PKM2 inhibitor

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 inhibitor G is a inhibitor of pyruvate kinase.

FX-11 (LDHA Inhibitor FX11) is A potent, selective and competitive specific inhibitor of lactate dehydrogenase A (LDHA) with a Ki of 8 μM. FX-11 can activate PKM2 (pyruvate kinase M2). FX-11 can reduce ATP levels, induce oxidative stress and ROS production, and cause cell death. FX-11 appeared antitumor activity during xenotransplantation of lymphoma and pancreatic cancer.

Cytarabine (Ara-C) is a nucleoside analog, an inhibitor of DNA synthesis (IC50=16 nM). Cytarabine inhibits DNA polymerase and induces cell cycle arrest, autophagy, and apoptosis. Cytarabine has antitumor activity.

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

Shikonin (Anchusa acid) is a natural product, a TMEM16A chloride channel inhibitor (IC50=6.5 μM) and selective PKM2 inhibitor. Shikonin exhibits antitumor, anti-inflammatory and wound healing activities.

Cynaroside (Luteolin 7-O-Glucoside) is a flavone, a flavonoid-like chemical compound. It has an anti-oxidant effect, inhibiting lipid and protein oxidation.

DASA-58 is a specific and potent Pyruvate kinase M2 (PKM2) activator.

TEPP-46 (ML265) is an activator of pyruvate kinase M2 (PKM2) (AC50=92 nM), selective for PKM1, PKL and PKR. TEPP-46 has antitumor activity.

D34-919 is a potent inhibitor of the ALDH1A3-PKM2 interaction, effectively inhibiting the ALDH1A3-mediated tetramerization enhancement of PKM2. Treatment mediated by D34-919 both in vitro and in vivo enhances and restores apoptosis and sensitivity in glioblastoma (GBM) cells induced by radiochemotherapy.

PKM2-IN-8 (Compound 9b) is an inhibitor of pyruvate kinase M2 (PKM2) with an IC50 of 0.31 μM. It exhibits potent antiproliferative activity against U87MG glioma cells. PKM2-IN-8 induces early apoptosis and reduces lactate levels. This compound is useful for research in glioblastoma.

PKM2-IN-9 (compound C1) is a potent inhibitor of PKM2, demonstrating a 75% inhibition rate at 50 μM. It plays a significant role in cancer research.

PKM2 modulator 2 (compound C599) is a potent inhibitor of PKM2, displaying antiproliferative activity and inducing apoptosis. This compound holds potential for research in glioblastoma.

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-IN-3 is a potent PKM2 kinase inhibitor, displaying an IC 50 value of 4.1 μM. The compound effectively suppresses PKM2-mediated glycolysis and NLRP3 activation, thereby exerting an anti-neuroinflammatory effect.

Alkannin is a potent and specific inhibitor of tumor-specific pyruvate kinase-M2 (PKM2) without affecting PKM1 or pyruvate kinase-L (PKL), making it a potential anticancer agent [1].

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].

CIAC001, a pyruvate kinase PKM2 inhibitor, exhibits anti-neuroinflammatory properties. It effectively suppresses LPS-induced production of proinflammatory nitric oxide (NO) and provides protection to immunologically active BV-2 cells with an IC50 value of 2.5 μM. Additionally, CIAC001 demonstrates anti-neuroinflammation effects in mouse models and attenuates chronic morphine-induced addiction [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 of pyruvate kinase PKM2 that blocks non-glycolytic signaling in cancer cells by disrupting PKM2's interaction with β-catenin or STAT3, thus inhibiting downstream pathways. It demonstrates antiproliferative effects against colorectal cancer cells both in vitro and in vivo [1].

PKM2-IN-6 (compound 7d) is a potent PKM2 inhibitor that can be administered orally and demonstrates an IC 50 value of 23 nM. It triggers apoptosis and causes cell cycle arrest in the G2 phase, while also reducing the mRNA levels of both PKM1 and PKM2. Additionally, PKM2-IN-6 exhibits anticancer properties and shows promise for research in triple-negative breast cancer [1].