Ask about this productRelated genes to: MTHFD2 Blocking Peptide
- Gene:
- MTHFD2 NIH gene
- Name:
- methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 2, methenyltetrahydrofolate cyclohydrolase
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 2p13.1
- Locus Type:
- gene with protein product
- Date approved:
- 1999-07-23
- Date modifiied:
- 2015-09-04
Related products to: MTHFD2 Blocking Peptide
Related articles to: MTHFD2 Blocking Peptide
- - Source: PubMed
Publication date: 2026/05/07
Han JiusongWang WeiLi SiminWang Juan - BRAF V600 inhibitors are clinically approved for the treatment of BRAF-mutant melanoma in combination with a MEK inhibitor, but are ineffective in other melanoma subtypes. Moreover, pan-RAF inhibitors, such as belvarafenib, when combined with MEK inhibitors (cobimetinib), have promising but limited efficacy in non-BRAF-mutant melanomas. Here, we report that the mTOR inhibitor sapanisertib improves the efficacy of combined belvarafenib and cobimetinib therapy in NRAS, NF1, and KIT-mutant melanomas. Mechanistically, sapanisertib combined with belvarafenib and cobimetinib suppressed ATF4 expression and its target gene MTHFD2 while inducing DNA damage, revealing a previously underappreciated role of the ATF4-MTHFD2 axis in DNA damage repair and drug response. Human and murine models resistant to combined belvarafenib and cobimetinib exhibited elevated levels of ATF4 and MTHFD2 and were sensitive to sapanisertib. This study provides promising treatment opportunities for patients with non-BRAF-mutant melanomas, or those who relapse following belvarafenib and cobimetinib combination therapy. - Source: PubMed
Publication date: 2026/05/06
Cai FeiyangHuang FanGoncalves ChristopheSrikannan HarineeGagnon NataschaGuettler Elizabeth MMukeba-Harchies LéaMaxwell JenniferSu JieBijian KrikorJourne FabriceRose April A NOrthwein AlexandreDel Rincón Sonia VictoriaMiller Wilson H - MTHFD2, a critical enzyme in one-carbon metabolism, regulates cellular growth, redox balance, and energy homeostasis. Aberrant MTHFD2 expression has been implicated in the pathogenesis and progression of various diseases. MTHFD2 is a promising therapeutic target, however, its roles in diseases and upstream and downstream regulatory mechanisms have not been clarified. - Source: PubMed
Publication date: 2026/04/29
Wang XiangOu RenhaoXu YanaZheng GuowanXu HaifengLuo YingChen YunzhaoRen Xinxin - Chinese hamster ovary (CHO) cells are the dominant host for therapeutic protein production, yet intra- and inter-clonal heterogeneity in manufacturing phenotypes, and the underlying metabolic and secretory circuitry, remain poorly defined at single-cell resolution. Here, we apply secretion encoded single-cell sequencing (SEC-seq) to simultaneously measure transcriptomes and secreted IgG in single-cells from a parental production cell line and five CHO clones, each varying in cell-specific productivity. IgG mRNA and recombinant protein secretion are only moderately correlated across single cells, indicating that transcription alone does not explain intra-clonal secretion heterogeneity. By integrating SEC-seq with single-cell metabolic and secretory task scoring, we find that CHO cells accommodating recombinant protein expression burden have more active translation-associated pathways and suppressed energy-intensive endogenous secreted protein processing. Three high-secreting clones converge on this translation-focused state but differ in their subpopulation composition and energy/redox programs coupled to IgG output: one highly productive clone shows a low-growth, glycolytic, NAD/one-carbon-associated and UPR-activated program; a second shows increased oxidative phosphorylation and fatty-acid β-oxidation, and a third shows higher lipid-uptake with modest central carbon metabolism. Genes such as showed clone-specific correlations with IgG, linking glycolysis, mitochondrial respiration, fatty-acid metabolism, and redox to secretion. Together, these results demonstrate that SEC-seq can resolve IgG-coupled metabolic-secretory wiring within and between CHO clones, providing a framework to identify subpopulation and circuit features to engineer or select for improved recombinant protein production. - Source: PubMed
Publication date: 2026/04/17
Tat JasmineLay Fides DStevens JennitteLewis Nathan E - Mitochondria are critical for the malignant proliferation of tumor cells and their adaptation to harsh microenvironments. Using baicalein as the substrate, we designed and synthesized a series of novel mitochondrial-targeting baicalein phosphonium salt derivatives, and evaluated their in vitro antiproliferative activities against four tumor cell lines (A549, HCT116, SW620, CT26) and the normal HEK293 cell line. Compound 2c exhibited potent activity against the colon cancer cell line HCT116 with an IC₅₀ of 5.17 ± 0.48 μM and a selectivity index (SI) of ≈3.42, outperforming the positive control doxorubicin (DOX, SI ≈ 2.19). HPLC analysis confirmed the accumulation of 2c in tumor mitochondria, while in silico studies suggested its binding to MTHFD2, a mitochondrially localized protein upregulated in cancer cells. Cellular thermal shift assay (CETSA) and drug affinity responsive target stability (DARTS) verified that 2c directly binds to MTHFD2 intracellularly, and enzymatic assays demonstrated an IC₅₀ of 0.066 ± 0.014 μM against MTHFD2. Furthermore, 2c remarkably increased intracellular reactive oxygen species (ROS) levels, induced mitochondrial membrane potential depolarization, arrested the cell cycle at G0/G1 phase, and promoted apoptosis. In a mouse colon cancer graft model, compound 2c achieved a 49.70% tumor inhibition rate at a dose of 20 mg/kg, with no obvious abnormalities observed in major organs. In conclusion, 2c is an effective mitochondrial MTHFD2 inhibitor with potential to develop into a potent anti-colon cancer drug. - Source: PubMed
Publication date: 2026/04/02
Hong AotianLi LeiSong MingjieHan JiahongCai EnboGuan Lili