Syrosingopine | MCT4 inhibitor

Syrosingopine chemical structure

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Syrosingopine (84-36-6) is a reserpine derivative that is an inhibitor of monocarboxylate transporter 4 (IC50 MCT4 = 40 nM; IC50 MCT1 = 2.5 µM).1 It prevents lactate and H+ efflux. Syrosingopine elicits synthetic lethality in cancer cells in combination with metformin via NAD+ depletion leading to glycolytic blockade and cell death.1,2 It displays anticancer activity in several cancer models including leukemia3, breast4, NSCLC5, and glioblastoma6. Syrosingopine was originally used to treat hypertension via its antinoradrenergic effects.

References/Citations:

  1. Benjamin et al. (2018), Dual Inhibition of the Lactate Transporters MCT1 and MCT4 Is Synthetic Lethal with Metformin due to NAD+ Depletion in Cancer Cells; Cell Rep. 25 3047
  2. Benjamin et al. (2016), Syrosingopine sensitizes cancer cells to killing by metformin; Sci. Adv. 2 e1601756
  3. Saulle et al. (2021), Targeting Lactate Metabolism by Inhibiting MCT1 or MCT4 Impairs Leukemic Cell Proliferation, Induces Two Different Related Death-Pathways and Increases Chemotherapeutic Sensitivity of Acute Myeloid Leukemia Cells; Front. Oncol. 10 621458
  4. Buschhaus et al. (2023), Bone Marrow Mesenchymal Stem Cells Induce Metabolic Plasticity in Estrogen Receptor-Positive Breast Cancer; Mol. Cancer Res. 21 458
  5. Li et al. (2024), Syrosingopine and UK5099 synergistically suppress non-small cell lung cancer by activating the integrated stress response; Cell Death Dis. 15 431
  6. Behera et al. (2025), The Monocarboxylate Transporters MCT2 and MCT4 Are Highly Expressed in Glioblastoma and Crucially Implicated in the Pathobiology; Neuropathology 45 e70006
84-36-6, MCT4 inhibitor, monocarboxylate transporter inhibitor, Syrosingopine, Syrosingpine supplier

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Syrosingopine (84-36-6) is a reserpine derivative that is an inhibitor of monocarboxylate transporter 4 (IC50 MCT4 = 40 nM; IC50 MCT1 = 2.5 µM).1 It prevents lactate and H+ efflux. Syrosingopine elicits synthetic lethality in cancer cells in combination with metformin via NAD+ depletion leading to glycolytic blockade and cell death.1,2 It displays anticancer activity in several cancer models including leukemia3, breast4, NSCLC5, and glioblastoma6. Syrosingopine was originally used to treat hypertension via its antinoradrenergic effects.

References/Citations:

  1. Benjamin et al. (2018), Dual Inhibition of the Lactate Transporters MCT1 and MCT4 Is Synthetic Lethal with Metformin due to NAD+ Depletion in Cancer Cells; Cell Rep. 25 3047
  2. Benjamin et al. (2016), Syrosingopine sensitizes cancer cells to killing by metformin; Sci. Adv. 2 e1601756
  3. Saulle et al. (2021), Targeting Lactate Metabolism by Inhibiting MCT1 or MCT4 Impairs Leukemic Cell Proliferation, Induces Two Different Related Death-Pathways and Increases Chemotherapeutic Sensitivity of Acute Myeloid Leukemia Cells; Front. Oncol. 10 621458
  4. Buschhaus et al. (2023), Bone Marrow Mesenchymal Stem Cells Induce Metabolic Plasticity in Estrogen Receptor-Positive Breast Cancer; Mol. Cancer Res. 21 458
  5. Li et al. (2024), Syrosingopine and UK5099 synergistically suppress non-small cell lung cancer by activating the integrated stress response; Cell Death Dis. 15 431
  6. Behera et al. (2025), The Monocarboxylate Transporters MCT2 and MCT4 Are Highly Expressed in Glioblastoma and Crucially Implicated in the Pathobiology; Neuropathology 45 e70006