Pyruvate Kinase Inhibitor

GCN2 activator-1 (Compound 20) is a GCN2 activator. GCN2 activator-1 binds within the ATP-pocket of GCN2 and activates GCN2 in a GCN1-independent manner. GCN2 activator-1 activates Integrated Stress Response (ISR) in cells. GCN2 activator-1 inhibits PKR with an IC₅₀ of 3.75 µM. GCN2 activator-1 can be used for research of pulmonary veno-occlusive disease (PVOD).

Thujopsene is the inhibitor for cytochrome P450, that inhibits CYP2B6, CYP3A4, CYP2C19, CYP2C8, CYP2C9 with IC₅₀s of 1.3, 12.6, 13.6, 29.8, and 44.9 μM, respectively. Thujopsene binds to PKM2, inhibits the metabolism pathway of cancer cell, induces apoptosis in MKN45, thereby exhibiting antitumor efficacy. Thujopsene exhibits anti-termite and antifungal activities through autoxidation.

3-Carene is an orally active TCA cycle enzyme inhibitor. 3-Carene inhibits succinate dehydrogenase and malate dehydrogenase as well as pyruvate kinase, disrupting energy metabolism. 3-Carene disrupts cell wall and cell membrane integrity, leading to potassium ion leakage, protein leakage, membrane depolarization, ATP depletion, morphological disruption, and cell lysis. 3-Carene interferes with amino acid metabolism, pantothenate and CoA biosynthesis, purine and pyrimidine metabolism, and aminoacyl-tRNA biosynthesis. 3-Carene enhances GABA receptor-mediated synaptic responses. 3-Carene can be used in research on bacterial infections, inflammation, anxiety, and sleep disorders.

Deoxytopsentin (compound 5) is a marine bisindole alkaloid and also a MRSA pyruvate kinase inhibitor. Deoxytopsentin exists in sponges. Deoxytopsentin exhibits antibacterial activity against methicillin-resistant Staphylococcus aureus strains in vitro.

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.

LIQ1, a flavonoid derivative, is a potent Pyruvate kinase M2 (PKM2) allosteric inhibitor (IC₅₀ = 0.39 μM; K_d = 4.5 μM) targeting Arg43 within the polyarginine pocket. LIQ1 exhibits efficacy in a mouse model of LPS (HY-D1056)-induced endotoxemia, preventing the nuclear translocation of PKM2 and inhibiting its binding to HIF-1α, thereby suppressing IL-1β transcription. LIQ1 can be used for the research of endotoxemia^[1].

PARP1/PKM2-IN-1 is a dual PARP1/PKM2 inhibitor, with an IC₅₀ of 39.5 nM against PARP1, and IC₅₀ values of 261 nM (recombinant PKM2) and 50 nM (dimeric PKM2) against PKM2. PARP1/PKM2-IN-1 reduces the dimerization of PKM2 and decreases its nuclear accumulation level. PARP1/PKM2-IN-1 also selectively downregulates PKM2 mRNA and impairs poly (ADP-ribose)-mediated nuclear retention of PKM2. PARP1/PKM2-IN-1 exhibits antiproliferative activity and inhibits the formation of 3D cancer spheroids. PARP1/PKM2-IN-1 can be used in research related to mammary adenocarcinoma, triple-negative breast cancer, BRCA1-mutant triple-negative breast cancer, and prostate adenocarcinoma.

PKM2-IN-10 (Compound 16) is a PKM2 inhibitor. PKM2-IN-10 inhibits the proliferation of A549 and HCC1833 cell lines with IC₅₀ of 3.36 μM and 9.20 μM, respectively. PKM2-IN-10 exhibits antitumor activity in human non-small cell lung cancer (NSCLC) and mouse lung adenocarcinoma models. PKM2-IN-10 can be used in lung cancer research.

PKM2 modulator 2 (compound C599) is a potent PKM2 inhibitor. PKM2 modulator 2 shows antiproliferative activity. PKM2 modulator 2 induces apoptosis. PKM2 modulator 2 has the potential for the research of glioblastoma.

PKM2-IN-13 is a selective PKM2 inhibitor inhibiting PKM2 with an IC₅₀ value of 55.13 μM. PKM2-IN-13 exhibits broad-spectrum anticancer activity with low toxicity to normal cells. PKM2-IN-13 induces apoptosis by elevated ROS levels and activation of caspases 3/7, and interacts with and inhibits the glycolytic activity of Pyruvate Kinase M2 in virto. PKM2-IN-13 demonstrates a favorable safety profile with no significant adverse effects in vivo. PKM2-IN-13 can be used for oral squamous cell carcinoma (OSCC), colon carcinoma, breast cancer and melanoma research.

