ADAMTS Inhibitor

Aldumastat (GLPG1972; S201086) is a potent, seletive and orally active ADAMTS-5 (IC₅₀=19 nM) inhibitor, and has 8-fold seletivity over ADAMTS-4 (IC₅₀=156 nM). Aldumastat has anticatabolic activity and is used for osteoarthritis research.

ADAMTS-5 Inhibitor is a potent ADAMTS-5 (aggrecanase-2) inhibitor, with an IC₅₀ of 1.1 µM. ADAMTS-5 Inhibitor shows >40-fold functional selectivity over ADAMTS-4 (aggrecanase-1).

ADAMTS-5-IN-3 (Example 37-2) is a potent inhibitor of ADAMTS-5 and ADAMTS-4 with IC₅₀s of 8 and 12 nM, respectively. ADAMTS-5-IN-3 can be used for the research of diseases involving degradation of cartilage or disruption of cartilage homeostasis, in particular osteoarthrosis and/or rheumatoid arthritis.

CRB0017 is a recombinant monoclonal antibody targeting ADAMTS5, with high affinity for the spacer domain of ADAMTS5 and strong antigen specificity. CRB0017 binds to the spacer domain of ADAMTS5 and reduces the proteolytic activity of this enzyme. CRB0017 delays articular cartilage degradation, alleviates the pathological severity of osteoarthritis, and decreases the osteoarthritis histopathological score. CRB0017 is applicable to the research of osteoarthritis.

GSK2394002 is an antibody inhibitor targeting ADAMTS-4 and ADAMTS-5, with cartilage-penetrating ability following systemic administration. GSK2394002 inhibits the release of aggrecan-derived neoepitopes and reduces cartilage degradation, exhibiting the potential to relieve pain, alleviate hyperalgesia and inhibit the progression of joint damage. GSK2394002 also induces potentially irreversible cardiovascular effects such as increased mean arterial pressure and myocardial ischemia in cynomolgus monkeys.

Isecarosmab (M-6495) is an anti-ADAMTS monoclonal antibody (mAb) with a K_D value of 3.65 pM. Isecarosmab has chondroprotective and anti-inflammatory activities. Isecarosmab can bind albumin to extend plasma half-life.

AGG-523 (PF-5212371) is an orally active, reversible, non-hydroxamate, zinc-binding selective inhibitor of ADAMTS4 and ADAMTS5 with IC₅₀ of <0.03 and 0.04 μM. AGG-523 also inhibits MMP-2, -8, 12 activity AGG-523 attenuates release of aggrecanase-generated ARG-aggrecan fragments into synovial fluid, reduces surgery-induced ARG-aggrecan release in rat joint models, and inhibits aggrecanase activity to slow cartilage degradation. AGG-523 can be used for the research of osteoarthritis.

Vicenin 3 is an angiotensin-converting enzyme (ACE) inhibitor (IC₅₀ = 46.91 μM) that can be isolated from the aerial parts of Desmodium styracifolium. Vicenin 3 ameliorates IL-1β-induced extracellular matrix degradation in SW1353 chondrocytes by regulating the MAPK pathway. Vicenin 3 can be used for the study of osteoarthritis (OA) and hypertension.

ADAMTS-5-IN-2 is an inhibitor of ADAMTS-5 (IC₅₀: 9.6 μM) and BoNT/A LC (IC₅₀: 0.71 μM). ADAMTS-5-IN-2 can be used in research related to botulism, osteoarthritis, and other conditions.

ADAMTS7-IN-1 (Compound 3a) is an effective and selective inhibitor of ADAMTS7 with a K_i value of 9 nM. ADAMTS7-IN-1 can be used in the research of atherosclerosis.

Adamtsostatin 16 is an anti-angiogenic 17-amino acid peptide containing type I thrombospondin motifs.

ZSNI-21 is a ADAM17/HDAC2 inhibitor with ADAM17 IC₅₀ 0.939 μM and HDAC2 IC₅₀ 0.844 μM. ZSNI-21 regulates the expression of apoptosis-related proteins (Bax, Bcl-2) and Cyclin D1, and induces apoptosis.. ZSNI-21 can be used for the research of hepatocellular carcinoma, breast cancer, and non-small cell lung cancer.

ADAMTS-5-IN-4 (Compound 4b) is a selective ADAMTS5 inhibitor with an IC₅₀ of 9.4 μM. ADAMTS-5-IN-4 significantly inhibits the degradation of Aggrecan in the implants of the osteoarthritis model. ADAMTS-5-IN-4 effectively inhibits the pseudopod elongation and directional migration of ovarian cancer cells. ADAMTS-5-IN-4 shows significant cytotoxicity to HEK293T cells, human chondrocytes, and porcine chondrocyte implants. ADAMTS-5-IN-4 can be used for the study of osteoarthritis and ovarian cancer.

Adamtsostatin 18 is an anti-angiogenic peptide derived from proteins containing type I thrombospondin motifs. Adamtsostatin 18 inhibits cell migration and proliferation.

Adamtsostatin 4 is an anti-angiogenic peptide. Adamtsostatin 4 can be used for the research of anti-angiogenic.

ADAMTS-4/5-IN-1 is an orally active, and selective dual ADAMTS-4/5 inhibitor with IC₅₀ values of 2 nM for human ADAMTS-4 and human ADAMTS-5, respectively. ADAMTS-4/5-IN-1 exhibits high selectivity against MMP enzymes. ADAMTS-4/5-IN-1 reduces aggrecan degradation products in synovial fluid. ADAMTS-4/5-IN-1 can be used for the research of osteoarthritis.