Recent Development of Small Molecule Drugs for the Treatment of Osteoarthritis

Xiaofei Zhang, Chunhao Yang

Prog Chem ›› 2024, Vol. 36 ›› Issue (12) : 1849-1858.

PDF(2912 KB)
Home Journals Progress in Chemistry
Progress in Chemistry

Abbreviation (ISO4): Prog Chem      Editor in chief: Jincai ZHAO

About  /  Aim & scope  /  Editorial board  /  Indexed  /  Contact  / 
PDF(2912 KB)
Prog Chem ›› 2024, Vol. 36 ›› Issue (12) : 1849-1858. DOI: 10.7536/PC241115
Chemistry: A Century of Life-Special Edition

Recent Development of Small Molecule Drugs for the Treatment of Osteoarthritis

Author information +
History +

Abstract

Osteoarthritis is a common degenerative disease in middle-aged and elderly people, and its lesions involve the entire joint, such as cartilage, subchondral bone and synovial membrane. Although there are some launched drugs that can be used to relieve the pain caused by osteoarthritis, the therapeutic effects are insufficient and there are some certain side effects. For now, except for artificial joint replacement for late stage of osteoarthritis, there are no effective drugs for early and middle stage of osteoarthritis to delay its progression. The treatment of osteoarthritis in clinical faces a huge demand for valid drugs, but the development of therapeutic drugs is way behind schedule. This review focuses on the progress of small molecule drugs for the treatment of osteoarthritis, especially the small molecule chemical entities which have entered the clinical trial stage. We hope this article will provide inspiration for the researchers on the drug development of osteoarthritis.

Contents

1 Introduction of osteoarthritis

2 Features of osteoarthritis

3 Small molecule drugs against osteoarthritis

3.1 Clinical small molecule drugs against osteoarthritis

3.2 The development of small molecule disease- modifying osteoarthritis drugs (DMOADs)

4 Conclusion and outlook

Key words

osteoarthritis / small molecule drugs / drug development

Cite this article

Download Citations
Xiaofei Zhang , Chunhao Yang. Recent Development of Small Molecule Drugs for the Treatment of Osteoarthritis[J]. Progress in Chemistry. 2024, 36(12): 1849-1858 https://doi.org/10.7536/PC241115

