Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMNF38S)

• Drug Name: 16,16-dimethyl-PGE2 Drug Info
• Synonyms: 16,16-dimethylprostaglandin E2

Indication

Disease Entry	ICD 11	Status	REF
Stem cell engraftment	QB63.8	Phase 2	[1]

• Cross-matching ID:
  PubChem CID: 5283066
  ChEBI ID: CHEBI:141046
  CAS Number: CAS 39746-25-3
  TTD Drug ID: DMNF38S

Molecule-Related Drug Atlas

Drug(s) Targeting Prostaglandin E2 receptor EP4 (PTGER4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
RQ-00000007 (oral)	DMMYTRU	Pain	MG30-MG3Z	Phase 2	[5]
ONO-AE1-437	DMCUGI8	Asthma	CA23	Phase 2	[6]
BGC-20-1531	DMS2MQ5	Migraine	8A80	Phase 2	[7]
IK-007	DMBLFPN	Non-small-cell lung cancer	2C25	Phase 1/2	[8]
TPST-1495	DM3GSB2	Solid tumour/cancer	2A00-2F9Z	Phase 1	[9]
E7046	DMFVT43	Rectal adenocarcinoma	2B92	Phase 1	[10]
ONO-4232	DMO4SD2	Acute heart failure	BD10-BD13	Phase 1	[11]
ONO-4578	DME63VK	Solid tumour/cancer	2A00-2F9Z	Phase 1	[10]
AN0025	DMGSYPY	Aggressive cancer	2A00-2F9Z	Phase 1	[12]
PGF2alpha	DM4XAU7	Solid tumour/cancer	2A00-2F9Z	Clinical trial	[13]

Drug(s) Targeting Prostaglandin E2 receptor EP2 (PTGER2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dinoprostone	DMTYOPD	Medical abortion	JA00.1Z	Approved	[14]
Mycophenolate mofetil	DMPQAGE	Hepatosplenic T-cell lymphoma		Approved	[15]
Alprostadil	DMWH7NQ	Aorta coarctation		Approved	[16]
Iloprost	DMVPZBE	Pulmonary arterial hypertension	BB01.0	Approved	[17]
Omidenepag isopropyl	DMUX7Z8	Glaucoma/ocular hypertension	9C61	Approved	[18]
LAROPIPRANT	DM5FABJ	Coronary heart disease	BA80.Z	Phase 4	[19]
CP-533536	DMZEJLB	Osteoporosis	FB83.0	Phase 2	[20]
Taprenepag	DM1TSHL	Glaucoma/ocular hypertension	9C61	Phase 2	[21]
TPST-1495	DM3GSB2	Solid tumour/cancer	2A00-2F9Z	Phase 1	[9]
PF-4418948	DMMETU8	Endometriosis	GA10	Phase 1	[14]

Drug(s) Targeting Prostaglandin E2 receptor EP3 (PTGER3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ONO-9054	DM5O6GC	Glaucoma/ocular hypertension	9C61	Phase 2	[22]
PGF2alpha	DM4XAU7	Solid tumour/cancer	2A00-2F9Z	Clinical trial	[2]
BUTAPROST	DMVYNJZ	Discovery agent	N.A.	Patented	[14]
DG041	DMVO9WM	Peripheral vascular disease	BD4Z	Discontinued in Phase 2	[23]
GR-63799X	DM13GK8	Asthma	CA23	Discontinued in Phase 1	[24]
U46619	DM13FX4	Discovery agent	N.A.	Investigative	[25]
carbacyclin	DMMBQYE	Discovery agent	N.A.	Investigative	[2]
PGD2	DMYDW6J	Discovery agent	N.A.	Investigative	[13]
butaprost (free acid form)	DM5MZHP	Discovery agent	N.A.	Investigative	[25]
M&B 28767	DMJQG82	Discovery agent	N.A.	Investigative	[2]

