ADAMTS-5 Inhibitor
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MedKoo CAT#: 561427

CAS#: 929634-33-3

Description: ADAMTS-5 Inhibitor is an inhibitor of ADAMTS-5 (aggrecanase-2; IC50 = 1.1 µM) with 40-fold selectivity over ADAMTS-4 (aggrecanase-1). ADAMTS-5 has key roles in cartilage destruction associated with osteoarthritis and is also involved in other pathways, including neurological processes.

Chemical Structure

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ADAMTS-5 Inhibitor
CAS# 929634-33-3
Instruction

Theoretical Analysis

MedKoo Cat#: 561427
Name: ADAMTS-5 Inhibitor
CAS#: 929634-33-3
Chemical Formula: C16H11ClF3N3OS3
Exact Mass: 448.97
Molecular Weight: 449.910
Elemental Analysis: C, 42.71; H, 2.46; Cl, 7.88; F, 12.67; N, 9.34; O, 3.56; S, 21.38

Price and Availability

Size Price Availability Quantity
5mg USD 330 2 Weeks
25mg USD 975 2 Weeks
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Synonym: ADAMTS-5 Inhibitor; ADAMTS 5 Inhibitor; ADAMTS5 Inhibitor;

IUPAC/Chemical Name: (5Z)-5-[[5-[(4-Chlorophenyl)methylsulfanyl]-1-methyl-3-(trifluoromethyl)pyrazol-4-yl]methylidene]-2-sulfanylidene-1,3-thiazolidin-4-one

InChi Key: CVYPRDPBCXSVBN-WDZFZDKYSA-N

InChi Code: InChI=1S/C16H11ClF3N3OS3/c1-23-14(26-7-8-2-4-9(17)5-3-8)10(12(22-23)16(18,19)20)6-11-13(24)21-15(25)27-11/h2-6H,7H2,1H3,(H,21,24,25)/b11-6-

SMILES Code: O=C1NC(S/C1=C\C2=C(SCC3=CC=C(Cl)C=C3)N(C)N=C2C(F)(F)F)=S

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info:

Biological target:
In vitro activity:
In vivo activity:

Preparing Stock Solutions

The following data is based on the product molecular weight 449.91 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
In vitro protocol:
In vivo protocol:

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1: Wang T, He C. Pro-inflammatory cytokines: The link between obesity and osteoarthritis. Cytokine Growth Factor Rev. 2018 Dec;44:38-50. doi: 10.1016/j.cytogfr.2018.10.002. Epub 2018 Oct 11. PMID: 30340925.


2: Malemud CJ. Inhibition of MMPs and ADAM/ADAMTS. Biochem Pharmacol. 2019 Jul;165:33-40. doi: 10.1016/j.bcp.2019.02.033. Epub 2019 Feb 28. PMID: 30826330; PMCID: PMC6557692.


3: Latourte A, Richette P. Inhibition of ADAMTS-5: the right target for osteoarthritis? Osteoarthritis Cartilage. 2022 Feb;30(2):175-177. doi: 10.1016/j.joca.2021.09.012. Epub 2021 Oct 6. PMID: 34624506.


4: Santamaria S. ADAMTS-5: A difficult teenager turning 20. Int J Exp Pathol. 2020 Feb;101(1-2):4-20. doi: 10.1111/iep.12344. Epub 2020 Mar 27. PMID: 32219922; PMCID: PMC7306899.


5: Santamaria S, Cuffaro D, Nuti E, Ciccone L, Tuccinardi T, Liva F, D'Andrea F, de Groot R, Rossello A, Ahnström J. Exosite inhibition of ADAMTS-5 by a glycoconjugated arylsulfonamide. Sci Rep. 2021 Jan 13;11(1):949. doi: 10.1038/s41598-020-80294-1. PMID: 33441904; PMCID: PMC7806935.


6: Papathanasiou I, Trachana V, Mourmoura E, Tsezou A. DNA methylation regulates miR-140-5p and miR-146a expression in osteoarthritis. Life Sci. 2019 Jul 1;228:274-284. doi: 10.1016/j.lfs.2019.05.018. Epub 2019 May 9. PMID: 31077718.


7: Brebion F, Gosmini R, Deprez P, Varin M, Peixoto C, Alvey L, Jary H, Bienvenu N, Triballeau N, Blanque R, Cottereaux C, Christophe T, Vandervoort N, Mollat P, Touitou R, Leonard P, De Ceuninck F, Botez I, Monjardet A, van der Aar E, Amantini D. Discovery of GLPG1972/S201086, a Potent, Selective, and Orally Bioavailable ADAMTS-5 Inhibitor for the Treatment of Osteoarthritis. J Med Chem. 2021 Mar 25;64(6):2937-2952. doi: 10.1021/acs.jmedchem.0c02008. Epub 2021 Mar 15. PMID: 33719441.


8: van der Aar E, Deckx H, Dupont S, Fieuw A, Delage S, Larsson S, Struglics A, Lohmander LS, Lalande A, Leroux E, Amantini D, Passier P. Safety, Pharmacokinetics, and Pharmacodynamics of the ADAMTS-5 Inhibitor GLPG1972/S201086 in Healthy Volunteers and Participants With Osteoarthritis of the Knee or Hip. Clin Pharmacol Drug Dev. 2022 Jan;11(1):112-122. doi: 10.1002/cpdd.1042. Epub 2021 Dec 2. PMID: 34859612; PMCID: PMC9299907.


