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Mini-Reviews in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1389-5575
ISSN (Online): 1875-5607

Mini-Review Article

Rhein Derivatives, A Promising Pivot?

Author(s): Rui Pei, Yueping Jiang, Guanghua Lei , Jingjing Chen , Manhua Liu and Shao Liu *

Volume 21, Issue 5, 2021

Published on: 09 November, 2020

Page: [554 - 575] Pages: 22

DOI: 10.2174/1389557520666201109120855

Price: $65

Abstract

Rhein, an anthraquinone derivative, has been employed widely, especially for the treatment of intractable diseases like diabetic nephropathy, arthritis, and cancer in a unique action mechanism. In the last decades, considerable efforts have been made in structural modification of rhein. This paper reviewed patents on pharmacological activity and therapeutic application of rhein and its derivatives from 1978 to 2018. Particularly, an analysis of patents was made, with the top 10 most valuable patents presented, and the interpretation of the legal status of patents was given. Given the properties of superior pharmacological activity, rich resources, cheap price, low toxicity, and mature extraction process, it is believed that an in-depth investigation on rhein and its derivatives is worth trying.

Keywords: patent, pharmacological activity, rhein, therapeutic application, anthraquinone derivative, drug development.

Graphical Abstract
[1]
Zhou, Y-X.; Xia, W.; Yue, W.; Peng, C.; Rahman, K.; Zhang, H. Rhein: A review of pharmacological activities. Evid. Based Complement. Alternat. Med., 2015.578107
[http://dx.doi.org/10.1155/2015/578107] [PMID: 26185519]
[2]
Sun, H.; Luo, G.; Chen, D.; Xiang, Z. A Comprehensive and system review for the pharmacological mechanism of action of rhein, an active anthraquinone ingredient. Front. Pharmacol., 2016, 7, 247.
[http://dx.doi.org/10.3389/fphar.2016.00247] [PMID: 27582705]
[3]
Zeng, C-C.; Liu, X.; Chen, G-R.; Wu, Q-J.; Liu, W-W.; Luo, H-Y.; Cheng, J.G. The molecular mechanism of rhein in diabetic nephropathy. Evid. Based Complement. Alternat. Med., 2014.2014487097
[http://dx.doi.org/10.1155/2014/487097] [PMID: 25435889]
[4]
Wan, P.; Sun, J.G.; Hao, G.; Zhang, X.X.; Xiao, D.W.; Liu, Z.H. Determination of rhein in plasma, urine and feces by HPLC-fluorescence detection and its pharmacokinetics in healthy volunteers. J. China Pharm. Univ., 2013, 44, 73-76.
[5]
Spencer, C.M.; Wilde, M.I. Diacerein. Drugs, 1997, 53(1), 98-106.
[http://dx.doi.org/10.2165/00003495-199753010-00007] [PMID: 9010651]
[6]
Hussain, H. AI-Harrasi, A.; AI-Rawahi, A.; Green, I.R.; Csuk, R.; Ahmed, I.; Shah, A.; Abbas, G.; Rehman, N.U.; Ullah, R. A fruitful decade from 2005 to 2014 for anthraquinone patents. Expert Opin. Ther. Pat., 2015, 25, 1053-1064.
[http://dx.doi.org/10.1517/13543776.2015.1050793]
[7]
Lee, J-H.; Kim, J.M.; Kim, C. Pharmacokinetic analysis of rhein in Rheum undulatum L. J. Ethnopharmacol., 2003, 84(1), 5-9.
[http://dx.doi.org/10.1016/S0378-8741(02)00222-2] [PMID: 12499069]
