GMX1777
GMX1777 Uses, Dosage, Side Effects, Food Interaction and all others data.
GMX1777 is a water-soluble prodrug of the cyanoguanidine compound GMX1778 with potential antineoplastic activity. In vivo, apoptosis inducer GMX1777 is rapidly converted into GMX1778 through hydrolytic cleavage of a carbonate ester bond. Although the exact mechanism of action has yet to be fully elucidated, GMX1778 appears to antagonize nuclear factor-kappa B (NF-kB) transcription, resulting in the induction of tumor cell apoptosis.
GMX1777 exhibits unusually potent anti-tumor activity in preclinical animal models. The novel mechanism of action of GMX1778 supports the clinical use of GMX1777 as an anti-cancer agent. Moreover, the strong dependency of cancer cells on NAD+ to support DNA repair suggests a strong rationale for the use of GMX1777 in combination with DNA damaging agents for future trials.
| Trade Name | GMX1777 |
| Generic | GMX1777 |
| Type | |
| Groups | Investigational |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Intended for the treatment of solid tumors and lymphomas.
How GMX1777 works
The cytotoxicity of GMX1777, a prodrug of GMX1778, occurs exclusively through its ability to selectively inhibit nicotinamide phosphoribosyl transferase (NAMPRT). Tumor cells have elevated NAMPRT, an enzyme involved in the biosynthesis of oxidized nicotinamide adenine dinucleotide (NAD+). These cells have a high rate of NAD+ turnover due to elevated glycolysis and high ADP-ribosylation activity required for DNA repair, genome stability and telomere maintenance. These latter characteristics make cancer cells more susceptible to NAMPRT inhibition than normal cells. Although the mechanism of action of GMX1778 was initially believed to include NF-κB inhibition, a transcriptional factor that plays a role in cancer cell survival, NF-κB inhibition occurs as a consequence of ATP loss following NAMPRT inhibition and NAD+ decline.
Innovators Monograph
You find simplified version here GMX1777
