5Z,11alpha,13E,15S)-11,15-Dihydroxy-9-oxoprosta-5,13-dien-1-oic; (5Z,11alpha,13E,15S)-11,15-Dihydroxy-9-oxoprosta-5,13-dienoic acid; (5Z,11alpha,13E,15S)-11,15-dihydroxy-9-oxoprosta-5,13-dien-1-oic acid; (5Z,13E)-(15S)-11alpha,15-Dihydroxy-9-oxoprost-13-enoate; (5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprosta-5,13-dienoate; (5Z,13E,15S)-11alpha,15-dihydroxy-9-oxoprosta-5,13-dien-1-oic acid; (E,Z)-(1R,2R,3R)-7-(3-Hydroxy-2-((3S)-(3-hydroxy-1-octenyl))-5-oxocyclopentyl)-5-heptenoic acid; (Z)-7-[(1R,2R,3R)-3-Hydroxy-2-[(E,3S)-3-hydroxyoct-1-enyl]-5-oxocyclopentyl]hept-5-enoic acid; 5-Heptenoic acid, 7-(3-hydroxy-2-(3-hydroxy-1-octenyl)-5-oxocyclopentyl)-(8CI); 7-(3-Hydroxy-2-(3-hydroxy-1-octenyl)-5-oxocyclopentyl)-5-heptenoic acid
Indication
Disease Entry ICD 11 Status REF
Medical abortion JA00.1Z Approved [1]
Therapeutic Class
Prostaglandins
Affected Organisms
Humans and other mammals
ATC Code
G02AD02: Dinoprostone
G02AD: Prostaglandins
G02A: UTEROTONICS
G02: OTHER GYNECOLOGICALS
G: GENITO URINARY SYSTEM AND SEX HORMONES
G02AD02: Dinoprostone
G02AD: Prostaglandins
G02A: UTEROTONICS
G02: OTHER GYNECOLOGICALS
G: GENITO URINARY SYSTEM AND SEX HORMONES
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 1 Molecular Weight (mw) 352.5
Logarithm of the Partition Coefficient (xlogp) 2.8
Rotatable Bond Count (rotbonds) 12
Hydrogen Bond Donor Count (hbonddonor) 3
Hydrogen Bond Acceptor Count (hbondacc) 5
ADMET Property
Half-life
The concentration or amount of drug in body reduced by one-half in less than 5 minutes [2]
Metabolism
The drug is metabolized via the lung []
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 4.053 micromolar/kg/day [3]
Chemical Identifiers
Formula
C20H32O5
IUPAC Name
(Z)-7-[(1R,2R,3R)-3-hydroxy-2-[(E,3S)-3-hydroxyoct-1-enyl]-5-oxocyclopentyl]hept-5-enoic acid
Canonical SMILES
CCCCC[C@@H](/C=C/[C@H]1[C@@H](CC(=O)[C@@H]1C/C=C\\CCCC(=O)O)O)O
InChI
InChI=1S/C20H32O5/c1-2-3-6-9-15(21)12-13-17-16(18(22)14-19(17)23)10-7-4-5-8-11-20(24)25/h4,7,12-13,15-17,19,21,23H,2-3,5-6,8-11,14H2,1H3,(H,24,25)/b7-4-,13-12+/t15-,16+,17+,19+/m0/s1
InChIKey
XEYBRNLFEZDVAW-ARSRFYASSA-N
Cross-matching ID
PubChem CID
5280360
ChEBI ID
CHEMBL548
CAS Number
363-24-6
UNII
K7Q1JQR04M
DrugBank ID
DB00917
TTD ID
D06FEA
VARIDT ID
DR00102
INTEDE ID
DR0511
ACDINA ID
D01006
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
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug
Repurposed Drugs (RPD) Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Prostaglandin E2 receptor EP2 (PTGER2) TT1ZAVI PE2R2_HUMAN Antagonist [4]
Prostaglandin F2-alpha receptor (PTGFR) TTT2ZAR PF2R_HUMAN Antagonist [4]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
Organic anion transporting polypeptide 5A1 (SLCO5A1) DTYVQ5M SO5A1_HUMAN Substrate [5]
Organic anion transporting polypeptide 2A1 (SLCO2A1) DT021JD SO2A1_HUMAN Substrate [6]