[8]
Antonisamy, P.; Agastian, P.; Kang, C-W.; Kim, N.S.; Kim, J-H. Anti-inflammatory activity of rhein isolated from the flowers of Cassia fistula L. and possible underlying mechanisms. Saudi J. Biol. Sci., 2019, 26(1), 96-104.
[http://dx.doi.org/10.1016/j.sjbs.2017.04.011] [PMID: 30622412]
[9]
Hu, G.; Liu, J.; Zhen, Y-Z.; Wei, J.; Qiao, Y.; Lin, Y-J.; Tu, P. Rhein inhibits the expression of vascular cell adhesion molecule 1 in human umbilical vein endothelial cells with or without lipopolysaccharide stimulation. Am. J. Chin. Med., 2013, 41(3), 473-485.
[http://dx.doi.org/10.1142/S0192415X13500341] [PMID: 23711136]
[10]
Cong, X-D.; Ding, M-J.; Dai, D-Z.; Wu, Y.; Zhang, Y.; Dai, Y. ER stress, p66shc, and p-Akt/Akt mediate adjuvant-induced inflammation, which is blunted by argirein, a supermolecule and rhein in rats. Inflammation, 2012, 35(3), 1031-1040.
[http://dx.doi.org/10.1007/s10753-011-9407-4] [PMID: 22095404]
[11]
Martin, G.; Bogdanowicz, P.; Domagala, F.; Ficheux, H.; Pujol, J-P. Rhein inhibits interleukin-1 beta-induced activation of MEK/ERK pathway and DNA binding of NF-kappa B and AP-1 in chondrocytes cultured in hypoxia: A potential mechanism for its disease-modifying effect in osteoarthritis. Inflammation, 2003, 27(4), 233-246.
[http://dx.doi.org/10.1023/A:1025040631514] [PMID: 14527176]
[12]
Proter, S.P.A. Anthraquinone derivatives for the treatment of arthritis, IT1098332B1985.
[13]
Friedmann, CA Anthraquinone derivatives for the treatment of arthritis, FR2508798B11986.
[14]
Dall’asta, L; Coppi, G; Scevola, M.E. Diacetylrhein potassium salt and its therapeutical use in the treatment of arthritis, EP0243968B11991.
[15]
Cong, X.D.; Zhang, Y.; Dai, D.Z.; Dai, Y.; Chen, G.X. Application of complexes of rhein or rhein compounds in preparation of medicine for treating osteoarthritis, CN1899275B2013.
[16]
Cong, X.D.; Zhang, Y.; Dai, D.Z.; Dai, Y.; Chen, G.X. Application of complexes of rhein or rhein compounds in preparation of medicine for treating diabetic nephropathy, CN1899277B2013.
[17]
Cong, X.D.; Zhang, Y.; Dai, D.Z.; Dai, Y.; Chen, G.X. Application of complexes of rhein or rhein compounds in preparation of medicine for recovery of gastrointestinal function and prevention of intestinal adhesion, CN1899276B2014.
[18]
Cong, X.D.; Dai, D.Z.; Zhang, Y.; Dai, Y. Application of complexes of rhein or rhein compounds and arginine in preparing medicine for treating diabetic vascular complications, CN103202829A2013.
[19]
Cong, X.D.; Dai, D.Z.; Zhang, Y.; Dai, Y. Application of complexes of rhein or rhein compound and arginine in preparing medicine for treating diabetic vascular complications, CN103169690A2013.
[20]
Liu, D.H.; Zhao, Z.Y. A Chinese medicle powder injection for treating arthritis and its preparation method, CN1712041A2005.
[21]
Charbit, S.; Schutze, F.; Provvedini, D.; Ficheux, H. Use of a rhein in a therapeutic treatment requiring a rise in the rate of heme oxygenase, US20060058392A12006.