PKM2-IN-12 is an orally active PKM2 inhibitor with an IC₅₀ of 10 nM. PKM2-IN-12 inhibits COLO-205 cell proliferation and migration, arrests the cell cycle, and induces apoptosis. PKM2-IN-12 significantly reduces cellular levels of lactate, pyruvate, and ROS. PKM2-IN-12 directly kills cancer cells and restores disrupted gut microbiota balance in mice model. PKM2-IN-12 can be used to study colorectal cancer.

PKM2-IN-8 (Compound 9b) is a pyruvate kinase M2 (PKM2) inhibitor (IC₅₀ = 0.31 μM). PKM2-IN-8 has potent antiproliferative activity against U87MG glioma cells. PKM2-IN-8 can induce early apoptosis and reduce lactate levels. PKM2-IN-8 can be used for the research of glioblastoma.

Iminostilbene (Standard) is the analytical standard of Iminostilbene. This product is intended for research and analytical applications. Iminostilbene is a a chemical precursor of carbamazepine.

SET-171 is a JNK (c-Jun N-terminal kinase) inhibitor that exhibits significant anticancer activity and lipid metabolism regulation by inhibiting liver pyruvate kinase (PKL) expression. In anticancer studies, SET-171 shows IC₅₀ values of 8.82 μM and 2.97 μM against HepG2 and Huh7 cell lines, respectively, indicating high cytotoxicity. Additionally, in non-alcoholic fatty liver disease (NAFLD)-related studies, SET-171 significantly reduces triacylglycerol (TAG) levels and inhibits the expression of steatosis-related proteins. SET-171 holds promise for research on hepatocellular carcinoma (HCC) and NAFLD.

Antifungal agent 175 is a potent antifungal agent with an EC₅₀ of 1.8 μg/mL against R. solani. Antifungal agent 175 Z17 exerts its effects primarily by disrupting the cell membranes of pathogenic fungi to trigger lipid peroxidation and oxidative stress, inhibiting pyruvate kinase (PK) to interfere with energy metabolism, and binding to the cytochrome bc1 complex. Antifungal agent 175 can be used in research on rice sheath blight.

PKM2-IN-11 is a PKM2 inhibitor (IC₅₀ = 0.363 μM). PKM2-IN-11 has dual mechanisms involving pyruvate kinase M2 (PKM2) inhibition and microtubule stabilization. PKM2-IN-11 can decrease PKM2 protein levels in MCF-7 cells. PKM2-IN-11 can slightly reduce reactive oxygen species (ROS) levels and significantly increase early apoptotic cells. PKM2-IN-11 induces G2/M phase arrest. PKM2-IN-11 can be used for the study of breast cancer.

PKCζ/ι pseudosubstrate inhibitor has broad-spectrum effects on the PKC enzyme family and can induce memory impairment.

Vitamin K5 (Synkamin) is a photosensitizer and a antimicrobial agent. Vitamin K5 is a specific PKM2 inhibitor with IC₅₀ values of 28, 191 and 120 μM for PKM2, PKM1 and PKL. Vitamin K5 induces apoptosis of colon 26 cells. Vitamin K5 can be used for the research of infection and cancer, and it also can be used as a preservative for pharmaceuticals, foods, and beverages.

Multi-target kinase-IN-9 is a multi-target enzyme inhibitor with antiproliferative and antiangiogenic activities, and exhibits remarkable selectivity against hepatocellular carcinoma cells. By broadly binding to the active sites or ATP-binding regions of multiple key enzymes including DNA polymerase β, Pyruvate Kinase M2 (PKM2), Multi-target kinase-IN-9 comprehensively disrupts DNA repair and replication, glycolysis, chromatin dynamics and transcriptional programs, and blocks the self-renewal of cancer stem cells. Multi-target kinase-IN-9 induces genomic instability, lysosomal dysfunction and autophagic flux impairment, thereby triggering tumor cell death, effectively inhibiting tumor proliferation, invasion, metastasis and angiogenesis, and significantly reducing tumor volume in xenograft models. Multi-target kinase-IN-9 is applicable to hepatocellular carcinoma-related research.

Pkm2-in-4 (compound 5C) is a selective inhibitor of PKM2 (IC₅₀=0.35 μM), which regulates pyruvate-dependent respiration and induces mitochondrial H202 production rate and electron transport system coupling.