Details of the Drug

General Information of Drug (ID: DM4XAU7)

Drug Name
PGF2alpha
Synonyms Amoglandin; Cerviprost; Cyclosin; Enzaprost; Panacelan; prostaglandin F2alpha
Indication
Disease Entry ICD 11 Status REF
Solid tumour/cancer 2A00-2F9Z Clinical trial [1]
Drug Type
Small molecular drug
Structure
3D MOL is unavailable 2D MOL
#Ro5 Violations (Lipinski): 1 Molecular Weight (mw) 354.5
Logarithm of the Partition Coefficient (xlogp) 2.7
Rotatable Bond Count (rotbonds) 12
Hydrogen Bond Donor Count (hbonddonor) 4
Hydrogen Bond Acceptor Count (hbondacc) 5
Chemical Identifiers
Formula
C20H34O5
IUPAC Name
(Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(E,3S)-3-hydroxyoct-1-enyl]cyclopentyl]hept-5-enoic acid
Canonical SMILES
CCCCC[C@@H](/C=C/[C@H]1[C@@H](C[C@@H]([C@@H]1C/C=C\\CCCC(=O)O)O)O)O
InChI
InChI=1S/C20H34O5/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/h4,7,12-13,15-19,21-23H,2-3,5-6,8-11,14H2,1H3,(H,24,25)/b7-4-,13-12+/t15-,16+,17+,18-,19+/m0/s1
InChIKey
PXGPLTODNUVGFL-YNNPMVKQSA-N
Cross-matching ID
PubChem CID
5280363
ChEBI ID
CHEBI:15553
CAS Number
551-11-1
DrugBank ID
DB12789
TTD ID
D00HTY
VARIDT ID
DR00007
INTEDE ID
DR1917