[22]
Brown, C.O., III; Chen, Z.G.; Li, J.Y.; Lu, W.S. Diacerein or its analogs for inhibiting the expression of ASC, the expression of NLRP3 and/or the formation of NLRP3 inflammatory complexes, CN108349867A, 2018.
[23]
Pietrangelo, A; Travagli, V Esters of hyaluronic acid with rhein, process for their preparation and compositions comprising the same, EP1718679B12007.
[24]
Carlino, S.; Napoli, A.D. Dioxoanthracene sulphonate derivatives, EP2220036B12012.
[25]
Rosini, S; Mian, M. 4,5-dihydroxy- and 4,5,8-trihydroxy- 9,10-dihydro-9,10-dioxo-2-anthracenecarboxylic acid dicarbonates and urethans having therapeutical activities, US5362750A1994.
[26]
Rosini, S.; Mian, M. Acylamino-alkyliden-hydroxy-bisphosphonic acids esters and salts thereof, wherein the acyl group is derived from an acid having antiinflammatory activity, US5466682A1995.
[27]
Rosini, S.; Mian, M. Anthraquinone compounds useful to treat osteoarticular conditions, pharmaceutical compositions and method of treatment, US5451606A1995.
[28]
Rosini, S; Mian, M. Arylalkyl esters of 4,5-dihydroxy-9,10-dihydro-9,10-dioxo-2-anthracenecarboxylic acid having therapeutical activity, US5330981A, 1994.
[29]
Cifter, U.; Turkyilmaz, A. AKALIN N.P.; ZENGINER, S.; Mutlu, O. Combinations of diacerein and non-steroidal inflammation drugs, EP2797584B12015.
[30]
Benetti, D; Aloisi, R; Guainai, G; Rosini, S. Mono- and disulfosubstituted anthraquinones and their use for the treatment of bone matrix disorders, US5856358A1999.
[31]
Napoli, G.D. Rhein derivatives and new processes for producing rhein derivatives, US5864048A1999.
[32]
Quirk, S. Matrix metalloproteinase inhibitors, US6600057B22003.
[33]
Bannister, R.M.; Baxter, A.D.; Cooper, N.; Brew, J. 1,8-dihydroxyanthraquinone-6-carboxamide derivatives as modulators of IL-10 production for treatment of autoimmune or inflammatory conditions, GB2398779A2004.
[34]
Baxter, A.D.; Walmsley, A. Ester derivatives of rhein and their therapeutic use, US7728035B22010.
[35]
Li, J.C.; Huang, P.; Liu, Y.W. Rhein derivatives and their therapeutic use, CN102225913B2013.
[36]
Li, J.C.; Huang, P.; Niu, Q. Ether derivatives of rhein and their therapeutic use, CN102225896B2013.
[37]
Jiang, M.; Xu, X.; Qi, X.Y.; Yang, C.H.; Deng, L.F. A class of rhein compounds and their uses, CN105884645B2018.
[38]
Xu, X.; Qi, X.; Yan, Y.; Qi, J.; Qian, N.; Guo, L.; Li, C.; Wang, F.; Huang, P.; Zhou, H.; Jiang, M.; Yang, C.; Deng, L. Synthesis and biological evaluation of rhein amides as inhibitors of osteoclast differentiation and bone resorption. Eur. J. Med. Chem., 2016, 123, 769-776.
[http://dx.doi.org/10.1016/j.ejmech.2016.08.004] [PMID: 27541260]
[39]
Jiang, M.; Xu, X.; Deng, L.F.; Jiang, B.; Yang, C.H. Rhein thioamide compounds,their preparation and use, CN107298648B2019.
[40]
Jiang, M.; Wang, T.; Yan, X.; Liu, Z.; Yan, Y.; Yang, K.; Qi, J.; Zhou, H.; Qian, N.; Zhou, Q.; Chen, B.; Xu, X.; Xi, X.; Yang, C.; Deng, L. A novel rhein derivative modulates bone formation and resorption and ameliorates estrogen-dependent bone loss. J. Bone Miner. Res., 2019, 34(2), 361-374.
