Overview on the Discovery and Development of Anti-Inflammatory Drugs: Should the Focus Be on Synthesis or Degradation of PGE₂?

References

• Inoue H, Tanabe T, Umesono K. Feedback control of cyclooxygenase-2 expression through PPARgamma. J Biol Chem. 2000;275(36):28028–28032. doi:10.1074/jbc.M001387200
   PubMed Web of Science ®Google Scholar
• Newton R, Kuitert LM, Bergmann M, Adcock IM, Barnes PJ. Evidence for involvement of NF-kappaB in the transcriptional control of COX-2 gene expression by IL-1beta. Biochem Biophys Res Commun. 1997;237(1):28–32. doi:10.1006/bbrc.1997.7064
   PubMed Web of Science ®Google Scholar
• Korbecki J, Baranowska-Bosiacka I, Gutowska I, Piotrowska K, Chlubek D. Cyclooxygenase-1 as the main source of proinflammatory factors after sodium orthovanadate treatment. Biol Trace Elem Res. 2015;163(1–2):103–111. doi:10.1007/s12011-014-0176-4
   PubMed Web of Science ®Google Scholar
• Olszowski T, Gutowska I, Baranowska-Bosiacka I, et al. The effect of Cadmium on COX-1 and COX-2 gene, protein expression, and enzymatic activity in THP-1 macrophages. Biol Trace Elem Res. 2015;165(2):135–144. doi:10.1007/s12011-015-0234-6
   PubMed Web of Science ®Google Scholar
• Chen R, Zhao LD, Liu H, et al. Fluoride induces neuroinflammation and alters Wnt signaling pathway in BV2 microglial cells. Inflammation. 2017;40(4):1123–1130. doi:10.1007/s10753-017-0556-y
   PubMed Web of Science ®Google Scholar
• Gutowska I, Baranowska-Bosiacka I, Safranow K, et al. Fluoride in low concentration modifies expression and activity of 15 lipoxygenase in human PBMC differentiated monocyte/macrophage. Toxicology. 2012;295(1–3):23–30. doi:10.1016/j.tox.2012.02.014
   PubMed Web of Science ®Google Scholar
• Smith WL, DeWitt DL, Garavito RM. Cyclooxygenases: structural, cellular, and molecular biology. Annu Rev Biochem. 2000;69:145–182. doi:10.1146/annurev.biochem.69.1.145
   PubMed Web of Science ®Google Scholar
• Hara S. Prostaglandin terminal synthases as novel therapeutic targets. Proc Jpn Acad Ser B Phys Biol Sci. 2017;93(9):703–723. doi:10.2183/pjab.93.044
   PubMed Web of Science ®Google Scholar
• Sugimoto Y, Narumiya S. Prostaglandin E receptors. J Biol Chem. 2007;282(16):11613–11617. doi:10.1074/jbc.R600038200
   PubMed Web of Science ®Google Scholar
• Markovic T, Jakopin Z, Dolenc MS, Mlinaric-Rascan I. Structural features of subtype-selective EP receptor modulators. Drug Discov Today. 2017;22(1):57–71. doi:10.1016/j.drudis.2016.08.003
   PubMed Web of Science ®Google Scholar
• M.Metters MK. Prostanoid receptors. In: Annual Reports in Medicinal Chemistry. Vol. 33. Elsevier; 1998.
   Google Scholar
• Vane JR. The fight against rheumatism: from willow bark to COX-1 sparing drugs. J Physiol Pharmacol. 2000;51(4 Pt 1):573–586.