Organic solute transporter subunit alpha (SLC51A) DTMEQ32 OSTA_HUMAN Substrate [7]
Organic anion transporting polypeptide 1C1 (SLCO1C1) DTPYCQ4 SO1C1_HUMAN Substrate [8]
Organic anion transporting polypeptide 3A1 (SLCO3A1) DTVNRXW SO3A1_HUMAN Substrate [9]
Organic solute transporter subunit beta (SLC51B) DT1V9AJ OSTB_HUMAN Substrate [7]
Organic anion transporting polypeptide 4A1 (SLCO4A1) DT8H2IC SO4A1_HUMAN Substrate [6]
Organic anion transporter 2 (SLC22A7) DT0OC1Q S22A7_HUMAN Substrate [10]
Multidrug resistance-associated protein 2 (ABCC2) DTFI42L MRP2_HUMAN Substrate [11]
Organic anion transporter 4 (SLC22A11) DT06JWZ S22AB_HUMAN Substrate [10]
Multidrug resistance-associated protein 4 (ABCC4) DTCSGPB MRP4_HUMAN Substrate [12]
Organic cation transporter 1 (SLC22A1) DTT79CX S22A1_HUMAN Substrate [13]
Organic anion transporting polypeptide 2B1 (SLCO2B1) DTPFTEQ SO2B1_HUMAN Substrate [6]
Organic anion transporting polypeptide 1A2 (SLCO1A2) DTE2B1D SO1A2_HUMAN Substrate [14]
Organic anion transporter 1 (SLC22A6) DTQ23VB S22A6_HUMAN Substrate [10]
Organic anion transporting polypeptide 1B1 (SLCO1B1) DT3D8F0 SO1B1_HUMAN Substrate [15]
Organic cation transporter 2 (SLC22A2) DT9IDPW S22A2_HUMAN Substrate [13]
Organic anion transporter 3 (SLC22A8) DTVP67E S22A8_HUMAN Substrate [10]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Substrate [16]
Cytochrome P450 4F2 (CYP4F2) DE3GT9C CP4F2_HUMAN Substrate [17]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
15-hydroxyprostaglandin dehydrogenase (HPGD) OTYZI6JB PGDH_HUMAN Regulation of Drug Effects [18]
3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 2 (HSD3B2) OT02MSKN 3BHS2_HUMAN Gene/Protein Processing [19]
Actin, aortic smooth muscle (ACTA2) OTEDLG8E ACTA_HUMAN Gene/Protein Processing [20]
Amyloid-beta precursor protein (APP) OTKFD7R4 A4_HUMAN Regulation of Drug Effects [21]
Baculoviral IAP repeat-containing protein 3 (BIRC3) OT3E95KB BIRC3_HUMAN Gene/Protein Processing [22]
C-C motif chemokine 2 (CCL2) OTAD2HEL CCL2_HUMAN Gene/Protein Processing [23]
C-C motif chemokine 22 (CCL22) OTT3QJC2 CCL22_HUMAN Gene/Protein Processing [23]
C-C motif chemokine 3 (CCL3) OTW2H3ND CCL3_HUMAN Gene/Protein Processing [23]
C-C motif chemokine 4 (CCL4) OT6B8P25 CCL4_HUMAN Gene/Protein Processing [23]
C-C motif chemokine 5 (CCL5) OTSCA5CK CCL5_HUMAN Gene/Protein Processing [23]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Medical abortion
ICD Disease Classification JA00.1Z
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Prostaglandin F2-alpha receptor (PTGFR) DTT PTGFR 8.25E-02 -0.05 -0.14
Organic anion transporting polypeptide 5A1 (SLCO5A1) DTP OATP5A1 2.97E-02 -4.05E-02 -2.68E-01
Organic anion transporter 3 (SLC22A8) DTP OAT3 5.19E-01 -8.88E-03 -2.08E-02
