Inhibition of aggrecanases as a therapeutic strategy in osteoarthritis

The amelioration of cartilage degeneration by ADAMTS-5 inhibitor delivered in a hyaluronic acid hydrogel

(2014) Pengfei Chen et al.   BIOMATERIALS

Low Density Lipoprotein Receptor-related Protein 1 (LRP1)-mediated Endocytic Clearance of a Disintegrin and Metalloproteinase with Thrombospondin Motifs-4 (ADAMTS-4)

(2014) Kazuhiro Yamamoto et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

The hallmarks of osteoarthritis and the potential to develop personalised disease-modifying pharmacological therapeutics

(2014) D.P. Tonge et al.   OSTEOARTHRITIS AND CARTILAGE

A series of thiazole derivatives bearing thiazolidin-4-one as non-competitive ADAMTS-5 (aggrecanase-2) inhibitors

(2013) Masakazu Atobe et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Design, synthesis and SAR investigation of thienosultam derivatives as ADAMTS-5 (aggrecanase-2) inhibitors

(2013) Masakazu Atobe et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Aggrecanases in the human synovial fluid at different stages of osteoarthritis

(2013) Enshui Zhang et al.   CLINICAL RHEUMATOLOGY

Arylsulfonamide inhibitors of aggrecanases as potential therapeutic agents for osteoarthritis: Synthesis and biological evaluation

(2013) Elisa Nuti et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Aggrecanase-2 inhibitors based on the acylthiosemicarbazide zinc-binding group

(2013) Lucie Maingot et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Discovery of a benzimidazole series of ADAMTS-5 (aggrecanase-2) inhibitors by scaffold hopping

(2013) Shinya Sogame et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

New and emerging treatments for osteoarthritis management: will the dream come true with personalized medicine?

(2013) Camille Roubille et al.   EXPERT OPINION ON PHARMACOTHERAPY

ADAMTS proteoglycanases in the physiological and pathological central nervous system

(2013) Sighild Lemarchant et al.   Journal of Neuroinflammation

Targeting of ADAMTS5's ancillary domain with the recombinant mAb CRB0017 ameliorates disease progression in a spontaneous murine model of osteoarthritis

(2013) R. Chiusaroli et al.   OSTEOARTHRITIS AND CARTILAGE

Genetically Engineered Mouse Models Reveal the Importance of Proteases as Osteoarthritis Drug Targets

(2013) Rachel E. Miller et al.   Current Rheumatology Reports

Fragment-Based Approaches in Drug Discovery and Chemical Biology

(2012) Duncan E. Scott et al.   BIOCHEMISTRY

MMP-14 and MMP-2 are key metalloproteases in Dupuytren's disease fibroblast-mediated contraction

(2012) Janine M. Wilkinson et al.   BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

Rearranging Exosites in Noncatalytic Domains Can Redirect the Substrate Specificity of ADAMTS Proteases

(2012) Weiqiang Gao et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Novel Role of ADAMTS-5 Protein in Proteoglycan Turnover and Lipoprotein Retention in Atherosclerosis

(2012) Athanasios Didangelos et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Discovery of Highly Potent and Selective Small Molecule ADAMTS-5 Inhibitors That Inhibit Human Cartilage Degradation via Encoded Library Technology (ELT)

(2012) Hongfeng Deng et al.   JOURNAL OF MEDICINAL CHEMISTRY

Computational Insights into ADAMTS4, ADAMTS5 and MMP13 Inhibitor Selectivity

(2012) Federico Filomia et al.   Molecular Informatics

Approaches to discover non-ATP site kinase inhibitors

(2012) Lori Krim Gavrin et al.   MedChemComm

Aggrecan, an unusual polyelectrolyte: Review of solution behavior and physiological implications

(2011) Preethi L. Chandran et al.   Acta Biomaterialia

Orally active achiral N-hydroxyformamide inhibitors of ADAM-TS4 (aggrecanase-1) and ADAM-TS5 (aggrecanase-2) for the treatment of osteoarthritis

