Table 2.

Mechanism of action, clinical outcomes and toxicities of compounds inhibiting MMP-9 expression and/or activity.

Drug	Class	Mechanism of Action	Clinical Outcomes	Toxicities
MARIMASTAT	Broad-spectrum MMPI	Chelates MMP catalytic zinc	Does not improve OS of glioblastoma, NSCLC and pancreatic or colorectal ca pts [138]	Musculoskeletal pain [138]
TANOMASTAT	Narrow-spectrum MMPI	Binds MMP exosite	Does not improve OS of NSCLC, pancreatic or ovarian ca pts [139]	Nausea, vomiting [139]
CURCUMIN	Plant extract	Reduces MMP-9 expression	Improves the efficacy of chemotherapy in prostate ca pts [140]	None [140]
ANDECALIXIMAB	Humanized mAB	Neutralizes MMP-9	Improves OS and reduces tumor size in gastric ca pts [141]	Nausea, vomiting, fatigue [141]
DOXYCYCLINE	Antibiotic	Reduces MMP-9 expression	Does not improve OS of breast ca pts [142]	Nausea, vomiting, diarrhea [142]
LPV-RTV	HIV-PI	Inhibits the AKT-MMP-9 pathway	effective against CIN [143]	Increase in glycaemia and/or lipemia [144,145]
AZT	HIV-RTI	Reduces MMP-9 expression	Improves the efficacy of chemotherapy in T cell leukemia pts [146]	Headache, nausea, vomiting, neutropenia, anemia, hepatotoxicity, myopathy [147]
AMD3100	CXCR4 antagonist	Inhibits the CXCL12-AKT-MMP-9 pathway	Effective against hematological malignancies [148,149]	Musculoskeletal pain, gastrointestinal disturbances [150]

Here, we summarize the biological and clinical effects of MMP-9 antagonists approved for therapeutic use in humans. The table shows the activities of a drug selected (because of its ability to effectively antagonizr MMP-9) for each of the following chemical-pharmacological classes: broad or narrow-spectrum synthetic MMP inhibitors, plant extracts, anti-MMP-9 antibodies, antibiotics, chemokine receptor antagonists, and inhibitors of the HIV-protease or reverse transcriptase. Abbreviations: AKT, protein kinase B; AZT, zidovudine; ca, carcinoma; CIN, cervical intraepithelial neoplasia; CXCL, CXC chemokine ligand; CXCR, CXC chemokine receptor; HIV, human immunodeficiency virus; LPV, lopinavir; mAB, monoclonal antibody; MMP, matrix metalloproteinase; MMPI, matrix metalloproteinase inhibitor; NSCLC, nonsmall cell lung carcinoma; OS, overall survival; PI, protease inhibitor; pts, patients; RTI, reverse transcriptase inhibitor; RTV, ritonavir. References with specific information are given in square brackets.