Organic anion transporting polypeptide 3A1 (SLCO3A1) DTP OATP3A1 1.83E-05 3.48E-01 6.12E-01
Organic cation transporter 1 (SLC22A1) DTP SLC22A1 8.54E-01 1.24E-02 7.20E-02
Organic anion transporter 1 (SLC22A6) DTP OAT1 7.18E-01 -4.56E-02 -1.42E-01
Organic anion transporting polypeptide 1C1 (SLCO1C1) DTP OATP1C1 2.92E-03 1.25E-01 2.35E-01
Organic anion transporting polypeptide 2B1 (SLCO2B1) DTP OATP2B1 6.30E-05 2.52E-01 5.88E-01
Organic solute transporter subunit alpha (SLC51A) DTP OSTalpha 8.72E-01 2.36E-03 1.33E-02
Multidrug resistance-associated protein 2 (ABCC2) DTP MRP2 7.16E-01 -1.28E-02 -6.06E-02
Organic anion transporting polypeptide 1A2 (SLCO1A2) DTP OATP1A2 1.16E-03 4.00E-01 4.43E-01
Multidrug resistance-associated protein 4 (ABCC4) DTP MRP4 3.73E-06 2.82E-01 7.01E-01
Organic cation transporter 2 (SLC22A2) DTP SLC22A2 8.22E-01 -1.05E-02 -3.83E-02
Organic anion transporting polypeptide 4A1 (SLCO4A1) DTP OATP4A1 6.12E-05 4.04E-01 8.66E-01
Organic anion transporting polypeptide 1B1 (SLCO1B1) DTP OATP1B1 8.15E-01 6.20E-03 5.61E-02
Organic solute transporter subunit beta (SLC51B) DTP OSTbeta 5.98E-01 3.62E-02 2.04E-01
Organic anion transporter 2 (SLC22A7) DTP OAT2 5.96E-02 -5.09E-02 -3.48E-01
Organic anion transporter 4 (SLC22A11) DTP OAT4 4.61E-04 -7.04E-02 -3.49E-01
Organic anion transporting polypeptide 2A1 (SLCO2A1) DTP OATP2A1 3.03E-03 -9.85E-02 -3.19E-01
Cytochrome P450 1A2 (CYP1A2) DME CYP1A2 7.36E-01 1.62E-02 1.08E-01
Cytochrome P450 4F2 (CYP4F2) DME CYP4F2 2.43E-02 2.94E-02 1.61E-01
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG
DIG Name DIG ID PubChem CID Functional Classification
Polyethylene glycol 4000 E00654 Not Available Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Triacetin E00080 5541 Humectant; Plasticizing agent; Solvent
Hydrophobic colloidal silica E00285 24261 Anticaking agent; Emulsion stabilizing agent; Glidant; Suspending agent; Viscosity-controlling agent
Pharmaceutical Formulation
Formulation Name Drug Dosage Dosage Form Route
Dinoprostone 10mg extended release insert 10mg Extended Release Insert Vaginal
Dinoprostone 0.5mg/3gm gel 0.5mg/3gm Gel Endocervical
Jump to Detail Pharmaceutical Formulation Page of This Drug

References

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: 1916).
2 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
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 Evaluation of WO 2012/177618 A1 and US-2014/0179750 A1: novel small molecule antagonists of prostaglandin-E2 receptor EP2.Expert Opin Ther Pat. 2015 Jul;25(7):837-44.
5 Expression and regulation of prostaglandin transporters, ATP-binding cassette, subfamily C, member 1 and 9, and solute carrier organic anion transporter family, member 2A1 and 5A1 in the uterine endometrium during the estrous cycle and pregnancy in pigs. Asian-Australas J Anim Sci. 2017 May;30(5):643-652.
