MedKoo product information:

Teglarinad chloride

Teglarinad chloride is a water-soluble prodrug of a cyanoguanidine compound with potential antineoplastic activity. In vivo, teglarinad chloride is rapidly converted into active drug through hydrolytic cleavage of a carbonate ester bond. Although the exact mechanism of action has yet to be fully elucidated, the active drug appears to antagonize nuclear factor-kappa B (NF-kB) transcription, resulting in the induction of tumor cell apoptosis. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus).

GMX1777 is a water-soluble intravenously administered prodrug of GMX1778 that Gemin X in-licensed from LEO Pharma (LEO numbers: EB1627 and CHS828, respectively). GMX1777 has been shown to inhibit NAD+ synthesis in cancer cells and has demonstrated a broad spectrum of antitumor activity in human xenograft models. GMX1777 has patent protection through to 2022.  (Source: http://www.geminx.com/en/research/gmx1777.php).

IC50 values of GMX1777 for FaDu and C666-1 cells were 10 and 5 nmol/L, respectively, which interacted synergistically with radiotherapy. GMX1777 induced a rapid decline in intracellular NAD+ followed by ATP reduction associated with significant cytotoxicity.  GMX1777 plus radiotherapy is an effective therapeutic strategy for head and neck cancer, mediated via pleiotropic effects of inhibition of DNA repair and tumor angiogenesis, while sparing normal tissues. Therefore, GMX1777 combined with radiotherapy definitely warrants clinical evaluation in human head and neck cancer patients. (Source: Clin Cancer Res; 2010, 16(3); 898–911 or http://clincancerres.aacrjournals.org/content/16/3/898.abstract).

Current developer:    Gemin X Pharmaceuticals.

1: Fuchs D, Rodriguez A, Eriksson S, Christofferson R, Sundberg C, Azarbayjani F. Metronomic administration of the drug GMX1777, a cellular NAD synthesis inhibitor, results in neuroblastoma regression and vessel maturation without inducing drug resistance. Int J Cancer. 2010 Jun 15;126(12):2773-89. PubMed PMID: 20112275.

2: Kato H, Ito E, Shi W, Alajez NM, Yue S, Lee C, Chan N, Bhogal N, Coackley CL,  Vines D, Green D, Waldron J, Gullane P, Bristow R, Liu FF. Efficacy of combining GMX1777 with radiation therapy for human head and neck carcinoma. Clin Cancer Res. 2010 Feb 1;16(3):898-911. Epub 2010 Jan 26. PubMed PMID: 20103674.

3: Beauparlant P, Bédard D, Bernier C, Chan H, Gilbert K, Goulet D, Gratton MO, Lavoie M, Roulston A, Turcotte E, Watson M. Preclinical development of the nicotinamide phosphoribosyl transferase inhibitor prodrug GMX1777. Anticancer Drugs. 2009 Jun;20(5):346-54. PubMed PMID: 19369827.