Drug(s) Affected By Prostaglandin G/H synthase 2 (PTGS2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Eicosapentaenoic acid/docosa-hexaenoic acid	DMMUCG4	Hypertriglyceridemia	5C80.1	Approved	[26]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[27]
Gamolenic acid	DMQN30Z	Allergy	4A80-4A85	Approved	[28]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[29]
Flupentixol	DM0DJ9O	Schizophrenia	6A20	Approved	[30]
Sertraline	DM0FB1J	Coronary heart disease	BA80.Z	Approved	[31]
Ibandronate	DM0QZBN	Hypercalcaemia	5B91.0	Approved	[32]
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[33]
Fexofenadine	DM17ONX	Allergic rhinitis	CA08.0	Approved	[34]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[35]

Drug(s) Affected By 15-hydroxyprostaglandin dehydrogenase (HPGD)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[36]
Rofecoxib	DM3P5DA	Osteoarthritis	FA00-FA05	Approved	[37]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[38]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[39]
Testosterone	DM7HUNW	Hot flushes	GA30	Approved	[40]
Ibuprofen	DM8VCBE	Dysmenorrhea	GA34.3	Approved	[41]
Calcitriol	DM8ZVJ7	Congenital alopecia	LC30	Approved	[40]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[42]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[43]
Flurbiprofen	DMGN4BY	Osteoarthritis	FA00-FA05	Approved	[41]

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	Agonist	[2]
Prostaglandin E2 receptor EP3 (PTGER3)	TTPNGDE	PE2R3_HUMAN	Agonist	[2]
Prostaglandin E2 receptor EP4 (PTGER4)	TT79WV3	PE2R4_HUMAN	Agonist	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
15-hydroxyprostaglandin dehydrogenase (HPGD)	OTYZI6JB	PGDH_HUMAN	Gene/Protein Processing	[3]
Prostaglandin G/H synthase 2 (PTGS2)	OT75U9M4	PGH2_HUMAN	Gene/Protein Processing	[4]