[http://dx.doi.org/10.1002/jbmr.3604] [PMID: 30320929]
[41]
Behera, J.; Tyagi, S.C.; Tyagi, N. Role of hydrogen sulfide in the musculoskeletal system. Bone, 2019, 124, 33-39.
[http://dx.doi.org/10.1016/j.bone.2019.03.034] [PMID: 30928641]
[42]
Li, L.Z.; Cui, Y.; Zhang, Y.L.; Cui, Y. Rhubarb anthraquinone derivatives, and their preparation and pharmaceutical compositions, CN100368426C2008.
[43]
Tang, L.; Wang, J.T.; Zhu, G.F. Bisphosphonate rhein ether derivatives with bone affinities and their preparation method, CN101735271A2010.
[44]
Ji, M.; Duan, Y.B.; Yu, J. Synthesis method and application of bone-targeted anti-inflammatory drugs, CN101475484B2012.
[45]
Cai, J.; Duan, Y.; Yu, J.; Chen, J.; Chao, M.; Ji, M. Bone-targeting glycol and NSAIDS ester prodrugs of rhein: Synthesis, hydroxyapatite affinity, stability, anti-inflammatory, ulcerogenicity index and pharmacokinetics studies. Eur. J. Med. Chem., 2012, 55, 409-419.
[http://dx.doi.org/10.1016/j.ejmech.2012.07.053] [PMID: 22901311]
[46]
Xie, H.B.; Gu, S.H.; Lv, W.H.; Li, Q.Y.; Hu, H.F. Rhein derivatives and their application, CN104926754A2015.
[47]
Xie, H.B.; Gu, S.H.; Lv, W.H.; Li, Q.Y. A carboxylic ester derivative of rhein and its application, CN104945269A2015.
[48]
Chen, L.J.; Li, Y.; Wang, X.; Jia, D.C.; Cui, Q.G. Rhein ester derivatives and their preparation and application, CN106631808A2017.
[49]
Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R.L.; Torre, L.A.; Jemal, A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2018, 68(6), 394-424.
[http://dx.doi.org/10.3322/caac.21492] [PMID: 30207593]
[50]
Yang, L.; Lin, S.; Kang, Y.; Xiang, Y.; Xu, L.; Li, J.; Dai, X.; Liang, G.; Huang, X.; Zhao, C. Rhein sensitizes human pancreatic cancer cells to EGFR inhibitors by inhibiting STAT3 pathway. J. Exp. Clin. Cancer Res., 2019, 38(1), 31.
[http://dx.doi.org/10.1186/s13046-018-1015-9] [PMID: 30674340]
[51]
Gallagher, P.T.; Owton, W.M.; Williams, A.C. Pharmaceutical compounds, US5792797A1998.
[52]
Yang, C.H.; Miu, Z.H.; Yue, Z.Z.; Liang, Y.K.; Feng, J.M.; Li, J.X; He, Q. Anthraquinone and thiazole compound, preparation method and application thereof, CN104250246B2017.
[53]
Wang, H.S.; Huang, R.Z.; Pan, Y.M.; Yao, G.Y.; Dai, W.L.; Ye, M.Y; Chen, Z.F Rhein aminophosphonate derivatives,and their synthesis method and application, CN103524555B2016.
[54]
Wang, H.S.; Huang, R.Z.; Pan, Y.M.; Yao, G.Y.; Dai, W.L.; Ye, M.Y; Chen, Z.F. Diacerein aminophosphonate derivatives,and their synthesis method and application, CN103524556B2016.
[55]
He, L.Q.; Huang, J.K. Rhein aminol ester derivatives,their preparation and medical use, CN103709052B2016.
[56]
Huang, J.K.; He, L.Q.; Huang, P.; Bai, Z.W.; Zhang, W.W. Synthesis of rhein aminol ester derivatives and their anti-osteosarcoma cell activity. Acta Pharm., 2018, 53, 249-255.
[57]