   PubMed Web of Science ®Google Scholar
• Vane JR. Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nat New Biol. 1971;231(25):232–235. doi:10.1038/newbio231232a0
   PubMedGoogle Scholar
• Horl WH. Nonsteroidal anti-inflammatory drugs and the kidney. Pharmaceuticals (Basel). 2010;3(7):2291–2321. doi:10.3390/ph3072291
   PubMedGoogle Scholar
• Xie WL, Chipman JG, Robertson DL, Erikson RL, Simmons DL. Expression of a mitogen-responsive gene encoding prostaglandin synthase is regulated by mRNA splicing. Proc Natl Acad Sci U S A. 1991;88(7):2692–2696. doi:10.1073/pnas.88.7.2692
   PubMed Web of Science ®Google Scholar
• Lee SH, Soyoola E, Chanmugam P, et al. Selective expression of mitogen-inducible cyclooxygenase in macrophages stimulated with lipopolysaccharide. J Biol Chem. 1992;267(36):25934–25938. doi:10.1016/S0021-9258(18)35698-9
   PubMed Web of Science ®Google Scholar
• Liu C, Duan Z, Guan Y, et al. Increased expression of tight junction protein occludin is associated with the protective effect of mosapride against aspirin-induced gastric injury. Exp Ther Med. 2018;15(2):1626–1632. doi:10.3892/etm.2017.5550
   PubMed Web of Science ®Google Scholar
• Yehiyan A, Barman S, Varia H, Pettit S. Short-course high-dose ibuprofen causing both early and delayed jejunal perforations in a non-smoking man. BMJ Case Rep. 2017:bcr-2017-223644. doi:10.1136/bcr-2017-223644
   PubMedGoogle Scholar
• Kim JH, Jin S, Kwon HJ, Kim BW. Curcumin blocks naproxen-induced gastric antral ulcerations through inhibition of lipid peroxidation and activation of enzymatic scavengers in rats. J Microbiol Biotechnol. 2016;26(8):1392–1397. doi:10.4014/jmb.1602.02028
   PubMed Web of Science ®Google Scholar
• Risty GM, Najarian MM, Shapiro SB. Multiple indomethacin-induced jejunal ulcerations with perforation: a case report with histology. Am Surg. 2007;73(4):344–346. doi:10.1177/000313480707300406
   PubMed Web of Science ®Google Scholar
• Kessler WF, Shires GT, Fahey TJ. Surgical complications of nonsteroidal antiinflammatory drug-induced small bowel ulceration. J Am Coll Surg. 1997;185(3):250–254. doi:10.1016/s1072-7515(97)00067-7
   PubMed Web of Science ®Google Scholar
• Washio E, Esaki M, Maehata Y, et al. Proton pump inhibitors increase incidence of nonsteroidal anti-inflammatory drug-induced small bowel injury: a randomized, placebo-controlled trial. Clin Gastroenterol Hepatol. 2016;14(6):809–815. doi:10.1016/j.cgh.2015.10.022
   PubMed Web of Science ®Google Scholar
• Zaffanello M, Brugnara M, Angeli S, Cuzzolin L. Acute non-oliguric kidney failure and cholestatic hepatitis induced by ibuprofen and acetaminophen: a case report. Acta Paediatr. 2009;98(5):903–905. doi:10.1111/j.1651-2227.2008.01209.x
   PubMed Web of Science ®Google Scholar
• Yue Z, Jiang P, Sun H, Wu J. Association between an excess risk of acute kidney injury and concomitant use of ibuprofen and acetaminophen in children, retrospective analysis of a spontaneous reporting system. Eur J Clin Pharmacol. 2014;70(4):479–482. doi:10.1007/s00228-014-1643-8
   PubMed Web of Science ®Google Scholar
• Zhang J, Ding EL, Song Y. Adverse effects of cyclooxygenase 2 inhibitors on renal and arrhythmia events: meta-analysis of randomized trials. JAMA. 2006;296(13):1619–1632. doi:10.1001/jama.296.13.jrv60015
   PubMed Web of Science ®Google Scholar
• Schmidt M, Sorensen HT, Pedersen L. Diclofenac use and cardiovascular risks: series of nationwide cohort studies. BMJ. 2018;362:k3426. doi:10.1136/bmj.k3426
   PubMed Web of Science ®Google Scholar
• Zarghi A, Arfaei S. Selective COX-2 inhibitors: a review of their structure-activity relationships. Iran J Pharm Res. 2011;10(4):655–683.
   PubMed Web of Science ®Google Scholar
• Hegazy R, Alashhab M, Amin M. Cardiorenal effects of newer NSAIDs (Celecoxib) versus classic NSAIDs (Ibuprofen) in patients with arthritis. J Toxicol. 2011;2011:862153. doi:10.1155/2011/862153
   PubMedGoogle Scholar
• Mendes RT, Stanczyk CP, Sordi R, Otuki MF, Dos Santos FA, Fernandes D. Selective inhibition of cyclooxygenase-2: risks and benefits. Rev Bras Reumatol. 2012;52(5):767–782.
