LW6 | Malate dehydrogenase inhibitor

LW6 chemical structure

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LW6 (934593-90-5) is an inhibitor of malate dehydrogenase (MDH) (IC50’s: MDH1 = 1.1 µM; MDH2 = 6.3 µM).1,2  It inhibits Hypoxia-Inducible Factor-1 (HIF-1) by a variety of reported mechanisms.3-5 LW6 displayed antitumor properties in hepatocellular6 and pancreatic cancer7 cell lines. It promoted rat locomotor function after spinal cord injury via reduction of neuroinflammation.8

References/Citations:

  1. Lee et al. (2013), Identification of Malate Dehydrogenase 2 as a Target Protein of the HIF-1 Inhibitor LW6 using chemical probes; Ang. Chem. Int. Ed. Eng. 52 10286
  2. Naik et al. (2017), Methyl 3-(3-(4-(2,4,4-trimethylpentan-2-yl)phenoxy)propanamido)benzoate as a Novel and Dual Malate Dehydrogenase (MDH) 1/2 Inhibitor Targeting Cancer Metabolism; J. Med. Chem. 60 8631
  3. Lee et al. (2010), LW6, a novel HIF-1 inhibitor, promotes proteasomal degradation of HIF-1alpha via upregulation of VHL in a colon cancer cell line; Biochem. Pharmacol. 80 982
  4. Sato et al. (2015), LW6, a hypoxia-inducible factor 1 inhibitor, selectively induces apoptosis in hypoxic cells through depolarization of mitochondria in A549 human lung cancer cells; Mol. Med. Rep. 80 982
  5. Ban et al. (2016), A Novel Malate Dehydrogenase 2 Inhibitor Suppresses Hypoxia-Inducible Factor-1 by Regulating Mitochondrial Respiration; PLoS One 11 e0162568
  6. Xu et al. (2022), The hypoxia-inducible factor 1 inhibitor LW6 mediates the HIF-1alpha/PD-L1 axis and suppresses tumor growth of hepatocellular carcinoma in vitro and in vivo; Eur. J. Pharmacol. 930 175154
  7. Zhane et al. (2019), LW6 enhances chemosensitivity to gemcitabine and inhibits autophagic flux in pancreatic cancer; J. Adv. Res. 20 9
  8. Li et al. (2025), Hypoxia-Inducible Factor-1α-Induced Astrocytic D-Dopachrome Tautomerase Activates Microglial Inflammatory Response following Spinal Cord Injury; Am. J. Pathol. 195 1676
934593-90-5, HIF-1 inhibitor, LW6, LW6 supplier, malate dehydrogenase inhibitor

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LW6 (934593-90-5) is an inhibitor of malate dehydrogenase (MDH) (IC50’s: MDH1 = 1.1 µM; MDH2 = 6.3 µM).1,2  It inhibits Hypoxia-Inducible Factor-1 (HIF-1) by a variety of reported mechanisms.3-5 LW6 displayed antitumor properties in hepatocellular6 and pancreatic cancer7 cell lines. It promoted rat locomotor function after spinal cord injury via reduction of neuroinflammation.8

References/Citations:

  1. Lee et al. (2013), Identification of Malate Dehydrogenase 2 as a Target Protein of the HIF-1 Inhibitor LW6 using chemical probes; Ang. Chem. Int. Ed. Eng. 52 10286
  2. Naik et al. (2017), Methyl 3-(3-(4-(2,4,4-trimethylpentan-2-yl)phenoxy)propanamido)benzoate as a Novel and Dual Malate Dehydrogenase (MDH) 1/2 Inhibitor Targeting Cancer Metabolism; J. Med. Chem. 60 8631
  3. Lee et al. (2010), LW6, a novel HIF-1 inhibitor, promotes proteasomal degradation of HIF-1alpha via upregulation of VHL in a colon cancer cell line; Biochem. Pharmacol. 80 982
  4. Sato et al. (2015), LW6, a hypoxia-inducible factor 1 inhibitor, selectively induces apoptosis in hypoxic cells through depolarization of mitochondria in A549 human lung cancer cells; Mol. Med. Rep. 80 982
  5. Ban et al. (2016), A Novel Malate Dehydrogenase 2 Inhibitor Suppresses Hypoxia-Inducible Factor-1 by Regulating Mitochondrial Respiration; PLoS One 11 e0162568
  6. Xu et al. (2022), The hypoxia-inducible factor 1 inhibitor LW6 mediates the HIF-1alpha/PD-L1 axis and suppresses tumor growth of hepatocellular carcinoma in vitro and in vivo; Eur. J. Pharmacol. 930 175154
  7. Zhane et al. (2019), LW6 enhances chemosensitivity to gemcitabine and inhibits autophagic flux in pancreatic cancer; J. Adv. Res. 20 9
  8. Li et al. (2025), Hypoxia-Inducible Factor-1α-Induced Astrocytic D-Dopachrome Tautomerase Activates Microglial Inflammatory Response following Spinal Cord Injury; Am. J. Pathol. 195 1676