NAMPT Inhibitors: A Potential New Class Of Anti-Cancer Drugs



Nicotinamide phosphoribosyltransferase inhibitors are a new class of experimental cancer drugs that work by blocking an enzyme called nicotinamide phosphoribosyltransferase (NAMPT). NAMPT is an essential enzyme involved in the production of nicotinamide adenine dinucleotide (NAD+), an important cell signaling molecule and co-enzyme involved in energy production. Without adequate levels of NAD+, cancer cells cannot proliferate and survive.

 

By inhibiting NAMPT Inhibitors, these drugs aim to starve cancer cells of NAD+ and slow or stop tumor growth.


Several pharmaceutical companies are developing Nicotinamide phosphoribosyltransferase inhibitors for cancer treatment including:


- CHS-828 - developed by Calithera Biosciences. It is being tested in clinical trials for several tumor types including melanoma, renal cell carcinoma, triple-negative breast cancer, and hematological malignancies.


- GNE-617 - developed by Genentech. It is undergoing Phase I clinical trials for solid tumor cancers.


- GMX1778 - developed by Gem Pharmaceuticals. It has completed Phase I trials and is being tested in Phase II trials for acute myeloid leukemia.


How Do NAMPT Inhibitors Work?


Nicotinamide phosphoribosyltransferase inhibitors work by blocking the action of the NAMPT enzyme, which is the rate-limiting step in NAD+ biosynthesis from nicotinamide. Specifically, NAMPT catalyzes the reaction that converts nicotinamide to nicotinamide mononucleotide (NMN), which is further converted to NAD+. By inhibiting NAMPT, these drugs suppress NAD+ levels in cancer cells.


NAD+ serves as an important co-enzyme in many cellular processes essential for cancer cell survival, proliferation, and metabolism. It acts as an electron carrier in the citric acid cycle and electron transport chain during ATP production. It is also a substrate for sirtuin family proteins that regulate stress responses, DNA repair, and cell survival. low NAD+ levels induce metabolic and energetic stress that cancer cells cannot adapt to. This leads to dysfunction of NAD+-dependent processes and ultimately cell death.


Normal cells can compensate for lower NAD+ levels by other biosynthesis pathways. But cancer cells rely heavily on NAMPT-mediated NAD+ production due to their high metabolic and bioenergetic demands. Therefore, NAMPT inhibition preferentially targets cancer cells over normal cells.


Potential Advantages Of NAMPT Inhibitors


If proven effective in clinical trials, Nicotinamide phosphoribosyltransferase inhibitors could offer several potential advantages over existing cancer drugs:


- Novel mechanism of action - By targeting NAD+ biosynthesis, these drugs have a unique mode of action not addressed by other drug classes. This makes them attractive for use against cancers resistant to standard therapies.

 
- Broad anti-tumor activity - Preclinical studies show Nicotinamide phosphoribosyltransferase inhibitors can inhibit the proliferation of many different tumor cell lines as well as cancer stem cells. They may help treat a wide variety of solid and blood cancers.


- Synergistic with chemotherapy - Combining Nicotinamide phosphoribosyltransferase inhibitors with traditional DNA-damaging chemo drugs seems to make cancer cells more vulnerable to cell death. This broadens their potential use in combination regimens.


- Less toxic to normal cells - As normal cells can utilize alternate NAD+ production pathways, Nicotinamide phosphoribosyltransferase inhibitors seem to preferentially impact cancer cells minimally affecting healthy tissue. This may translate to a better side effect profile.


Ongoing Clinical Trials


Several clinical trials are ongoing to evaluate the safety, appropriate dosing, and efficacy of NAMPT inhibitors against different cancer types:


- CHS-828 in Phase I and Phase II trials for melanoma, renal cell carcinoma, triple-negative breast cancer, and leukemia.


- GNE-617 in Phase I trials as a monotherapy and in combination with chemotherapy for solid tumors.


- GMX1778 completed Phase I trials and ongoing Phase II trials in acute myeloid leukemia.

 
- FK-866 completed Phase I testing but further clinical development was halted due to formulation issues.


- Additional preclinical candidates are entering Phase I development from drug companies like O2Therapeutics.


Results from these early stage trials will provide important insights into optimum dosing, pharmacokinetics and pharmacodynamics of Nicotinamide phosphoribosyltransferase inhibitors. Later phase trials will evaluate their effectiveness in improving patient outcomes alone or in combination with other drugs.


By targeting the crucial NAD+ biosynthesis pathway, Nicotinamide phosphoribosyltransferase inhibitorsrepresent a promising new class of anti-cancer agents with potential applications in many tumor types. Ongoing clinical trials are testing their safety and efficacy profiles both as monotherapy and in combination regimens. If successful, NAMPT inhibitors become an important therapeutic option either alone or alongside standard chemotherapy or targeted therapies.

 

Get more insights on this topic: https://www.marketwebjournal.com/nampt-inhibitors-a-new-class-of-drugs-targeting-nad-biosynthesis/

Author Bio:

Alice Mutum is a seasoned senior content editor at Coherent Market Insights, leveraging extensive expertise gained from her previous role as a content writer. With seven years in content development, Alice masterfully employs SEO best practices and cutting-edge digital marketing strategies to craft high-ranking, impactful content. As an editor, she meticulously ensures flawless grammar and punctuation, precise data accuracy, and perfect alignment with audience needs in every research report. Alice's dedication to excellence and her strategic approach to content make her an invaluable asset in the world of market insights. (LinkedIn: www.linkedin.com/in/alice-mutum-3b247b137 )

*Note:
1. Source: Coherent Market Insights, Public sources, Desk research
2. We have leveraged AI tools to mine information and compile it

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