Lin, Y.J.; Zhen, Y.S.; Liu, X.J.; Wu, S.Y.; Xu, X.D. Preparation process of lysine rhein and its application in tumor therapy, CN101255121B2012.
[58]
Lin, Y.J. Preparation of lysine rhein and its anti-tumor mechanism. Ph.D; Peking Union Medical College, 2008.
[59]
Xu, W.Q.; Li, J.Y.; Zhu, Z.H.; Li, G.Q.; Shen, X.; Zhang, Y.J. Rhein derivatives,their synthesis method and use, CN103864642B2016.
[60]
Xie, J.W.; Zhou, C.J.; Dai, B.; Zhang, J.; Liu, P. A rhein compound and its preparation and application, CN104557603A2015.
[61]
Chen, H.S. Platinum salts of organic acids, preparation thereof and application in preparation of anticancer drugs, CN101289467A2008.
[62]
Ou, B.N.; Li, L.Q. Ester derivatives of rhein polyol and their use for preparing antitumor medicine, CN104529782A2015.
[63]
Liu, H.K.; Kong, Y.Q.; Qian, Y.; Su, Z.; Li, J.; Wu, J. Organic compounds modified by rhein-specific group, and their aryl metal complex, preparation method and application, CN108530343A2018.
[64]
Yang, X.; Sun, G.; Yang, C.; Wang, B. Novel rhein analogues as potential anticancer agents. ChemMedChem, 2011, 6(12), 2294-2301.
[http://dx.doi.org/10.1002/cmdc.201100384] [PMID: 21954017]
[65]
Gu, L.; Zhang, H.; Liu, T.; Draganov, A.; Yi, S.; Wang, B.; Zhou, M. Inhibition of MDM2 by a rhein-derived compound AQ-101 suppresses cancer development in SCID mice. Mol. Cancer Ther., 2018, 17(2), 497-507.
[http://dx.doi.org/10.1158/1535-7163.MCT-17-0566] [PMID: 29282301]
[66]
Wang, B.H.; Dai, C.F.; Draganov, A.; Yang, X.C.; Sun, G.J.; Yang, C.H.; Chen, W.X.; Ni, N.T.; Zhou, M.X.; Gu, L.B. Anthraquinone analogs and methods of making and using thereof US20150203442A1, 2015.
[67]
Hou, H.X.; Tian, W.; Li, D.R. Preparation and application of an anthraquinone compound for inducing para-apoptosis of liver cancer cells, CN108586278A2018.
[68]
Cho, N.H.; Shaw, J.E.; Karuranga, S.; Huang, Y.; da Rocha Fernandes, J.D.; Ohlrogge, A.W.; Malanda, B. IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res. Clin. Pract., 2018, 138, 271-281.
[http://dx.doi.org/10.1016/j.diabres.2018.02.023] [PMID: 29496507]
[69]
Diagnosis and classification of diabetes mellitus. Diabetes Care, 2014, 37, S81-S90.
[http://dx.doi.org/10.2337/dc14-S081] [PMID: 24357215]
[70]
Zheng, J-M.; Zhu, J-M.; Li, L-S.; Liu, Z-H. Rhein reverses the diabetic phenotype of mesangial cells over-expressing the glucose transporter (GLUT1) by inhibiting the hexosamine pathway. Br. J. Pharmacol., 2008, 153(7), 1456-1464.
[http://dx.doi.org/10.1038/bjp.2008.26] [PMID: 18264122]
[71]
Li, L.S. Use of rhein or rhein salts in the preparation of medicine for treating diabetic nephropathy, CN1086289C2002.
[72]
Zhang, Y. Application of rhein or its salt in preparing medicine for treating chronic nephritis or chronic renal failure, CN101301284B2010.
[73]
Wang, C.P.; Sun, W.X.; Fang, Z.; Lu, C.L.; Zhu, Z.H.; Mao, L.Z.; Zhang, H.Y.; Zhu, M.H; Zhang, H.Y.; Zhu, M.H. Rhein and berberine ion pair compound, its preparation method and application, CN103319479B2015.