9: Cui Z, Crane J, Xie H, Jin X, Zhen G, Li C, Xie L, Wang L, Bian Q, Qiu T, Wan M, Xie M, Ding S, Yu B, Cao X. Halofuginone attenuates osteoarthritis by inhibition of TGF-β activity and H-type vessel formation in subchondral bone. Ann Rheum Dis. 2016 Sep;75(9):1714-21. doi: 10.1136/annrheumdis-2015-207923. Epub 2015 Oct 15. PMID: 26470720; PMCID: PMC5013081.


10: Fosang AJ. ADAMTS-5 takes centre stage in new developments for aggrecanase inhibitors. Osteoarthritis Cartilage. 2015 Aug;23(8):1231-2. doi: 10.1016/j.joca.2015.05.023. Epub 2015 May 28. PMID: 26028137.


11: Scavenius C, Poulsen EC, Thøgersen IB, Roebuck M, Frostick S, Bou-Gharios G, Yamamoto K, Deleuran B, Enghild JJ. Matrix-degrading protease ADAMTS-5 cleaves inter-α-inhibitor and releases active heavy chain 2 in synovial fluids from arthritic patients. J Biol Chem. 2019 Oct 18;294(42):15495-15504. doi: 10.1074/jbc.RA119.008844. Epub 2019 Sep 4. PMID: 31484722; PMCID: PMC6802519.


12: Latourte A, Cherifi C, Maillet J, Ea HK, Bouaziz W, Funck-Brentano T, Cohen- Solal M, Hay E, Richette P. Systemic inhibition of IL-6/Stat3 signalling protects against experimental osteoarthritis. Ann Rheum Dis. 2017 Apr;76(4):748-755. doi: 10.1136/annrheumdis-2016-209757. Epub 2016 Oct 27. PMID: 27789465.


13: Chen P, Zhu S, Wang Y, Mu Q, Wu Y, Xia Q, Zhang X, Sun H, Tao J, Hu H, Lu P, Ouyang H. The amelioration of cartilage degeneration by ADAMTS-5 inhibitor delivered in a hyaluronic acid hydrogel. Biomaterials. 2014 Mar;35(9):2827-36. doi: 10.1016/j.biomaterials.2013.12.076. Epub 2014 Jan 11. PMID: 24424207.


14: Turner SL, Mangnall D, Bird NC, Bunning RA, Blair-Zajdel ME. Expression of ADAMTS-1, ADAMTS-4, ADAMTS-5 and TIMP3 by hepatocellular carcinoma cell lines. Int J Oncol. 2012 Sep;41(3):1043-9. doi: 10.3892/ijo.2012.1525. Epub 2012 Jun 20. PMID: 22735305.


15: Tortorella MD, Arner EC, Hills R, Easton A, Korte-Sarfaty J, Fok K, Wittwer AJ, Liu RQ, Malfait AM. Alpha2-macroglobulin is a novel substrate for ADAMTS-4 and ADAMTS-5 and represents an endogenous inhibitor of these enzymes. J Biol Chem. 2004 Apr 23;279(17):17554-61. doi: 10.1074/jbc.M313041200. Epub 2004 Jan 7. PMID: 14715656.


16: Gilbert AM, Bursavich MG, Lombardi S, Georgiadis KE, Reifenberg E, Flannery CR, Morris EA. 5-((1H-pyrazol-4-yl)methylene)-2-thioxothiazolidin-4-one inhibitors of ADAMTS-5. Bioorg Med Chem Lett. 2007 Mar 1;17(5):1189-92. doi: 10.1016/j.bmcl.2006.12.020. Epub 2006 Dec 12. PMID: 17210252.


17: Zhao Y, Li A. miR-19b-3p relieves intervertebral disc degeneration through modulating PTEN/PI3K/Akt/mTOR signaling pathway. Aging (Albany NY). 2021 Sep 23;13(18):22459-22473. doi: 10.18632/aging.203553. Epub 2021 Sep 23. PMID: 34554926; PMCID: PMC8507280.


18: Imbert O, Deckx H, Bernard K, van der Aar E, Pueyo M, Saeed N, Fuerst T, Wirth W, Conaghan PG, Eckstein F. The design of a randomized, placebo- controlled, dose-ranging trial to investigate the efficacy and safety of the ADAMTS-5 inhibitor S201086/GLPG1972 in knee osteoarthritis. Osteoarthr Cartil Open. 2021 Aug 16;3(4):100209. doi: 10.1016/j.ocarto.2021.100209. PMID: 36474770; PMCID: PMC9718074.


19: Siebuhr AS, Werkmann D, Bay-Jensen AC, Thudium CS, Karsdal MA, Serruys B, Ladel C, Michaelis M, Lindemann S. The Anti-ADAMTS-5 Nanobody® M6495 Protects Cartilage Degradation Ex Vivo. Int J Mol Sci. 2020 Aug 20;21(17):5992. doi: 10.3390/ijms21175992. PMID: 32825512; PMCID: PMC7503673.


20: Kosasih HJ, Last K, Rogerson FM, Golub SB, Gauci SJ, Russo VC, Stanton H, Wilson R, Lamande SR, Holden P, Fosang AJ. A Disintegrin and Metalloproteinase with Thrombospondin Motifs-5 (ADAMTS-5) Forms Catalytically Active Oligomers. J Biol Chem. 2016 Feb 12;291(7):3197-208. doi: 10.1074/jbc.M115.704817. Epub 2015 Dec 14. PMID: 26668318; PMCID: PMC4751368.