References

• [1] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [2] 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.
• [3] Tumor growth inhibition by indomethacin in a mouse model of human medullary thyroid cancer: implication of cyclooxygenases and 15-hydroxyprostaglandin dehydrogenase. Endocrinology. 2004 May;145(5):2561-71. doi: 10.1210/en.2003-0915. Epub 2004 Jan 21.
• [4] Induction of cyclo-oxygenase-2 mRNA by prostaglandin E2 in human prostatic carcinoma cells. Br J Cancer. 1997;75(8):1111-8.
• [5] Clinical pipeline report, company report or official report of Avarx.
• [6] An EP4 receptor agonist prevents indomethacin-induced closure of rat ductus arteriosus in vivo. Pediatr Res. 2004 Oct;56(4):586-90.
• [7] BGC20-1531, a novel, potent and selective prostanoid EP4 receptor antagonist: a putative new treatment for migraine headache. Br J Pharmacol. 2009 January; 156(2): 316-327.
• [8] Grapiprant: an EP4 prostaglandin receptor antagonist and novel therapy for pain and inflammation. Vet Med Sci. 2015 Dec 21;2(1):3-9.
• [9] Clinical pipeline report, company report or official report of Tempest Therapeutics.
• [10] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [11] ONO-4232, an EP4-selective Agonist, Improves Left Ventricular Diastolic Dysfunction and Ameliorates Acute and Chronic Heart Failure in Animal Models. Circulation. 2012; 126: A15345.
• [12] AN0025, a novel antagonist of PGE2-receptor E-type 4 (EP4), in combination with total neoadjuvant treatment of advanced rectal cancer. Radiother Oncol. 2023 Aug;185:109669.
• [13] Molecular cloning and characterization of the four rat prostaglandin E2 prostanoid receptor subtypes. Eur J Pharmacol. 1997 Dec 11;340(2-3):227-41.
• [14] 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.
• [15] 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. (Target id: 341).
• [16] Emerging drugs for diabetic foot ulcers. Expert Opin Emerg Drugs. 2006 Nov;11(4):709-24.
• [17] Exploration of prostanoid receptor subtype regulating estradiol and prostaglandin E2 induction of spinophilin in developing preoptic area neurons. Neuroscience. 2007 May 25;146(3):1117-27.
• [18] Clinical pipeline report, company report or official report of Santen Pharmaceutical.
• [19] Discovery of a potent and selective prostaglandin D2 receptor antagonist, [(3R)-4-(4-chloro-benzyl)-7-fluoro-5-(methylsulfonyl)-1,2,3,4-tetrahydroc... J Med Chem. 2007 Feb 22;50(4):794-806.
• [20] Pfizer. Product Development Pipeline. March 31 2009.
• [21] A phase 2, randomized, dose-response trial of taprenepag isopropyl (PF-04217329) versus latanoprost 0.005% in open-angle glaucoma and ocular hypertension. Curr Eye Res. 2011 Sep;36(9):809-17.
• [22] IOP-Lowering Effect of ONO-9054, A Novel Dual Agonist of Prostanoid EP3 and FP Receptors, in Monkeys. Invest Ophthalmol Vis Sci. 2015 Apr;56(4):2547-52.
• [23] BAY x 1005 attenuates atherosclerosis in apoE/LDLR - double knockout mice. J Physiol Pharmacol. 2007 Sep;58(3):583-8.
• [24] Effects of the prostanoid EP3-receptor agonists M&B 28767 and GR 63799X on infarct size caused by regional myocardial ischaemia in the anaesthetized rat. Br J Pharmacol. 1999 Feb;126(4):849-58.
• [25] 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.
• [26] Docosahexaenoic acid regulates gene expression in HUVEC cells treated with polycyclic aromatic hydrocarbons. Toxicol Lett. 2015 Jul 16;236(2):75-81.
• [27] Etoposide induces necrosis through p53-mediated antiapoptosis in human kidney proximal tubule cells. Toxicol Sci. 2015 Nov;148(1):204-19.
• [28] Conjugated linoleic acid, unlike other unsaturated fatty acids, strongly induces glutathione synthesis without any lipoperoxidation. Br J Nutr. 2006 Nov;96(5):811-9.
• [29] COX-2 and PPAR-gama confer cannabidiol-induced apoptosis of human lung cancer cells. Mol Cancer Ther. 2013 Jan;12(1):69-82.
• [30] Mitochondrial involvement in schizophrenia and other functional psychoses. Neurochem Res. 1996 Sep;21(9):995-1004.
• [31] Immunomodulatory effect of selective serotonin reuptake inhibitors (SSRIs) on human T lymphocyte function and gene expression. Eur Neuropsychopharmacol. 2007 Dec;17(12):774-80.
• [32] Stimulation of cyclooxygenase-2 expression by bone-derived transforming growth factor-beta enhances bone metastases in breast cancer. Cancer Res. 2006 Feb 15;66(4):2067-73.
• [33] Arsenite and cadmium promote the development of mammary tumors. Carcinogenesis. 2020 Jul 14;41(7):1005-1014. doi: 10.1093/carcin/bgz176.
• [34] An in vitro coculture system of human peripheral blood mononuclear cells with hepatocellular carcinoma-derived cells for predicting drug-induced liver injury. Arch Toxicol. 2021 Jan;95(1):149-168. doi: 10.1007/s00204-020-02882-4. Epub 2020 Aug 20.
• [35] A2E selectively induces cox-2 in ARPE-19 and human neural cells. Curr Eye Res. 2006 Mar;31(3):259-63.
• [36] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [37] Rofecoxib modulates multiple gene expression pathways in a clinical model of acute inflammatory pain. Pain. 2007 Mar;128(1-2):136-47.
• [38] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [39] Global effects of inorganic arsenic on gene expression profile in human macrophages. Mol Immunol. 2009 Feb;46(4):649-56.
• [40] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [41] 15-Hydroxyprostaglandin dehydrogenase (15-PGDH) is up-regulated by flurbiprofen and other non-steroidal anti-inflammatory drugs in human colon cancer HT29 cells. Arch Biochem Biophys. 2009 Jul 15;487(2):139-45. doi: 10.1016/j.abb.2009.05.017. Epub 2009 Jun 6.
• [42] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [43] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.