Potent, selective, and orally bioavailable matrix metalloproteinase-13 inhibitors for the treatment of osteoarthritis

Hu, Yonghan; Xiang, Jason; DiGrandi, Martin J.; Du, Xiaona; Ipek, Manus; Laakso, Leif M.; Liu, Jianchang; Li, Wei; Rush, Thomas S.; Schmid, Jean; Skotnicki, Jerauld S.; Tam, Steve; Thomason, Jennifer R.; Wang, Qin; Levin, Jeremy I.

doi:10.1016/j.bmc.2005.07.076

Cited by 99 publications

(36 citation statements)

References 21 publications

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“…5 follow this same trend. By optimization of the benzoxazole substitution, selective MMP-13 (exemplified by 857081-53-9) [105] and aggrecanase ADAMTS [106] nM inhibitors were made. The γ -ketocarboxylate (second structure of this figure) is an MMP-2, -9 and -12 selective inhibitor (although only with μM potency) with efficacy in a hamster PPE-induced emphysema model [107].…”

Section: New Generation Hydroxamate-based Mmp Inhibitorsmentioning

confidence: 99%

Recent advances in MMP inhibitor design

Fisher

Mobashery

2006

Cancer Metastasis Rev

237

205

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The search for an MMP inhibitor with anticancer efficacy is a nearly three-decade endeavor. This inhibitor is yet to be found. The reasons for this failure include shortcomings in the chemistry of these compounds (including broad MMP sub-type selectivity, metabolic lability, and toxicity) as well as the emerging, and arguably extraordinary, complexity of MMP cell (and cancer) biology. Together these suggest that the successful anticancer inhibitor must possess MMP selectivity against the MMP subtype whose involvement is critical, yet highly temporally (with respect to metastatic progression) and mechanistically (with respect to matrix degradation) regulated. This review summarizes the progression of chemical structure and mechanistic thinking toward these objectives, with emphasis on the disappointment, the perseverance, and the resilient optimism that such an inhibitor is there to be discovered.

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Section: New Generation Hydroxamate-based Mmp Inhibitorsmentioning

confidence: 99%

Recent advances in MMP inhibitor design

Fisher

Mobashery

2006

Cancer Metastasis Rev

237

205

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“…The test articles are biphenyl sulfonamide carboxylic acid derivatives prepared in house at Wyeth Research laboratory with purity no less than 97% by HPLC assay (10,11). Protein binding for the test articles was determined by equilibrium dialysis methods.…”

Section: Test Articles and Materialsmentioning

confidence: 99%

In Vitro–In Vivo Correlation on Delivery of Drug Candidates to Articular Cartilage

Wang

Glasson²,

Raut³

et al. 2008

Pharm Res

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“…8 Benzofuran heterocycles show diverse range of pharmacological properties such as antibacterial, 9 antimicrobial, 10 antitumor 11 and antifungal 12 activities. They are also known to act as estrogen receptor (ER) ligands, 13 H 3 receptor antagonists, 14 selective ligands for the dopamine D3 receptor subtype, 15 metalloproteinase-13 inhibitors 16 and modulator of calcium level. 17 While isoindole and benzofuran derivatives have attracted significant attention over the years, the synthesis of spiroheterocyclic compounds containing both isoindole and benzofuran motifs has not been the subject of much research till now.…”

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confidence: 99%