[74]
Gu, S.H.; Cao, H.; Sun, W.X. A rhein derivative and its preparation and use, CN102060809B2015.
[75]
Li, X.G.; Zhu, X.K.; Ye, X.L. 3-alkoxy-6-carboxyl rhein or pharmaceutically acceptable salt, and their preparation method and application, CN101613271B2013.
[76]
Zhang, F.Y.; Chen, Q.Y. Water-soluble choline salt of rhein and its derivatives, their preparation and application in medicine, CN103965062A2014.
[78]
Nalivaeva, N.N.; Turner, A.J. AChE and the amyloid precursor protein (APP) - Cross-talk in Alzheimer’s disease. Chem. Biol. Interact., 2016, 256(Pt B), 301-306.
[http://dx.doi.org/10.1016/j.cbi.2016.04.009] [PMID: 27062894]
[79]
Viayna, E.; Sola, I.; Bartolini, M.; De Simone, A.; Tapia-Rojas, C.; Serrano, F.G.; Sabaté, R.; Juárez-Jiménez, J.; Pérez, B.; Luque, F.J.; Andrisano, V.; Clos, M.V.; Inestrosa, N.C.; Muñoz-Torrero, D. Synthesis and multitarget biological profiling of a novel family of rhein derivatives as disease-modifying anti-Alzheimer agents. J. Med. Chem., 2014, 57(6), 2549-2567.
[http://dx.doi.org/10.1021/jm401824w] [PMID: 24568372]
[80]
López-Ibarra, D.M.T.; Cantín, N.M.I; Gaza, E.V.; Lao, I.S.; Cruz, S.V. Beta-amyloid-directed multitarget compounds for the treatment of alzheimer’s disease, US9238626B22016.
[81]
Liu, J.B. Esters of anthraquinone acid and kojic acid, and their application as tyrosinase inhibitors, CN108546259A2018.
[82]
Liu, J.B. Application of rhein and its vitamin C ester derivatives as tyrosinase inhibitors, CN108586400A2018.
[83]
Oliveira, S.; Pijoan, C. Haemophilus parasuis: New trends on diagnosis, epidemiology and control. Vet. Microbiol., 2004, 99(1), 1-12.
[http://dx.doi.org/10.1016/j.vetmic.2003.12.001] [PMID: 15019107]
[84]
Hua, X.; Liu, S.G.; Zhang, W.J. A medicine for preventing and treating haemophilus parasuis and its application, CN106955280A2017.
[85]
Yang, J.Q.; Zhao, S.X.; An, J.L.; Deng, L.; Lei, Y.Y. Rhein ester derivatives and their preparation method and application, CN109053798A2018.
[86]
Qin, Y.; Sheng, X.Y. Application of rhein in the prevention and treatment of fatty liver, CN101327204B2010.
[87]
Liu, L.P. Conjugated compounds of ursodeoxycholic acid with berberine or L-carnitine and their composition and method, CN108137575A2018.
[88]
Ju, X.W.; Hou, X.H.; Fan, G.P.; Bai, S.F.; Zhang, J.Z.; An, Q.; Chen, H. Synthesis and bone affinity of rhein-N-β-hydroxyethyl tegafurate. J. Chin. People’s Armed Police Acad., 2008, 375-377.
[89]
Wang, Z.M.; Chen, H.; Cao, B.; Wang, Y.; Mou, H.J. Study on the mechanism of action of rhodophyllotoxin ester on human osteosarcoma cells. Chin. Herb. Med., 2008, 67-71.
[90]
Dhaneshwar, S.S.; Patil, D.; Mengi, S.; Mulay, G.; Lahane, J. Diacerein mutual prodrug for osteoarthritis: Synthesis, in vitro kinetic studies and preliminary pharmacological screening. J. Drug Deliv. Sci. Technol., 2009, 19, 25-29.
[http://dx.doi.org/10.1016/S1773-2247(09)50003-2]
[91]