References

[1]
Glyn-Jones S, Palmer A J R, Agricola R, Price A J, Vincent T L, Weinans H, Carr A J. Lancet, 2015, 386(9991): 376.
[2]
Shane Anderson A, Loeser R F. Best Pract. Res. Clin. Rheumatol., 2010, 24(1): 15.
[3]
Kulkarni K, Karssiens T, Kumar V, Pandit H. Maturitas, 2016, 89: 22.
[4]
Valdes A M, Spector T D. Rheum. Dis. Clin. N Am, 2008, 34(3): 581.
[5]
Gignac M A M, Irvin E, Cullen K, Van Eerd D, Beaton D E, Mahood Q, McLeod C, Backman C L. Arthritis Care Res., 2020, 72(3): 378.
[6]
Anderson D D, Chubinskaya S, Guilak F, Martin J A, Oegema T R, Olson S A, Buckwalter J A. J. Orthop. Res., 2011, 29(6): 802.
[7]
Li Y S, Xie W Q, Xiao W F, Dou D. Bone Res., 2022, 10: 41.
[8]
Thysen S, Luyten F P, Lories R J U. Dis. Models Mech., 2015, 8(1): 17.
[9]
Kraus V B, Simon L S, Katz J N, Neogi T, Hunter D, Guermazi A, Karsdal M A. Osteoarthr. Cartil., 2019, 27(4): 571.
[10]
Wieland H A, Michaelis M, Kirschbaum B J, Rudolphi K A. Nat. Rev. Drug Discov., 2005, 4(4): 331.
[11]
Deschaseaux F, Sensébé L, Heymann D. Trends Mol. Med., 2009, 15(9): 417.
[12]
Martel-Pelletier J, Boileau C, Pelletier J P, Roughley P J. Best Pract. Res. Clin. Rheumatol., 2008, 22(2): 351.
[13]
Hu Y, Chen X, Wang S C, Jing Y Y, Su J C. Bone Res., 2021, 9: 20.
[14]
Berenbaum F. Osteoarthr. Cartil., 2013, 21(1): 16.
[15]
Goldring M B, Otero M. Curr. Opin. Rheumatol., 2011, 23(5): 471.
[16]
Wada T, Nakashima T, Hiroshi N, Penninger J M. Trends Mol. Med., 2006, 12(1): 17.
[17]
Rigoglou S, Papavassiliou A G. Int. J. Biochem. Cell Biol., 2013, 45(11): 2580.
[18]
Velasco J, Zarrabeitia M T, Prieto J R, Perez-Castrillon J L, Perez-Aguilar M D, Perez-Nuñez M I, Sañudo C, Hernandez-Elena J, Calvo I, Ortiz F, Gonzalez-Macias J, Riancho J A. Osteoporos. Int., 2010, 21(1): 109.
[19]
Zhai G J, Doré J, Rahman P. Rheumatol. Int., 2015, 35(8): 1283.
[20]
Daheshia M, Yao J Q. J. Rheumatol., 2008, 35(12): 2306.
[21]
Walsh D A, Stocks J. SLAS Discov., 2017, 22(8): 931.
[22]
Roth S H, Anderson S. Phys. Sportsmed., 2011, 39(3): 62.
[23]
Jeffery M M, Hooten W M, Henk H J, Bellolio M F, Hess E P, Meara E, Ross J S, Shah N D. BMJ, 2018, 362: k2833.
[24]
Samuels J, Pillinger M H, Jevsevar D, Felson D, Simon L S. Osteoarthritis Cartilage, 2021, 29(1): 8.
[25]
Bottegoni C, Muzzarelli R A A, Giovannini F, Busilacchi A, Gigante A. Carbohydr. Polym., 2014, 109: 126.
[26]
Kucharz E J, Kovalenko V, Szántó S, Bruyère O, Cooper C, Reginster J. Y. Curr. Med. Res. Opin., 2016, 32(6): 997.
[27]
Oo W M, Little C, Duong V, Hunter D J. Drug Des. Dev. Ther., 2021, 15: 2921.
[28]
Krishnan Y, Grodzinsky A J. Matrix Biol., 2018, 71: 51.
[29]
Aranapakam V, Grosu G T, Davis J M, Hu B H, Ellingboe J, Baker J L, Skotnicki J S, Zask A, DiJoseph J F, Sung A, Sharr M A, Killar L M, Walter T, Jin G X, Cowling R. J. Med. Chem., 2003, 46(12): 2361.
[30]
Yamada A, Uegaki A, Nakamura T, Ogawa K. Inflamm. Res., 2000, 49(4): 144.
[31]
Leff R L, Elias I, Ionescu M, Reiner A, Poole A R. J. Rheumatol., 2003, 30(3): 544.
[32]
Vandenbroucke R E, Libert C. Nat. Rev. Drug Discov., 2014, 13(12): 904.
[33]
Schnute M E, O’Brien P M, Nahra J, Morris M, Howard Roark W, Hanau C E, Ruminski P G, Scholten J A, Fletcher T R, Hamper B C, Carroll J N, Patt W C, Shieh H S, Collins B, Pavlovsky A G, Palmquist K E, Aston K W, Hitchcock J, Rogers M D, McDonald J, Johnson A R, Munie G E, Wittwer A J, Man C F, Settle S L, Nemirovskiy O, Vickery L E, Agawal A, Dyer R D, Sunyer T. Bioorg. Med. Chem. Lett., 2010, 20(2): 576.
[34]
Wang M N, Sampson E R, Jin H T, Li J, Ke Q H, Im H J, Chen D. Arthritis Res. Ther., 2013, 15(1): R5.