(2011) Chris De Savi et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Structure–activity study on a series of α-glutamic acid scaffold based compounds as new ADAMTS inhibitors

(2011) Lijie Peng et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Continued exploration of biphenylsulfonamide scaffold as a platform for aggrecanase-1 inhibition

(2011) Yonghan Hu et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Future therapeutics for osteoarthritis

(2011) Johanne Martel-Pelletier et al.   BONE

Discovery of (1S,2R,3R)-2,3-Dimethyl-2-phenyl-1-sulfamidocyclopropanecarboxylates: Novel and Highly Selective Aggrecanase Inhibitors

(2011) Makoto Shiozaki et al.   JOURNAL OF MEDICINAL CHEMISTRY

Structure analysis reveals the flexibility of the ADAMTS-5 active site

(2011) Huey-Sheng Shieh et al.   PROTEIN SCIENCE

Exploring Drug Target Flexibility Usingin SituClick Chemistry: Application to a Mycobacterial Transcriptional Regulator

(2010) Nicolas Willand et al.   ACS Chemical Biology

Cytokine-induced increases in ADAMTS-4 messenger RNA expression do not lead to increased aggrecanase activity in ADAMTS-5-deficient mice

(2010) Fraser M. Rogerson et al.   ARTHRITIS AND RHEUMATISM

New non-hydroxamic ADAMTS-5 inhibitors based on the 1,2,4-triazole-3-thiol scaffold

(2010) Lucie Maingot et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Design, Synthesis, and Preliminary Biological Evaluation of Pyrrolo[3,4-c]quinolin-1-one and Oxoisoindoline Derivatives as Aggrecanase Inhibitors

(2010) Andrea Cappelli et al.   ChemMedChem

Advances in the development of novel aggrecanase inhibitors

(2010) Adam M Gilbert et al.   EXPERT OPINION ON THERAPEUTIC PATENTS

Strategies for discovering and derisking covalent, irreversible enzyme inhibitors

(2010) Douglas S Johnson et al.   Future Medicinal Chemistry

MMPs are less efficient than ADAMTS5 in cleaving aggrecan core protein

(2010) Michaela Durigova et al.   MATRIX BIOLOGY

Identifying the human aggrecanase

(2010) A.J. Fosang et al.   OSTEOARTHRITIS AND CARTILAGE

Elevated aggrecanase activity in a rat model of joint injury is attenuated by an aggrecanase specific inhibitor

(2010) P.S. Chockalingam et al.   OSTEOARTHRITIS AND CARTILAGE

Hydroxamates: Relationships between Structure and Plasma Stability

(2009) Marion Flipo et al.   JOURNAL OF MEDICINAL CHEMISTRY

The C-terminal domains of ADAMTS-4 and ADAMTS-5 promote association with N-TIMP-3

(2009) Linda Troeberg et al.   MATRIX BIOLOGY

ADAMTS-5 deficient mice do not develop mechanical allodynia associated with osteoarthritis following medial meniscal destabilization

(2009) A.M. Malfait et al.   OSTEOARTHRITIS AND CARTILAGE

Specific targeting of metzincin family members with small-molecule inhibitors: Progress toward a multifarious challenge

(2008) Dimitris Georgiadis et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Synthesis of a 200-member library of squaric acid N-hydroxylamide amides

(2008) Julie Charton et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

N-((8-Hydroxy-5-substituted-quinolin-7-yl)(phenyl)methyl)-2-phenyloxy/amino-acetamide inhibitors of ADAMTS-5 (Aggrecanase-2)

(2008) Adam M. Gilbert et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

ADAMTS5−/− mice have less subchondral bone changes after induction of osteoarthritis through surgical instability: implications for a link between cartilage and subchondral bone changes

(2008) S.M. Botter et al.   OSTEOARTHRITIS AND CARTILAGE

Crystal structures of the two major aggrecan degrading enzymes, ADAMTS4 and ADAMTS5

(2007) Lidia Mosyak et al.   PROTEIN SCIENCE