   PubMedGoogle Scholar
• Patrono C. Cardiovascular effects of cyclooxygenase-2 inhibitors: a mechanistic and clinical perspective. Br J Clin Pharmacol. 2016;82(4):957–964. doi:10.1111/bcp.13048
   PubMed Web of Science ®Google Scholar
• Bello AE, Holt RJ. Cardiovascular risk with non-steroidal anti-inflammatory drugs: clinical implications. Drug Saf. 2014;37(11):897–902. doi:10.1007/s40264-014-0207-2
   PubMed Web of Science ®Google Scholar
• Neeraja S, Sreenath AS, Reddy PR, Reddanna P. Expression of cyclooxygenase-2 in rat testis. Reprod Biomed Online. 2003;6(3):302–309. doi:10.1016/S1472-6483(10)61849-4
   PubMedGoogle Scholar
• Kirkby NS, Chan MV, Zaiss AK, et al. Systematic study of constitutive cyclooxygenase-2 expression: role of NF-kappaB and NFAT transcriptional pathways. Proc Natl Acad Sci U S A. 2016;113(2):434–439. doi:10.1073/pnas.1517642113
   PubMed Web of Science ®Google Scholar
• Martel-Pelletier J, Lajeunesse D, Reboul P, Pelletier JP. Therapeutic role of dual inhibitors of 5-LOX and COX, selective and non-selective non-steroidal anti-inflammatory drugs. Ann Rheum Dis. 2003;62(6):501–509. doi:10.1136/ard.62.6.501
   PubMed Web of Science ®Google Scholar
• Brune K. Safety of anti-inflammatory treatment—new ways of thinking. Rheumatology. 2004;43(suppl_1):i16–i20. doi:10.1093/rheumatology/keh104
   PubMedGoogle Scholar
• Ye YN, Wu WK, Shin VY, Bruce IC, Wong BC, Cho CH. Dual inhibition of 5-LOX and COX-2 suppresses colon cancer formation promoted by cigarette smoke. Carcinogenesis. 2005;26(4):827–834. doi:10.1093/carcin/bgi012
   PubMed Web of Science ®Google Scholar
• Agarwal S, Reddy GV, Reddanna P. Eicosanoids in inflammation and cancer: the role of COX-2. Expert Rev Clin Immunol. 2009;5(2):145–165. doi:10.1586/1744666X.5.2.145
   PubMed Web of Science ®Google Scholar
• Sala A, Zarini S, Bolla M. Leukotrienes: lipid bioeffectors of inflammatory reactions. Biochemistry (Mosc). 1998;63(1):84–92.
   PubMed Web of Science ®Google Scholar
• Manju SL, Ethiraj KR, Elias G. Safer anti-inflammatory therapy through dual COX-2/5-LOX inhibitors: a structure-based approach. Eur J Pharm Sci. 2018;121:356–381. doi:10.1016/j.ejps.2018.06.003
   PubMed Web of Science ®Google Scholar
• Kulkarni SK, Singh VP. Licofelone–a novel analgesic and anti-inflammatory agent. Curr Top Med Chem. 2007;7(3):251–263. doi:10.2174/156802607779941305
   PubMed Web of Science ®Google Scholar
• Cicero AF, Laghi L. Activity and potential role of licofelone in the management of osteoarthritis. Clin Interv Aging. 2007;2(1):73–79. doi:10.2147/ciia.2007.2.1.73
   PubMed Web of Science ®Google Scholar
• Gaur K, Kori ML, Tyagi LK, et al. Licofelone- Novel Analgesic and Anti-Inflammatory Agent for Osteoarthritis: An Overview. Journal of Young Pharmacists. 2009;1(1):67–71. doi:10.4103/0975-1483.51884.
   Google Scholar
• Koeberle A, Siemoneit U, Buhring U, et al. Licofelone suppresses prostaglandin E2 formation by interference with the inducible microsomal prostaglandin E2 synthase-1. J Pharmacol Exp Ther. 2008;326(3):975–982. doi:10.1124/jpet.108.139444
   PubMed Web of Science ®Google Scholar
• Reddy DB, Reddanna P. Chebulagic acid (CA) attenuates LPS-induced inflammation by suppressing NF-kappaB and MAPK activation in RAW 264.7 macrophages. Biochem Biophys Res Commun. 2009;381(1):112–117. doi:10.1016/j.bbrc.2009.02.022
   PubMed Web of Science ®Google Scholar
• Reddy DB, Reddy TC, Jyotsna G, et al. Chebulagic acid, a COX-LOX dual inhibitor isolated from the fruits of Terminalia chebula Retz., induces apoptosis in COLO-205 cell line. J Ethnopharmacol. 2009;124(3):506–512. doi:10.1016/j.jep.2009.05.022
   PubMed Web of Science ®Google Scholar
• Azad R, Babu NK, Gupta AD, Reddanna P. Evaluation of anti-inflammatory and immunomodulatory effects of Premna integrifolia extracts and assay-guided isolation of a COX-2/5-LOX dual inhibitor. Fitoterapia. 2018;131:189–199. doi:10.1016/j.fitote.2018.10.016
   PubMed Web of Science ®Google Scholar
• Mahipal V. Suraneni GVR, and Reddanna Pallu. NSAIDs, COXIBs, CLOXIBs and Cancer Pain. Horizons Cancer Res. 2011;47.
