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Last update 08 May 2025

IDH1 x NAMPT

Last update 08 May 2025

Basic Info

Related Targets

IDH1NAMPT

Drugs associated with IDH1 x NAMPT

NAMPT inhibitors(China Pharmaceutical University)

Target

IDH1 x NAMPT

Mechanism

IDH1 inhibitors [+1]

Active Org.

China Pharmaceutical University

Originator Org.

China Pharmaceutical University

Active Indication

Glioma

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with IDH1 x NAMPT

100 Translational Medicine associated with IDH1 x NAMPT

0 Patents (Medical) associated with IDH1 x NAMPT

Literatures (Medical) associated with IDH1 x NAMPT

13 Jun 2024·Journal of Medicinal Chemistry

Discovery of Novel Dual Inhibitors Targeting Mutant IDH1 and NAMPT for the Treatment of Glioma with IDH1Mutation

Article

Author: Ma, Tianfang ; Li, Chunzheng ; Gui, Gang ; Qin, Anqi ; Wang, Xiaoyu ; Wen, Fei ; Zha, Xiaoming ; Chen, Hui

The targeting of cancer cell intrinsic metabolism has emerged as a promising strategy for antitumor intervention. In the study, we identified the first-in-class small molecules that effectively inhibit both mutant isocitrate dehydrogenase 1 (mIDH1) and nicotinamide phosphoribosyltransferase (NAMPT), two crucial targets in cancer metabolism, through structure-based drug design. Notably, compound 23h exhibits excellent and balanced inhibitory activities against both mIDH1 (IC₅₀ = 14.93 nM) and NAMPT (IC₅₀ = 12.56 nM), leading to significant suppression of IDH1-mutated glioma cell (U87 MG-IDH1^R132H) proliferation. Significantly, compound 23h has the ability to cross the blood-brain barrier (B/P ratio, 0.76) and demonstrates remarkable in vivo antitumor efficacy (20 mg/kg) in the U87 MG-IDH1^R132H orthotopic transplantation mouse models without any notable toxicity. This proof-of-concept investigation substantiates the viability of discovering small molecules that concurrently target mIDH1 and NAMPT, providing valuable leads for the treatment of glioma and an efficient approach for the discovery of multitarget antitumor drugs.

01 Jan 2021·Free Radical Biology and MedicineQ2 · MEDICINE

NAD+ depletion radiosensitizes 2-DG-treated glioma cells by abolishing metabolic adaptation

Q2 · MEDICINE

Article

Author: Yu, Jiahua ; Zhang, Haowen ; Wang, Zhongmin ; Wang, Chen ; Zhang, Wei ; Yin, Narui ; Shi, Xiaolin ; Gu, Cheng ; Liu, Fenju ; Ren, Huangge

Two-deoxy-d-glucose (2-DG) mediated glucose restriction (GR) has been applied as a potential therapeutic strategy for tumor clinical treatments. However, increasing evidences have indicated that 2-DG alone is inefficient in killing tumor cells, and the effect of 2-DG on modifying tumor radio-responses also remains controversial. In this study, we found that 2-DG triggered metabolic adaption in U87 glioma cells by up-regulating nicotinamide phosphoribosyltransferase (NAMPT) and cellular NAD+ content, which abolished 2-DG-induced potential radiosensitizing effect in glioma cells. Strikingly, NAD+ depletion evoked notable oxidative stress by NADPH reduction and hence re-radiosensitized 2-DG-treated glioma cells. Furthermore, isocitrate dehydrogenase-1 (IDH1) mutant U87 glioma cells with deficiency in the rate-limiting enzyme of Preiss-Handler pathway nicotinate phosphoribosyltransferase (Naprt1) revealed notable 2-DG-induced oxidative stress and radiosensitization. Our findings implied that targeting NAD+ could radiosensitize gliomas with GR, and 2-DG administration could be benefit for tumor patients with IDH1 mutation.

04 Sep 2018·Proceedings of the National Academy of SciencesQ1 · CROSS-FIELD

Personalized therapeutic delivery in the neurosurgical operating room

Q1 · CROSS-FIELD

Article

Author: Vogelbaum, Michael A.

Effective treatments for gliomas remain elusive despite decades of work investigating the biological basis of these tumors. There have been many recent advances in knowledge that have leveraged the tools of genetics, genomics, epigenetics, and proteomics to allow investigators to more finely subclassify and make more detailed prognostic assessments (1). However, many of the barriers that prevent the implementation of clinically effective therapeutics remain unbroken: intrinsic therapeutic resistance mechanisms, biological heterogeneity within and between the same type of tumor in different patients, and the presence of blood–brain and blood–tumor barriers that prevent most systemic therapeutics from reaching their tumor targets within the CNS at effective concentrations (2). More recently, there has been substantial interest in the development of therapeutics that do not require molecular access to the CNS, for example, antiangiogenic agents (3) and immunotherapeutics (4), which act on intravascular or systemic, non-CNS targets. These novel agents are being developed mostly for the treatment of higher grade gliomas, and glioblastoma (WHO grade IV glioma, GBM) in particular, and have yet to demonstrate survival benefit in randomized trials. For lower grade gliomas there have been few novel therapeutic options and treatment remains restricted to the conventional modalities of biopsy or surgical resection (to the extent feasible), radiation therapy, and cytotoxic chemotherapy. It is in the low-grade gliomas (WHO grade II, LGG) where an interesting molecular genetic discovery has been made: a tumor-initiating mutation in the IDH1 or IDH2 gene (5). These mutations result in a metabolic change within the Krebs cycle of tumor cells that renders the cells susceptible to depletion of NAD+ (6). While this finding is of considerable excitement to oncologists in general, neurooncologists have recognized that pharmacological depletion of NAD+ with use of systemically administered small-molecule inhibitors targeting nicotinamide phosphoribosyltransferase (NAMPT) is unlikely to produce meaningful … [↵][1]1Email: vogelbm{at}ccf.org. [1]: #xref-corresp-1-1

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