[35]
Piecha D, Weik J, Kheil H, Becher G, Timmermann A, Jaworski A, Burger M, Hofmann M W. Inflamm. Res., 2010, 59(5): 379.
[36]
De Savi C, Waterson D, Pape A, Lamont S, Hadley E, Mills M, Page K M, Bowyer J, Maciewicz R A. Bioorg. Med. Chem. Lett., 2013, 23(16): 4705.
[37]
Glasson S S, Askew R, Sheppard B, Carito B, Blanchet T, Ma H L, Flannery C R, Peluso D, Kanki K, Yang Z, Majumdar M K, Morris E A. Nature, 2007, 446(7131): 102.
[38]
van der Aar E M, Desrivot J, Fagard L, Amantini D, Larsson S, Struglics A, Lohmander S, Vanhoutte F, Dupont S. Osteoarthr. Cartil., 2018, 26: S310.
[39]
Chockalingam P S, Sun W, Rivera-Bermudez M A, Zeng W, Dufield D R, Larsson S, Lohmander L S, Flannery C R, Glasson S S, Georgiadis K E, Morris E A. Osteoarthr. Cartil., 2011, 19(3): 315.
[40]
Nusse R, Clevers H. Cell, 2017, 169(6): 985.
[41]
Lambert C, Dubuc J E, Montell E, Vergés J, Munaut C, Noël A, Henrotin Y. Arthritis Rheumatol., 2014, 66(4): 960.
[42]
Kahn M. Nat. Rev. Drug Discov., 2014, 13(7): 513.
[43]
Deshmukh V, O’Green A L, Bossard C, Seo T, Lamangan L, Ibanez M, Ghias A, Lai C, Do L, Cho S, Cahiwat J, Chiu K, Pedraza M, Anderson S, Harris R, Dellamary L, Kc S, Barroga C, Melchior B, Tam B, Kennedy S, Tambiah J, Hood J, Yazici Y. Osteoarthr. Cartil., 2019, 27(9): 1347.
[44]
Yazici Y, McAlindon T E, Fleischmann R, Gibofsky A, Lane N E, Kivitz A J, Skrepnik N, Armas E, Swearingen C J, DiFrancesco A, Tambiah J R S, Hood J, Hochberg M C. Osteoarthr. Cartil., 2017, 25(10): 1598.
[45]
Yazici Y, McAlindon T E, Gibofsky A, Lane N E, Clauw D, Jones M, Bergfeld J, Swearingen C J, DiFrancesco A, Simsek I, Tambiah J, Hochberg M C. Arthritis Rheumatol., 2020, 72(10): 1694.
[46]
Yazici Y, McAlindon T E, Gibofsky A, Lane N E, Latterman C, Skrepnik N, Swearingen C J, DiFrancesco A, Tambiah J R, Hochberg M C. Osteoarthr. Cartil., 2019, 27: S503.
[47]
Lietman C, Wu B, Lechner S, Shinar A, Sehgal M, Rossomacha E, Datta P, Sharma A, Gandhi R, Kapoor M, Young P P. JCI Insight, 2018, 3(2): e96308.
[48]
Patel S, Homaei A, El-Seedi H R, Akhtar N. Biomed. Pharmacother., 2018, 105: 526.
[49]
Ben-Aderet L, Merquiol E, Fahham D, Kumar A, Reich E, Ben-Nun Y, Kandel L, Haze A, Liebergall M, Kosińska M K, Steinmeyer J, Turk B, Blum G, Dvir-Ginzberg M. Arthritis Res. Ther., 2015, 17(1): 69.
[50]
Hayami T, Zhuo Y, Wesolowski G A, Pickarski M, Duong L T. Bone, 2012, 50(6): 1250.
[51]
Lindström E, Rizoska B, Henderson I, Terelius Y, Jerling M, Edenius C, Grabowska U. J. Transl. Med., 2018, 16(1): 125.
[52]
Kumar S, Dare L, Vasko-Moser J A, James I E, Blake S M, Rickard D J, Hwang S M, Tomaszek T, Yamashita D S, Marquis R W, Oh H, Jeong J U, Veber D F, Gowen M, Lark M W, Stroup G. Bone, 2007, 40(1): 122.
[53]
Binkley N, Orwoll E, Chapurlat R, Langdahl B L, Scott B B, Giezek H, Santora A C. Osteoporos. Int., 2021, 32(1): 173.
[54]
Johnson K, Zhu S T, Tremblay M S, Payette J N, Wang J N, Bouchez L C, Meeusen S, Althage A, Cho C Y, Wu X, Schultz P G. Science, 2012, 336(6082): 717.
[55]
Johnson K A, Woods A K, Joseph S B, Chatterjee A K, Zhu S, Wisler J, Klyushnichenko V, Li J, Lotz M K, Tremblay M, Schultz P G. Osteoarthr. Cartil., 2020, 28: S518.
[56]
Jeon O H, Kim C, Laberge R M, Demaria M, Rathod S, Vasserot A P, Chung J W, Kim D H, Poon Y, David N, Baker D J, van Deursen J M, Campisi J, Elisseeff J H. Nat. Med., 2017, 23(6): 775.
[57]
Latourte A, Kloppenburg M, Richette P. Nat. Rev. Rheumatol., 2020, 16(12): 673.
[58]
Zheng W H, Feng Z H, You S B, Zhang H, Tao Z Y, Wang Q, Chen H, Wu Y S. Int. Immunopharmacol., 2017, 45: 135.
