Incyclinide

• CAT Number: M131833
• CAS Number: 15866-90-7
• Molecular Formula: C₁₉H₁₇NO₇
• Molecular Weight: 371.34
• Purity: ≥95%
• Target: MMP
• Storage: -20°C
• IUPAC Name: (4aS,5aR,12aR)-1,10,11,12a-tetrahydroxy-3,12-dioxo-4a,5,5a,6-tetrahydro-4H-tetracene-2-carboxamide
• InChI: InChI=1S/C19H17NO7/c20-18(26)14-11(22)6-9-5-8-4-7-2-1-3-10(21)12(7)15(23)13(8)16(24)19(9,27)17(14)25/h1-3,8-9,21,23,25,27H,4-6H2,(H2,20,26)/t8-,9-,19-/m0/s1
• InChIKey: NBRQRXRBIHVLGI-OWXODZSWSA-N
• SMILES: C1C2CC3=C(C(=CC=C3)O)C(=C2C(=O)C4(C1CC(=O)C(=C4O)C(=O)N)O)O

Iincyclinide (Cat.No:M131833), also known as CMT-3 and COL-3, is a MMP inhibitor and a chemically-modified tetracycline with potential antineoplastic activity. Incyclinide inhibits matrix metalloproteinases (MMPs), thereby inducing extracellular matrix degradation, and inhibiting angiogenesis, tumor growth and invasion, and metastasis. This agent also causes mitochondrial depolarization in tumor cells and induces both cellular apoptosis and tissue necrosis.