Suneela, D.; Dipmala, P. Synthesis and pharmacokinetic profile of rhein- boswellic acid conjugate. Bioorg. Med. Chem. Lett., 2012, 22(24), 7582-7587.
[http://dx.doi.org/10.1016/j.bmcl.2012.10.017] [PMID: 23107483]
[92]
Dhaneshwar, S.; Patel, V.; Patil, D.; Meena, G. Studies on synthesis, stability, release and pharmacodynamic profile of a novel diacerein-thymol prodrug. Bioorg. Med. Chem. Lett., 2013, 23(1), 55-61.
[http://dx.doi.org/10.1016/j.bmcl.2012.11.016] [PMID: 23218603]
[93]
Li, S-Y.; Jiang, N.; Xie, S-S.; Wang, K.D.G.; Wang, X-B.; Kong, L-Y. Design, synthesis and evaluation of novel tacrine-rhein hybrids as multifunctional agents for the treatment of Alzheimer’s disease. Org. Biomol. Chem., 2014, 12(5), 801-814.
[http://dx.doi.org/10.1039/C3OB42010H] [PMID: 24310227]
[94]
Yuan, Y-F.; Hu, X-Y.; He, Y.; Deng, J-G. Synthesis and anti-tumor activity evaluation of rhein-aloe emodin hybrid molecule. Nat. Prod. Commun., 2012, 7(2), 207-210.
[http://dx.doi.org/10.1177/1934578X1200700223] [PMID: 22474959]
[95]
Xiang, H. Research on the structure and pharmacological action of rhein metal complex. Master; Chengdu University of Traditional Chinese Medicine, 2014.
[96]
Wang, X.D.; Li, L.; Han, Y.P. Synthesis and antibacterial activity of rhein derivatives. Forest Prod. Chem. Indust., 2018, 38, 105-111.
[97]
Panova, E.; Jones, G. Benefit-risk assessment of diacerein in the treatment of osteoarthritis. Drug Saf., 2015, 38(3), 245-252.
[http://dx.doi.org/10.1007/s40264-015-0266-z] [PMID: 25652235]
[98]
Pavelka, K.; Bruyère, O.; Cooper, C.; Kanis, J.A.; Leeb, B.F.; Maheu, E.; Martel-Pelletier, J.; Monfort, J.; Pelletier, J.P.; Rizzoli, R.; Reginster, J.Y. Diacerein: Benefits, risks and place in the management of osteoarthritis. An opinion-based report from the ESCEO. Drugs Aging, 2016, 33(2), 75-85.
[http://dx.doi.org/10.1007/s40266-016-0347-4] [PMID: 26849131]
[99]
Zhang, Q.; Zhou, J.T.; Wang, Y.S.; Chen, D.C. The effect and safety of diacerein in patients with type 2 diabetes mellitus: A systematic review and meta-analysis. Am. J. Clin. Exp. Immunol., 2017, 6(6), 97-106.
[PMID: 29348985]
[100]
Ablinger, M.; Felder, T.K.; Wimmer, M.; Zauner, R.; Hofbauer, P.; Lettner, T.; Wolkersdorfer, M.; Lagler, F.B.; Diem, A.; Bauer, J.W.; Wally, V. Basal pharmacokinetic parameters of topically applied diacerein in pediatric patients with generalized severe epidermolysis bullosa simplex. Orphanet J. Rare Dis., 2018, 13(1), 193.
[http://dx.doi.org/10.1186/s13023-018-0940-1] [PMID: 30382914]
[101]
Wally, V.; Hovnanian, A.; Ly, J.; Buckova, H.; Brunner, V.; Lettner, T.; Ablinger, M.; Felder, T.K.; Hofbauer, P.; Wolkersdorfer, M.; Lagler, F.B.; Hitzl, W.; Laimer, M.; Kitzmüller, S.; Diem, A.; Bauer, J.W. Diacerein orphan drug development for epidermolysis bullosa simplex: A phase 2/3 randomized, placebo-controlled, double-blind clinical trial. J. Am. Acad. Dermatol., 2018, 78(5), 892-901.e7.
[http://dx.doi.org/10.1016/j.jaad.2018.01.019] [PMID: 29410318]

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