Incyclinide (CMT-3) is a non-antibiotic matrix metalloproteinase (MMP) inhibitor derived from tetracycline[1]. Incyclinide inhibits tumor growth, metastasis, and angiogenesis by inducing apoptosis in cancer cells and degrading the extracellular matrix, without exhibiting antimicrobial activity[2]. Incyclinide is commonly used in research on Kaposi's sarcoma, solid tumors, and neurodegenerative diseases such as Parkinson's disease[3,4].
In vitro, Incyclinide (10, 20μM) treatment of HeLa cells for 24h inhibited the expression of NF-κB and Bcl-2 proteins and induced the cleavage of procaspase-9, caspase-3, and PARP[5]. Incyclinide (25μM) pretreatment of human CD34+ stem cell-derived mast cells for 1h, followed by anti-IgE stimulation for 1h, showed an inhibitory trend on IgE-mediated histamine release (inhibition rate of 31.1%)[6].
In vivo, Incyclinide (30mg/kg; once daily) was administered by oral gavage to Wistar rats fitted with orthodontic appliances for 14 days, significantly inhibiting orthodontic tooth displacement[7]. Incyclinide (200mg/kg; once daily) was administered by oral gavage to C3H/HeN mice intravaginally infected with Chlamydia muridarum for 21 days (from day 1 to day 21 post-infection), significantly reducing the incidence of pyosalpinx on days 14 and 21 post-infection[8].
References:
[1] Islam M M, Franco C D, Courtman D W, et al. A nonantibiotic chemically modified tetracycline (CMT-3) inhibits intimal thickening[J]. The American Journal of Pathology, 2003, 163(4): 1557-1566.
[2] Lokeshwar B L. MMP inhibition in prostate cancer[J]. Annals of the New York Academy of Sciences, 1999, 878(1): 271-289.
[3] Richards C, Pantanowitz L, Dezube B J. Antimicrobial and non-antimicrobial tetracyclines in human cancer trials[J]. Pharmacological Research, 2011, 63(2): 151-156.
[4] González-Lizárraga F, Ploper D, Ávila C L, et al. CMT-3 targets different α-synuclein aggregates mitigating their toxic and inflammogenic effects[J]. Scientific Reports, 2020, 10(1): 20258.
[5] Zhao L, Xu J, Yang Y, et al. Inhibitory impacts of chemically modified tetracycline-3 and underlying mechanism in human cervical cancer cells[J]. Anti-Cancer Drugs, 2013, 24(8): 799-809.
[6] Sandler C, Ekokoski E, Lindstedt K A, et al. Chemically modified tetracycline (CMT)-3 inhibits histamine release and cytokine production in mast cells: possible involvement of protein kinase C[J]. Inflammation Research, 2005, 54(7): 304-312.
[7] Bildt M M, Henneman S, Maltha J C, et al. CMT-3 inhibits orthodontic tooth displacement in the rat[J]. Archives of Oral Biology, 2007, 52(6): 571-578.
[8] Imtiaz M T, Schripsema J H, Sigar I M, et al. Inhibition of matrix metalloproteinases protects mice from ascending infection and chronic disease manifestations resulting from urogenital Chlamydia muridarum infection[J]. Infection and Immunity, 2006, 74(10): 5513-5521.
Incyclinide (CMT-3)是一种非抗生素，由四环素衍生的基质金属蛋白酶（MMP）抑制剂[1]。Incyclinide通过诱导癌细胞细胞凋亡和基质降解，可抑制肿瘤生长、转移和血管新生，且不具抗菌活性[2]。Incyclinide通常用于卡波西肉瘤和实体肿瘤，以及帕金森病等神经退行性疾病的研究[3,4]。
在体外，Incyclinide（10, 20μM）处理HeLa细胞24h，抑制了NF-κB和Bcl-2蛋白表达，激活了procaspase-9、caspase-3和PARP的裂解[5]。Incyclinide（25μM）预处理人CD34+干细胞来源的肥大细胞1h，再用anti-lgE刺激1h，对lgE介导的组胺释放显示出抑制趋势（抑制率31.1%）[6]。
在体内，Incyclinide（30mg/kg; once daily）通过口服灌胃给药佩戴正畸装置的Wistar大鼠14天，显著抑制了正畸牙齿的移动[7]。Incyclinide（200mg/kg; once daily）通过灌胃给药于Chlamydia muridarum阴道感染的C3H/HeN小鼠21天（感染后第1天至第21天连续给药），在感染后第14天和第21天显著减少了输卵管积脓的发生率[8]。