[59]
Chow Y Y, Chin K Y. Mediat. Inflamm., 2020, 2020: 8293921.
[60]
Wang Z Q, Huang J L, Zhou S R, Luo F T, Xu W, Wang Q, Tan Q Y chen L, Wang J, Chen H G, Chen L, Xie Y L, Du X L. J. Cell. Mol. Med., 2017, 21(12): 3231.
[61]
Liang S, Lv Z T, Zhang J M, Wang Y T, Dong Y H, Wang Z G, Chen K, Cheng P, Yang Q, Guo F J, Lu W W, Zhu W T, Chen A M. Front. Pharmacol., 2018, 9: 1378.
[62]
Wei Z, Sun X, Xu Q, Zhang Y, Tian F, Sun H, Zheng H, Dai J. Die Pharmazie, 2016, 71(10): 583.
[63]
Liu F C, Lu J W, Chien C Y, Huang H S, Lee C C, Lien S B, Lin L C, Chen L W, Ho Y J, Shen M C, Ho L J, Lai J H. Int. J. Mol. Sci., 2018, 19(5): 1453.
[64]
Pan D Y, Yin P, Li L K, Wu K L, Tong C G, Liu D P. Biochem. Biophys. Res. Commun., 2023, 657: 59.
[65]
Zhang Y, Lin Z, Chen D, He Y. Biochem. Biophys. Res. Commun., 2021, 553: 119.
[66]
Ahmad N, Ansari M Y, Haqqi T M. J. Cell. Physiol., 2020, 235(10): 6366.
[67]
Malfait A M, Schnitzer T J. Nat. Rev. Rheumatol., 2013, 9(11): 654.
[68]
Lane N E, Schnitzer T J, Birbara C A, Mokhtarani M, Shelton D L, Smith M D, Brown M T. N Engl J. Med., 2010, 363(16): 1521.
[69]
Caterina M J, Rosen T A, Tominaga M, Brake A J, Julius D. Nature, 1999, 398(6726): 436.
[70]
Watt F E, Blauwet M B, Fakhoury A, Jacobs H, Smulders R, Lane N E. Osteoarthr. Cartil., 2019, 27(11): 1590.
[71]
Stevens R M, Ervin J, Nezzer J, Nieves Y, Guedes K, Burges R, Hanson P D, Campbell J N. Arthritis Rheumatol., 2019, 71(9): 1524.
[72]
谢毓元, 陈文致. 化学通报, 1980, 5: 43.
[73]
谢毓元. 国外医学药学分册, 1984, 43.
[74]
Wang J B, Yang C H, Yan X M, Wu X H, Xie Y Y. Chin. Chem. Lett., 2005, 16(7): 859.
[75]
Xie Y L, Ding H S, Qian L H, Yan X M, Yang C H, Xie Y Y. Bioorg. Med. Chem. Lett., 2005, 15(13): 3267.
[76]
Ji Q G, Gao J, Wang J B, Yang C H, Hui X, Yan X M, Wu X H, Xie Y Y, Wang M W. Bioorg. Med. Chem. Lett., 2005, 15(11): 2891.
[77]
Yang C H, Xu G Y, Li J, Wu X H, Liu B, Yan X M, Wang M W, Xie Y Y. Bioorg. Med. Chem. Lett., 2005, 15(5): 1505.
[78]
Ning M, Zhou C, Weng J, Zhang S, Chen D, Yang C, Wang H, Ren J, Zhou L, Jin C, Wang M W. Br. J. Pharmacol., 2007, 150(1): 19.
[79]
Xu X, Qi X Y, Yan Y F, Qi J, Qian N D, Guo L, Li C W, Wang F, Huang P, Zhou H B, Jiang M, Yang C H, Deng L F. Eur. J. Med. Chem., 2016, 123: 769.
[80]
Jiang M, Wang T Q, Yan X M, Liu Z C, Yan Y F, Yang K, Qi J, Zhou H B, Qian N D, Zhou Q, Chen B, Xu X, Xi X B, Yang C H, Deng L F. J. Bone Miner. Res., 2019, 34(2): 361.
[81]
Jiang M, Peng L, Yang K, Wang T Q, Yan X M, Jiang T, Xu J R, Qi J, Zhou H B, Qian N D, Zhou Q, Chen B, Xu X, Deng L F, Yang C H. J. Med. Chem., 2019, 62(11): 5370.
[82]
Yang K, Li S Y, Wang T Q, Yan X M, He Q, Ning R N, Xu X, Yao W, Zhang X F, Yang C H, Jiang M, Deng L F. J. Med. Chem., 2022, 65(16): 10992.
[83]
Wang J, Wei W H, Zhang X F, Cao S Q, Hu B T, Ye Y, Jiang M, Wang T Q, Zuo J P, He S J, Yang C H. J. Med. Chem., 2021, 64(18): 13676.
[84]
Lin Z M, Xiang M, Wei W H, Fan S H, Chen L, Wang J, Yang X Q, Yang C H, He S J, Zuo J P. Science China Life Sciences, 2024. https://doi.org/10.1007/s11427-023-2587-2.
[85]
Anzini M, Di Capua A, Valenti S, Brogi S, Rovini M, Giuliani G, Cappelli A, Vomero S, Chiasserini L, Sega A, Poce G, Giorgi G, Calderone V, Martelli A, Testai L, Sautebin L, Rossi A, Pace S, Ghelardini C, Di Cesare Mannelli L, Benetti V, Giordani A, Anzellotti P, Dovizio M, Patrignani P, Biava M. J. Med. Chem., 2013, 56(8): 3191.
[86]
Yang T Y, Cao T T, Yang X G, Wang G L, Li Y L. Gene, 2024, 911: 148351.
PDF(2912 KB)

Accesses

Citation

Detail

Sections
Recommended

/