   Google Scholar
• Hunter LJ, Wood DM, Dargan PI. The patterns of toxicity and management of acute nonsteroidal anti-inflammatory drug (NSAID) overdose. Open Access Emerg Med. 2011;3:39–48. doi:10.2147/OAEM.S22795
   PubMedGoogle Scholar
• Yakovleva OO, Zhamba AO, Doroshkevych IO, Vitruk TK. Cardiac toxicity of coxibs: mechanisms of development and their prevention. Pain Med. 2018;3(3):27–32. doi:10.31636/pmjua.v3i3.3
   Google Scholar
• Morita Y, Aida N, Miyamoto T. Role of phospholipase A2 activation in histamine release from human basophils. Allergy. 1983;38(6):413–418. doi:10.1111/j.1398-9995.1983.tb05084.x
   PubMed Web of Science ®Google Scholar
• Wang D, Dubois RN. Eicosanoids and cancer. Nat Rev Cancer. 2010;10(3):181–193. doi:10.1038/nrc2809
   PubMed Web of Science ®Google Scholar
• Shimizu T. Lipid mediators in health and disease: enzymes and receptors as therapeutic targets for the regulation of immunity and inflammation. Annu Rev Pharmacol Toxicol. 2009;49:123–150. doi:10.1146/annurev.pharmtox.011008.145616
   PubMed Web of Science ®Google Scholar
• Legler DF, Bruckner M, Uetz-von Allmen E, Krause P. Prostaglandin E2 at new glance: novel insights in functional diversity offer therapeutic chances. Int J Biochem Cell Biol. 2010;42(2):198–201. doi:10.1016/j.biocel.2009.09.015
   PubMed Web of Science ®Google Scholar
• Korotkova M, Helmers SB, Loell I, et al. Effects of immunosuppressive treatment on microsomal prostaglandin E synthase 1 and cyclooxygenases expression in muscle tissue of patients with polymyositis or dermatomyositis. Ann Rheum Dis. 2008;67(11):1596–1602. doi:10.1136/ard.2007.079525
   PubMed Web of Science ®Google Scholar
• Gudis K, Tatsuguchi A, Wada K, et al. Microsomal prostaglandin E synthase (mPGES)-1, mPGES-2 and cytosolic PGES expression in human gastritis and gastric ulcer tissue. Lab Invest. 2005;85(2):225–236. doi:10.1038/labinvest.3700200
   PubMed Web of Science ®Google Scholar
• Koeberle A, Werz O. Perspective of microsomal prostaglandin E2 synthase-1 as drug target in inflammation-related disorders. Biochem Pharmacol. 2015;98(1):1–15. doi:10.1016/j.bcp.2015.06.022
   PubMed Web of Science ®Google Scholar
• Samuelsson B, Morgenstern R, Jakobsson PJ. Membrane prostaglandin E synthase-1: a novel therapeutic target. Pharmacol Rev. 2007;59(3):207–224. doi:10.1124/pr.59.3.1
   PubMed Web of Science ®Google Scholar
• Ikeda-Matsuo Y. The role of mPGES-1 in inflammatory brain diseases. Biol Pharm Bull. 2017;40(5):557–563. doi:10.1248/bpb.b16-01026
   PubMed Web of Science ®Google Scholar
• Chang HH, Meuillet EJ. Identification and development of mPGES-1 inhibitors: where we are at? Future Med Chem. 2011;3(15):1909–1934. doi:10.4155/fmc.11.136
   PubMed Web of Science ®Google Scholar
• Bergqvist F, Ossipova E, Idborg H, et al. Inhibition of mPGES-1 or COX-2 results in different proteomic and lipidomic profiles in A549 lung cancer cells. Front Pharmacol. 2019;10:636. doi:10.3389/fphar.2019.00636
   PubMed Web of Science ®Google Scholar
• Riendeau D, Aspiotis R, Ethier D, et al. Inhibitors of the inducible microsomal prostaglandin E-2 synthase (mPGES-1) derived from MK-886. Bioorg Med Chem Lett. 2005;15:3352–3355. doi:10.1016/j.bmcl.2005.05.027
   PubMed Web of Science ®Google Scholar
• Ozen G, Gomez I, Daci A, et al. Inhibition of microsomal PGE synthase-1 reduces human vascular tone by increasing PGI2: a safer alternative to COX-2 inhibition. Br J Pharmacol. 2017;174(22):4087–4098. doi:10.1111/bph.13939
   PubMed Web of Science ®Google Scholar
• Jin Y, Regev A, Kam J, et al. Dose-dependent acute liver injury with hypersensitivity features in humans due to a novel microsomal prostaglandin E synthase 1 inhibitor. Br J Clin Pharmacol. 2018;84(1):179–188. doi:10.1111/bcp.13423
   PubMed Web of Science ®Google Scholar
• Glenmark initiates phase IIb dose range finding study for novel molecule GRC 27864 [press release]. PRNewswire; 2018.
