Incyclinide (CMT-3) (Synonyms: CMT-3, COL-3, NSC 683551)

Incyclinide (CMT-3, COL-3) is a matrix metalloproteinase (MMP) inhibitor, thereby inducing extracellular matrix degradation, and inhibiting angiogenesis, tumor growth and invasion, and metastasis.

Incyclinide has been shown to experimentally suppress prostate cancer, colon adenocarcinoma and melanoma invasiveness in cell culture. Adding incyclinide at final concentrations of 5 to 20 μM inhibits MT1-MMP gelatinolytic and caseinolytic activity, blocks MT1-MMPactivation of pro-MMP-2, and decreases invasiveness of HT-1080 fibrosarcoma cells[1]. Incyclinide is an especially effective inhibitor of the growth and viability of filamentous fungi. Most of the MICs of CMT-3 against filamentous fungi are found to be between 0.25 and 8 μg/mL, and the inhibition of viability of these fungi by incyclinide is routinely higher than 90%[2].

Incyclinide inhibits tooth movement in the rat, probably by reducing the number of osteoclasts at the compression side. This might be due to induction of apoptosis in activated osteoclasts or reduced osteoclast migration. Reduced MMP activity by incyclinide might also directly inhibit degradation of the organic bone matrix[3].

[1]. Lee HM, et al. CMT-3, a non-antimicrobial tetracycline (TC), inhibits MT1-MMPactivity: relevance to cancer. Curr Med Chem. 2001 Feb;8(3):257-60. [2]. Liu Y, A chemically modified tetracycline (CMT-3) is a new antifungal agent. Antimicrob Agents Chemother. 2002 May;46(5):1447-54. [3]. Bildt MM, et al. CMT-3 inhibits orthodontic tooth displacement in the rat. Arch Oral Biol. 2007 Jun;52(6):571-8.