6 Molecular identification and characterization of novel members of the human organic anion transporter (OATP) family. Biochem Biophys Res Commun. 2000 Jun 24;273(1):251-60.
7 Functional complementation between a novel mammalian polygenic transport complex and an evolutionarily ancient organic solute transporter, OSTalpha-OSTbeta. J Biol Chem. 2003 Jul 25;278(30):27473-82.
8 Identification of a novel human organic anion transporting polypeptide as a high affinity thyroxine transporter. Mol Endocrinol. 2002 Oct;16(10):2283-96.
9 Molecular characterization of human and rat organic anion transporter OATP-D. Am J Physiol Renal Physiol. 2003 Dec;285(6):F1188-97.
10 Human organic anion transporters and human organic cation transporters mediate renal transport of prostaglandins. J Pharmacol Exp Ther. 2002 Apr;301(1):293-8.
11 Multidrug resistance associated protein 2 mediates transport of prostaglandin E2. Liver Int. 2006 Apr;26(3):362-8.
12 The human multidrug resistance protein MRP4 functions as a prostaglandin efflux transporter and is inhibited by nonsteroidal antiinflammatory drugs. Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9244-9.
13 Are organic cation transporters capable of transporting prostaglandins? Naunyn Schmiedebergs Arch Pharmacol. 2005 Aug;372(2):125-30.
14 Localization of organic anion transporting polypeptide 4 (Oatp4) in rat liver and comparison of its substrate specificity with Oatp1, Oatp2 and Oatp3. Pflugers Arch. 2001 Nov;443(2):188-95.
15 Organic anion transporting polypeptide 1B1: a genetically polymorphic transporter of major importance for hepatic drug uptake. Pharmacol Rev. 2011 Mar;63(1):157-81.
16 Effects of polyunsaturated fatty acids on prostaglandin synthesis and cyclooxygenase-mediated DNA adduct formation by heterocyclic aromatic amines in human adenocarcinoma colon cells. Mol Carcinog. 2004 Jul;40(3):180-8.
17 Cloning and characterization of CYP4F21: a prostaglandin E2 20-hydroxylase of ram seminal vesicles. Arch Biochem Biophys. 2001 May 1;389(1):123-9.
18 Mutations in 15-hydroxyprostaglandin dehydrogenase cause primary hypertrophic osteoarthropathy. Nat Genet. 2008 Jun;40(6):789-93. doi: 10.1038/ng.153. Epub 2008 May 25.
19 Prostaglandin E2 via steroidogenic factor-1 coordinately regulates transcription of steroidogenic genes necessary for estrogen synthesis in endometriosis. J Clin Endocrinol Metab. 2009 Feb;94(2):623-31.
20 Aryl hydrocarbon receptor-ligand axis mediates pulmonary fibroblast migration and differentiation through increased arachidonic acid metabolism. Toxicology. 2016 Aug 31;370:116-126.
21 Amyloid proteotoxicity initiates an inflammatory response blocked by cannabinoids. NPJ Aging Mech Dis. 2016 Jun 23;2:16012. doi: 10.1038/npjamd.2016.12. eCollection 2016.
22 Inhibition of apoptosis in normal and transformed intestinal epithelial cells by cAMP through induction of inhibitor of apoptosis protein (IAP)-2. Proc Natl Acad Sci U S A. 2003 Jul 22;100(15):8921-6. doi: 10.1073/pnas.1533221100. Epub 2003 Jul 1.
23 Maturation of human monocyte-derived dendritic cells (MoDCs) in the presence of prostaglandin E2 optimizes CD4 and CD8 T cell-mediated responses to protein antigens: role of PGE2 in chemokine and cytokine expression by MoDCs. Int Immunol. 2005 Dec;17(12):1561-72. doi: 10.1093/intimm/dxh335. Epub 2005 Nov 22.