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Prostaglandin D2 receptor (PTGDR) TTNVEIR PD2R_HUMAN Agonist [2]
Prostaglandin D2 receptor 2 (PTGDR2) TTQDMX5 PD2R2_HUMAN Agonist [3]
Prostaglandin E2 receptor EP1 (PTGER1) TTG1QMU PE2R1_HUMAN Agonist [4]
Prostaglandin E2 receptor EP2 (PTGER2) TT1ZAVI PE2R2_HUMAN Agonist [5]
Prostaglandin E2 receptor EP3 (PTGER3) TTPNGDE PE2R3_HUMAN Agonist [6]
Prostaglandin E2 receptor EP4 (PTGER4) TT79WV3 PE2R4_HUMAN Agonist [4]
Prostaglandin F2-alpha receptor (PTGFR) TTT2ZAR PF2R_HUMAN Agonist [7]
Thromboxane A2 receptor (TBXA2R) TT2O84V TA2R_HUMAN Agonist [2]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
Organic anion transporting polypeptide 2A1 (SLCO2A1) DT021JD SO2A1_HUMAN Substrate [8]
Organic anion transporting polypeptide 3A1 (SLCO3A1) DTVNRXW SO3A1_HUMAN Substrate [9]
Organic anion transporter 2 (SLC22A7) DT0OC1Q S22A7_HUMAN Substrate [10]
Organic anion transporter 4 (SLC22A11) DT06JWZ S22AB_HUMAN Substrate [11]
Multidrug resistance-associated protein 4 (ABCC4) DTCSGPB MRP4_HUMAN Substrate [12]
Organic cation transporter 1 (SLC22A1) DTT79CX S22A1_HUMAN Substrate [11]
Organic anion transporter 1 (SLC22A6) DTQ23VB S22A6_HUMAN Substrate [11]
Organic cation transporter 2 (SLC22A2) DT9IDPW S22A2_HUMAN Substrate [11]
Organic anion transporter 3 (SLC22A8) DTVP67E S22A8_HUMAN Substrate [11]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
NADPH-dependent carbonyl reductase 1 (CBR1)
Main DME 		DE9JFMC CBR1_HUMAN Substrate [13]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2) OTHF4H9U DHI2_HUMAN Gene/Protein Processing [14]
Acyl-protein thioesterase 2 (LYPLA2) OT03UIYC LYPA2_HUMAN Biotransformations [15]
Aldo-keto reductase family 1 member C2 (AKR1C2) OTQ2XMO3 AK1C2_HUMAN Regulation of Drug Effects [16]
Choriogonadotropin subunit beta 3 (CGB3) OTVM2SU3 CGB3_HUMAN Biotransformations [17]
Cocaine esterase (CES2) OTC647SQ EST2_HUMAN Biotransformations [18]
Interleukin-1 alpha (IL1A) OTPSGILV IL1A_HUMAN Regulation of Drug Effects [19]
Interleukin-1 beta (IL1B) OT0DWXXB IL1B_HUMAN Regulation of Drug Effects [20]
Interleukin-10 (IL10) OTIRFRXC IL10_HUMAN Regulation of Drug Effects [20]
Interleukin-4 (IL4) OTOXBWAU IL4_HUMAN Regulation of Drug Effects [21]
Liver carboxylesterase 1 (CES1) OT9L0LR8 EST1_HUMAN Biotransformations [18]
Molecular Interaction Atlas (MIA) 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
Prostaglandin F2-alpha receptor (PTGFR) DTT PTGFR 8.25E-02 -0.05 -0.14
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
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 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
NADPH-dependent carbonyl reductase 1 (CBR1) DME CBR1 3.47E-01 1.55E-01 2.60E-01
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 Stereocontrolled organocatalytic synthesis of prostaglandin PGF2alpha in seven steps. Nature. 2012 Sep 13;489(7415):278-81.
2 The utilization of recombinant prostanoid receptors to determine the affinities and selectivities of prostaglandins and related analogs. Biochim Biophys Acta. 2000 Jan 17;1483(2):285-93.
3 Expression and molecular pharmacology of the mouse CRTH2 receptor. J Pharmacol Exp Ther. 2003 Aug;306(2):463-70.
4 Molecular cloning and characterization of the four rat prostaglandin E2 prostanoid receptor subtypes. Eur J Pharmacol. 1997 Dec 11;340(2-3):227-41.
5 Importance of the extracellular domain for prostaglandin EP(2) receptor function. Mol Pharmacol. 1999 Sep;56(3):545-51.
6 Ligand binding specificities of the eight types and subtypes of the mouse prostanoid receptors expressed in Chinese hamster ovary cells. Br J Pharmacol. 1997 Sep;122(2):217-24.
7 Identification by site-directed mutagenesis of amino acids contributing to ligand-binding specificity or signal transduction properties of the human FP prostanoid receptor. Biochem J. 2003 Apr 15;371(Pt 2):443-9.
8 Cloning, in vitro expression, and tissue distribution of a human prostaglandin transporter cDNA(hPGT). J Clin Invest. 1996 Sep 1;98(5):1142-9.
9 Molecular characterization of human and rat organic anion transporter OATP-D. Am J Physiol Renal Physiol. 2003 Dec;285(6):F1188-97.
10 Interaction of human organic anion transporters 2 and 4 with organic anion transport inhibitors. J Pharmacol Exp Ther. 2002 Jun;301(3):797-802.
11 Human organic anion transporters and human organic cation transporters mediate renal transport of prostaglandins. J Pharmacol Exp Ther. 2002 Apr;301(1):293-8.
12 Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
13 Metabolism of prostaglandins by the nonpregnant human uterus. J Clin Endocrinol Metab. 1983 Apr;56(4):678-85.
14 Prostaglandins and leukotriene B4 are potent inhibitors of 11beta-hydroxysteroid dehydrogenase type 2 activity in human choriocarcinoma JEG-3 cells. Biol Reprod. 1999 Jul;61(1):40-5.
15 Identification of the major prostaglandin glycerol ester hydrolase in human cancer cells. J Biol Chem. 2014 Dec 5;289(49):33741-53. doi: 10.1074/jbc.M114.582353. Epub 2014 Oct 9.
16 Relationship of human liver dihydrodiol dehydrogenases to hepatic bile-acid-binding protein and an oxidoreductase of human colon cells. Biochem J. 1996 Jan 15;313 ( Pt 2)(Pt 2):373-6.
17 Expression of cyclooxygenase genes and production of prostaglandins during ovulation in the ovarian follicles of Xenopus laevis. Gen Comp Endocrinol. 2008 Jun;157(2):165-73. doi: 10.1016/j.ygcen.2008.04.012. Epub 2008 May 1.
18 Inactivation of lipid glyceryl ester metabolism in human THP1 monocytes/macrophages by activated organophosphorus insecticides: role of carboxylesterases 1 and 2. Chem Res Toxicol. 2010 Dec 20;23(12):1890-904. doi: 10.1021/tx1002194.
19 Effects of PCB126 and 17beta-oestradiol on endothelium-derived vasoactive factors in human endothelial cells. Toxicology. 2011 Jul 11;285(1-2):46-56.
20 Dexamethasone or interleukin-10 blocks interleukin-1beta-induced uterine contractions in pregnant rhesus monkeys. Am J Obstet Gynecol. 2003 Jan;188(1):252-63. doi: 10.1067/mob.2003.70.
21 Suppressive effects of antimycotics on thymic stromal lymphopoietin production in human keratinocytes. J Dermatol Sci. 2013 Sep;71(3):174-83. doi: 10.1016/j.jdermsci.2013.04.023. Epub 2013 May 2.