METTL1-WDR4-IN-1 TFA 

METTL1-WDR4-IN-1 (Compound 1) TFA is a selective competitive inhibitor of the methyltransferase complex METTL1-WDR4 (IC₅₀=144 μM). METTL1-WDR4-IN-1 TFA inhibits the m⁷G methyltransferase activity of the METTL1-WDR4 complex, blocking the m⁷G modification of PKM mRNA, reducing PKM2 protein expression, disrupting the METTL1/PKM2/H3K9la positive feedback loop, and simultaneously inhibiting PKM2 nuclear translocation-mediated CD155 transcriptional activation. METTL1-WDR4-IN-1 TFA can inhibit tumor cell proliferation, weaken glycolytic metabolism, reverse tumor immune evasion (restoring NK cell and CD8⁺ T cell function), and regulate RNA epigenetic modification and the tumor immune microenvironment. METTL1-WDR4-IN-1 TFA can be used in immunotherapy research for cancers such as colorectal cancer, and is particularly suitable for use in combination with PKM2 inhibitors to enhance anti-tumor treatment efficacy^[1][2].

METTL1-WDR4-IN-1 TFA, as a METTL1 inhibitor, downregulates METTL1 protein and mRNA expression in HCT-116 and RKO CRC cells, inhibits m7G modification of PKM mRNA, and reduces PKM2 protein levels^[2].
METTL1-WDR4-IN-1 TFA inhibits glycolysis in CRC cells, reducing extracellular acidification rate (ECAR) and lactate accumulation, and downregulating H3K9la histone modification levels^[2].
METTL1-WDR4-IN-1 TFA inhibits PKM2 nuclear translocation in CRC cells, reduces CD155 transcription and protein expression, and enhances the expression of NK cell activation-related markers CD107a and CD16^[2].
METTL1-WDR4-IN-1 TFA, in combination with the PKM2 inhibitor Shikonin, synergistically downregulates PKM2, H3K9la, and CD155 expression in CRC cells and synergistically inhibits cell proliferation^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

355.29

C₁₀H₁₂F₃N₅O₄S

Solid

Light yellow to orange

OC(C(F)(F)F)=O.S=C1N=C2C(N1)=C(N)N=CN2CC(CO)O

Room temperature in continental US; may vary elsewhere.

4°C, sealed storage, away from moisture and light

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light)

• [1]. Francesco Nai, et al. Small-Molecule Inhibitors of the m7G-RNA Writer METTL1. ACS Bio Med Chem Au 2023, Publication Date:December 12, 2023