pkm2-in-1

PKM2-IN-1 (compound 3k) exhibits inhibitory activity against PKM2 with an IC50 of 2.95 μM, while the IC50 for PKM1 is 4-5 times higher.

PKM2-IN-10 is a PKM2 inhibitor. It effectively suppresses the proliferation of A549 and HCC1833 cell lines with IC50 values of 3.36 μM and 9.20 μM, respectively. PKM2-IN-10 demonstrates antitumor activity in human non-small cell lung cancer (NSCLC) and mouse lung adenocarcinoma models. It is applicable for research in lung cancer.

PKM2-IN-11 is a PKM2 inhibitor with an IC50 value of 0.363 μM. It operates through dual mechanisms, inhibiting pyruvate kinase M2 (PKM2) and stabilizing microtubules. This compound reduces PKM2 protein levels in MCF-7 cells, slightly decreases reactive oxygen species (ROS) levels, and significantly increases early apoptosis in cells. Additionally, PKM2-IN-11 induces G2/M phase arrest and is applicable in breast cancer research.

PKM2-IN-12 is an orally active PKM2 inhibitor with an IC50 of 10 nM. It effectively hinders the proliferation and migration of COLO-205 cells, induces cell cycle arrest, and triggers apoptosis (apoptosis). PKM2-IN-12 significantly reduces lactate, pyruvate, and ROS levels in cells. In mouse models, it not only directly targets cancer cells but also restores disrupted intestinal microecological balance. PKM2-IN-12 is useful for colorectal cancer research.

PKM2-IN-13 is a selective inhibitor of PKM2 with an IC50 value of 55.13 μM. This compound demonstrates broad-spectrum anticancer activity while exhibiting low toxicity to normal cells. PKM2-IN-13 induces apoptosis by elevating reactive oxygen species (ROS) levels and activating Caspase-3/7. It interacts with pyruvate kinase M2 in vitro, inhibiting its glycolytic function. Additionally, PKM2-IN-13 has shown a good safety profile, with no significant adverse effects observed in in vivo experiments. It can be utilized in research studies involving oral squamous cell carcinoma, colon cancer, breast cancer, and melanoma.

Mitapivat (PKR-IN-1), also known as PKM2 activator 1020 is a PKM2 activator (pyruvate kinase activator) for the treatment of pyruvate kinase deficiency.

PKM2 modulator 1 (compound C998) is an effective PKM2 inhibitor with antiproliferative activity. It induces apoptosis and holds potential for research in glioblastoma studies.

PKM2 Activator 4, a chemical compound, functions as an activator of PKM2 with an activation concentration (AC 50) ranging from 1 to 10 μM. It is primarily utilized in cancer research.

PKM2/PDK1-IN-1, a shikonin thioether derivative, serves as a dual inhibitor for PKM2/PDK1. This compound effectively inhibits the proliferation and induces apoptosis in NSCLC cells. It promotes intercellular ROS production and modulates apoptotic proteins, engaging in both mitochondrial and death receptor pathways [1].

Vitamin K5 (Synkamin), a photosensitizer and antimicrobial agent, serves as a specific PKM2 inhibitor, demonstrating IC 50 values of 28, 191, and 120 μM against PKM2, PKM1, and PKL, respectively. It induces apoptosis in colon 26 cells and is utilized in infection and cancer research. Additionally, Vitamin K5 finds application as a preservative in pharmaceuticals, foods, and beverages [1] [2] [3].

MTP, a PKM2 inhibitor, promotes apoptosis in cancer cells via caspase-3 activation while also inducing autophagy and enhancing ROS generation. Further, it inhibits JAK2 signaling, rendering it useful for the study of oral squamous cell carcinoma [1].

Compound 5C, referred to as Pkm2-in-4, is a selective PKM2 inhibitor (IC50 = 0.35 µM) that modulates pyruvate-dependent respiration and promotes mitochondrial H2O2 production rate and electron transport system coupling [1].

Compound Z10 (PKM2 activator 6) serves as both a PKM2 activator and a PDK1 inhibitor, exhibiting dissociation constants (K D ) of 121 μM and 19.6 μM, respectively. It promotes apoptosis in colorectal cells while suppressing their proliferation and migration, additionally inhibiting glycolysis. Compound Z10 demonstrates inhibitory effects on the proliferation of various cell lines, including DLD-1, HCT-8, HT-29, and MCF-10A, with half-maximal inhibitory concentrations (IC 50 ) of 10.04 μM, 2.16 μM, 3.57 μM, and 66.39 μM, as recorded in reference [1].

NPD10084 is an inhibitor that targets the pyruvate kinase M2 subtype (PKM2). NPD10084 inhibits downstream signaling by interfering with protein-protein interactions between PKM2 and β-catenin or STAT3 through its action on the non-glucolytic signaling function of PKM2, thereby exhibiting antiproliferative activity against multiple colorectal cancer cell lines (in vitro IC₅₀ range: 0.8–1.9 μM).

PKM2-IN-6 (compound 7d) is an orally active PKM2 inhibitor (IC50=23 nM) capable of inducing apoptosis and G2 cell cycle arrest. It reduces PKM1 and PKM2 expression at the mRNA level, exhibits antitumour activity, and is suitable for investigating triple-negative breast cancer (TNBC).

Vitamin K5 hydrochloride is a photosensitizer and antimicrobial agent that functions as a specific inhibitor of pyruvate kinase M2 (PKM2), with IC50 values of 28 μM for PKM2, 191 μM for PKM1, and 120 μM for PKL. Vitamin K5 hydrochloride induces apoptosis in colon 26 cells, supporting its application in infection and cancer research as well as its practical use as a preservative in pharmaceutical, food, and beverage formulations.