   Google Scholar
• Bergqvist F, Morgenstern R, Jakobsson PJ. A review on mPGES-1 inhibitors: from preclinical studies to clinical applications. Prostaglandins Other Lipid Mediat. 2020;147:106383. doi:10.1016/j.prostaglandins.2019.106383
   PubMed Web of Science ®Google Scholar
• Zhou Z, Yuan Y, Zhou S, Ding K, Zheng F, Zhan CG. Selective inhibitors of human mPGES-1 from structure-based computational screening. Bioorg Med Chem Lett. 2017;27(16):3739–3743. doi:10.1016/j.bmcl.2017.06.075
   PubMed Web of Science ®Google Scholar
• Ding K, Zhou Z, Hou S, et al. Structure-based discovery of mPGES-1 inhibitors suitable for preclinical testing in wild-type mice as a new generation of anti-inflammatory drugs. Sci Rep. 2018;8(1):5205. doi:10.1038/s41598-018-23482-4
   PubMedGoogle Scholar
• Zhou S, Zhou Z, Ding K, et al. DREAM-in-CDM approach and identification of a new generation of anti-inflammatory drugs targeting mPGES-1. Sci Rep. 2020;10(1):10187. doi:10.1038/s41598-020-67283-0
   PubMed Web of Science ®Google Scholar
• Nakanishi M, Gokhale V, Meuillet EJ, Rosenberg DW. mPGES-1 as a target for cancer suppression: A comprehensive invited review “Phospholipase A2 and lipid mediators”. Biochimie. 2010;92(6):660–664. doi:10.1016/j.biochi.2010.02.006
   PubMed Web of Science ®Google Scholar
• Kock A, Larsson K, Bergqvist F, et al. Inhibition of microsomal prostaglandin E synthase-1 in cancer-associated fibroblasts suppresses Neuroblastoma tumor growth. EBioMedicine. 2018;32:84–92. doi:10.1016/j.ebiom.2018.05.008
   PubMed Web of Science ®Google Scholar
• Nakanishi M, Rosenberg DW. Multifaceted roles of PGE2 in inflammation and cancer. Semin Immunopathol. 2013;35(2):123–137. doi:10.1007/s00281-012-0342-8
   PubMed Web of Science ®Google Scholar
• Charles MarkEnsor -H-H. 15-Hydroxyprostaglandin dehydrogenase. J Lipid Mediat Cell Signal. 1995;12(2–3):313–319. doi:10.1016/0929-7855(95)00040-W
   PubMedGoogle Scholar
• Greenhough A, Smartt HJ, Moore AE, et al. The COX-2/PGE2 pathway: key roles in the hallmarks of cancer and adaptation to the tumour microenvironment. Carcinogenesis. 2009;30(3):377–386. doi:10.1093/carcin/bgp014
   PubMed Web of Science ®Google Scholar
• Myung SJ, Rerko RM, Yan M, et al. 15-Hydroxyprostaglandin dehydrogenase is an in vivo suppressor of colon tumorigenesis. Proc Natl Acad Sci U S A. 2006;103(32):12098–12102. doi:10.1073/pnas.0603235103
   PubMed Web of Science ®Google Scholar
• Park JM, Na HK. Erratum: 15-deoxy-delta(12,14)-prostaglandin J2 upregulates the expression of 15-hydroxyprostaglandin dehydrogenase by inducing AP-1 activation and heme oxygenase-1 expression in human colon cancer cells. J Cancer Prev. 2019;24(4):245. doi:10.15430/JCP.2019.24.4.245
   PubMed Web of Science ®Google Scholar
• Monteleone NJ, Moore AE, Iacona JR, Lutz CS, Dixon DA. miR-21-mediated regulation of 15-hydroxyprostaglandin dehydrogenase in colon cancer. Sci Rep. 2019;9(1):5405. doi:10.1038/s41598-019-41862-2
   PubMedGoogle Scholar