Reference

1: Edan RA, Luqmani YA, Masocha W. COL-3, a chemically modified tetracycline, inhibits lipopolysaccharide-induced microglia activation and cytokine expression in the brain. PLoS One. 2013;8(2):e57827. doi: 10.1371/journal.pone.0057827. Epub 2013 Feb 28. PubMed PMID: 23469077; PubMed Central PMCID: PMC3585197.
2: Parvathy SS, Masocha W. Matrix metalloproteinase inhibitor COL-3 prevents the development of paclitaxel-induced hyperalgesia in mice. Med Princ Pract. 2013;22(1):35-41. doi: 10.1159/000341710. Epub 2012 Aug 16. PubMed PMID: 22907189.
3: Rudek MA, New P, Mikkelsen T, Phuphanich S, Alavi JB, Nabors LB, Piantadosi S, Fisher JD, Grossman SA. Phase I and pharmacokinetic study of COL-3 in patients with recurrent high-grade gliomas. J Neurooncol. 2011 Nov;105(2):375-81. doi: 10.1007/s11060-011-0602-9. Epub 2011 May 6. PubMed PMID: 21547395; PubMed Central PMCID: PMC3197967.
4: Chu QS, Forouzesh B, Syed S, Mita M, Schwartz G, Cooper J, Curtright J, Rowinsky EK. A phase II and pharmacological study of the matrix metalloproteinase inhibitor (MMPI) COL-3 in patients with advanced soft tissue sarcomas. Invest New Drugs. 2007 Aug;25(4):359-67. Epub 2007 Jan 20. Erratum in: Invest New Drugs. 2007 Aug;25(4):357. Copper, Joshua [corrected to Cooper, Joshua]. PubMed PMID: 17237909.
5: Halter JM, Pavone LA, Steinberg JM, Gatto LA, DiRocco J, Landas S, Nieman GF. Chemically modified tetracycline (COL-3) improves survival if given 12 but not 24 hours after cecal ligation and puncture. Shock. 2006 Dec;26(6):587-91. PubMed PMID: 17117134.
6: Muir P, Manley PA, Hao Z. COL-3 inhibition of collagen fragmentation in ruptured cranial cruciate ligament explants from dogs with stifle arthritis. Vet J. 2007 Sep;174(2):403-6. Epub 2006 Sep 15. PubMed PMID: 16978892.
7: Furlow B. COL-3 benefits patients with AIDS-related Kaposi/'s sarcoma. Lancet Oncol. 2006 May;7(5):368. PubMed PMID: 16696161.
8: Dezube BJ, Krown SE, Lee JY, Bauer KS, Aboulafia DM. Randomized phase II trial of matrix metalloproteinase inhibitor COL-3 in AIDS-related Kaposi/'s sarcoma: an AIDS Malignancy Consortium Study. J Clin Oncol. 2006 Mar 20;24(9):1389-94. PubMed PMID: 16549833.
9: Onoda T, Ono T, Dhar DK, Yamanoi A, Nagasue N. Tetracycline analogues (doxycycline and COL-3) induce caspase-dependent and -independent apoptosis in human colon cancer cells. Int J Cancer. 2006 Mar 1;118(5):1309-15. PubMed PMID: 16152604.
10: Li J, Zhou S, Huynh H, Duan W, Chan E. Alteration of the pharmacokinetics of COL-3, a matrix metalloproteinase inhibitor, due to acute gastrointestinal toxicity of doxorubicin. Pharm Res. 2005 Nov;22(11):1954-63. Epub 2005 Aug 13. PubMed PMID: 16086226.
11: Li J, Zhou S, Huynh H, Chan E. Significant intestinal excretion, one source of variability in pharmacokinetics of COL-3, a chemically modified tetracycline. Pharm Res. 2005 Mar;22(3):397-404. PubMed PMID: 15835745.
12: Rudek MA, Hartke C, Zabelina Y, Zhao M, New P, Baker SD. A sensitive method for determination of COL-3, a chemically modified tetracycline, in human plasma using high-performance liquid chromatography and ultraviolet detection. J Pharm Biomed Anal. 2005 Apr 1;37(4):751-6. Epub 2004 Dec 29. PubMed PMID: 15797797.
13: Syed S, Takimoto C, Hidalgo M, Rizzo J, Kuhn JG, Hammond LA, Schwartz G, Tolcher A, Patnaik A, Eckhardt SG, Rowinsky EK. A phase I and pharmacokinetic study of Col-3 (Metastat), an oral tetracycline derivative with potent matrix metalloproteinase and antitumor properties. Clin Cancer Res. 2004 Oct 1;10(19):6512-21. PubMed PMID: 15475438.
14: Li J, Huynh H, Chan E. Reversed-phase liquid chromatography method to determine COL-3, a matrix metalloproteinase inhibitor, in biological samples. J Chromatogr B Analyt Technol Biomed Life Sci. 2004 Jan 25;799(2):311-21. PubMed PMID: 14670750.
15: Rudek MA, Venitz J, Ando Y, Reed E, Pluda JM, Figg WD. Factors involved in the pharmacokinetics of COL-3, a matrix metalloproteinase inhibitor, in patients with refractory metastatic cancer: clinical and experimental studies. J Clin Pharmacol. 2003 Oct;43(10):1124-35. PubMed PMID: 14517195.
16: Chen YL, Hanson GD, Weng N, Powala C, Zerler B. Quantification of 6-deoxy-6-demethyl-4-dedimethylaminotetracycline (COL-3) in human plasma using liquid chromatography coupled with electrospray ionization tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2003 Aug 25;794(1):77-88. PubMed PMID: 12888200.
17: Li J, Huynh H, Chan E. Evidence for dissolution rate-limited absorption of COL-3, a matrix metalloproteinase inhibitor, leading to the irregular absorption profile in rats after oral administration. Pharm Res. 2002 Nov;19(11):1655-62. PubMed PMID: 12458671.
18: Lokeshwar BL, Selzer MG, Zhu BQ, Block NL, Golub LM. Inhibition of cell proliferation, invasion, tumor growth and metastasis by an oral non-antimicrobial tetracycline analog (COL-3) in a metastatic prostate cancer model. Int J Cancer. 2002 Mar 10;98(2):297-309. PubMed PMID: 11857423.
19: Cianfrocca M, Cooley TP, Lee JY, Rudek MA, Scadden DT, Ratner L, Pluda JM, Figg WD, Krown SE, Dezube BJ. Matrix metalloproteinase inhibitor COL-3 in the treatment of AIDS-related Kaposi/'s sarcoma: a phase I AIDS malignancy consortium study. J Clin Oncol. 2002 Jan 1;20(1):153-9. PubMed PMID: 11773164.
20: Ghate JV, Turner ML, Rudek MA, Figg WD, Dahut W, Dyer V, Pluda JM, Reed E. Drug-induced lupus associated with COL-3: report of 3 cases. Arch Dermatol. 2001 Apr;137(4):471-4. PubMed PMID: 11295928.