• Park YS, Lee JH, Jung DB, et al. MicroRNA-21 induces loss of 15-hydroxyprostaglandin dehydrogenase in early gastric tubular adenocarcinoma. Sci Rep. 2018;8(1):17717. doi:10.1038/s41598-018-36139-z
   PubMedGoogle Scholar
• Arima K, Ohmuraya M, Miyake K, et al. Inhibition of 15-PGDH causes Kras-driven tumor expansion through prostaglandin E2-ALDH1 signaling in the pancreas. Oncogene. 2019;38(8):1211–1224. doi:10.1038/s41388-018-0510-y
   PubMed Web of Science ®Google Scholar
• Yin J, Xia W, Zhang Y, et al. Role of dihydroartemisinin in regulating prostaglandin E2 synthesis cascade and inflammation in endothelial cells. Heart Vessels. 2018;33(11):1411–1422. doi:10.1007/s00380-018-1190-9
   PubMed Web of Science ®Google Scholar
• Wang W, Hu Y, Wang X, Wang Q, Deng H. ROS-mediated 15-hydroxyprostaglandin dehydrogenase degradation via cysteine oxidation promotes NAD(+)-mediated epithelial-mesenchymal transition. Cell Chem Biol. 2018;25(3):255–261 e254. doi:10.1016/j.chembiol.2017.12.008
   PubMed Web of Science ®Google Scholar
• Yao L, Chen W, Song K, et al. 15-hydroxyprostaglandin dehydrogenase (15-PGDH) prevents lipopolysaccharide (LPS)-induced acute liver injury. PLoS One. 2017;12(4):e0176106. doi:10.1371/journal.pone.0176106
   PubMed Web of Science ®Google Scholar
• Karna S. In-vitro wound healing effect of 15-hydroxyprostaglandin dehydrogenase inhibitor from plant. Pharmacogn Mag. 2017;13(Suppl 1):S122–S126. doi:10.4103/0973-1296.203971
   PubMedGoogle Scholar
• Antczak MI, Zhang Y, Wang C, et al. Inhibitors of 15-prostaglandin dehydrogenase to potentiate tissue repair. J Med Chem. 2017;60(9):3979–4001. doi:10.1021/acs.jmedchem.7b00271
   PubMed Web of Science ®Google Scholar
• Smith JNP, Witkin MD, Jogasuria AP, et al. Therapeutic targeting of 15-PGDH in murine pulmonary fibrosis. Sci Rep. 2020;10(1):11657.
   PubMed Web of Science ®Google Scholar
• Sun KH, Karna S, Moon YS, Cho H, Choi CH. The wound-healing effect of 7,3ʹ,4ʹ-trimethoxyflavone through increased levels of prostaglandin E2 by 15-hydroxyprostaglandin dehydrogenase inhibition. Biotechnol Lett. 2017;39(10):1575–1582. doi:10.1007/s10529-017-2386-2
   PubMed Web of Science ®Google Scholar
• Miao S, Lv C, Liu Y, et al. Pharmacologic blockade of 15-PGDH protects against acute renal injury induced by LPS in mice. Front Physiol. 2020;11:138. doi:10.3389/fphys.2020.00138
   PubMed Web of Science ®Google Scholar
• Kim HJ, Lee S, Lee HY, Won H, Chang SH, Nah SS. 15-hydroxyprostaglandin dehydrogenase is upregulated by hydroxychloroquine in rheumatoid arthritis fibroblast-like synoviocytes. Mol Med Rep. 2015;12(3):4141–4148. doi:10.3892/mmr.2015.3931
   PubMed Web of Science ®Google Scholar
• O’Callaghan G, Houston A. Prostaglandin E2 and the EP receptors in malignancy: possible therapeutic targets? Br J Pharmacol. 2015;172(22):5239–5250. doi:10.1111/bph.13331
   PubMed Web of Science ®Google Scholar
• Chen L. Current trends in PGE2 targeting for anti-inflammatory therapy. Pharm Bioprocess. 2016;4(3).
   Google Scholar