syrosingopine / Generic mfg. - LARVOL DELTA

PRL-3 enhances multiple myeloma cell survival in acidic microenvironments via metabolic adaptation and pH regulation. (ASH 2025) - "Pharmacologic inhibition of lactate and proton transport was performed using Syrosingopine (dualMCT inhibitor), AZD0095 (MCT4 inhibitor), AZD3965 (MCT1 inhibitor), Bafilomycin A1 (v-ATPase inhibitor),and ethyl isopropyl amiloride (EIPA; NHE1 inhibitor). Thissuggests compensatory roles among transporters and pathways whose importance varies depending onthe pH level. Increased metabolism and proton transport are associated with high PRL-3 expression,supporting PRL-3 as a key protein for cell survival in acidic conditions and a potential therapeutic targetin myeloma treatment."

Hematological Malignancies • Multiple Myeloma • ANXA5 • PTP4A3 • SLC16A1

Drug targeting of the monocarboxylate transporter MCT4 is a novel treatment strategy for metastatic ccRCC. (PubMed, Pharmacol Res) - "Alone or combined with inhibition of mitochondrial respiration by metformin and phenformin, the MCT4 inhibitor syrosingopine significantly inhibits lactate efflux, induces cell viability reduction in four different RCC cell lines and patient-derived 2D/3D models, and alterations in cellular metabolism and mitochondrial respiration. Six patient-derived RCC air-liquid interface models, mimicking the complex RCC architecture, corroborate these data. Beyond potential prediction of patient outcome using MCT4 expression and DNA methylation at specific CpG sites, drug targeting of MCT4 and inhibiting mitochondrial respiration synergistically is a novel treatment strategy for metastatic ccRCC."

Journal • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • SLC16A3

N-acetylcysteine induced lactate reprogramming is a targetable metabolic susceptibility in glioblastoma. (SNO 2025) - "To test the effects of lowering lactate levels on NAC-induced cytotoxicity, we treated glioma cells with the mitochondrial pyruvate dehydrogenase enzyme complex inhibitor dichloroacetate (DCA)...Blocking lactate import/export via inhibition of MCT transporters (AZD3965 and Syrosingopine) significantly enhances NAC-induced cytotoxicity...Our data suggests that lactate reprogramming is a targetable susceptibility of NAC treatment. The unique sensitivity of GBM towards NAC and its dependence on lactate as an oncometabolite governing metabolic resistance might open a novel druggable pathway for treating both IDHwt and IDHmut gliomas."

Brain Cancer • Glioblastoma • Glioma • Solid Tumor • LDHA

N-acetylcysteine induced lactate reprogramming is a targetable metabolic susceptibility in glioblastoma. (SNO 2025) - "To test the effects of lowering lactate levels on NAC-induced cytotoxicity, we treated glioma cells with the mitochondrial pyruvate dehydrogenase enzyme complex inhibitor dichloroacetate (DCA)...Blocking lactate import/export via inhibition of MCT transporters (AZD3965 and Syrosingopine) significantly enhances NAC-induced cytotoxicity...Our data suggests that lactate reprogramming is a targetable susceptibility of NAC treatment. The unique sensitivity of GBM towards NAC and its dependence on lactate as an oncometabolite governing metabolic resistance might open a novel druggable pathway for treating both IDHwt and IDHmut gliomas."

Brain Cancer • Glioblastoma • Glioma • Solid Tumor • LDHA

N-acetylcysteine induced lactate reprogramming is a targetable metabolic susceptibility in glioblastoma. (WFNOS 2025) - "To test the effects of lowering lactate levels on NAC-induced cytotoxicity, we treated glioma cells with the mitochondrial pyruvate dehydrogenase enzyme complex inhibitor dichloroacetate (DCA)...Blocking lactate import/export via inhibition of MCT transporters (AZD3965 and Syrosingopine) significantly enhances NAC-induced cytotoxicity...Our data suggests that lactate reprogramming is a targetable susceptibility of NAC treatment. The unique sensitivity of GBM towards NAC and its dependence on lactate as an oncometabolite governing metabolic resistance might open a novel druggable pathway for treating both IDHwt and IDHmut gliomas."

Brain Cancer • Glioblastoma • Glioma • Oncology • Solid Tumor • LDHA

N-acetylcysteine induced lactate reprogramming is a targetable metabolic susceptibility in glioblastoma. (WFNOS 2025) - "To test the effects of lowering lactate levels on NAC-induced cytotoxicity, we treated glioma cells with the mitochondrial pyruvate dehydrogenase enzyme complex inhibitor dichloroacetate (DCA)...Blocking lactate import/export via inhibition of MCT transporters (AZD3965 and Syrosingopine) significantly enhances NAC-induced cytotoxicity...Our data suggests that lactate reprogramming is a targetable susceptibility of NAC treatment. The unique sensitivity of GBM towards NAC and its dependence on lactate as an oncometabolite governing metabolic resistance might open a novel druggable pathway for treating both IDHwt and IDHmut gliomas."

Brain Cancer • Glioblastoma • Glioma • Solid Tumor • LDHA

Lactate Monocarboxylate Transporter (MCT1/4) Inhibitor Syrosingopine Restores Adaptive Repair in Kidney Injury (KIDNEY WEEK 2025) - "Sc-RNA seq analysis showed profound cell-specific metabolic changes in SYR-treated kidneys compared to controls, coupled with significant suppression of macrophage clusters. Conclusion The MCT1/4 inhibitor syrosingopine reduces AKI to CKD transition by ameliorating fibrosis, inflammation and metabolic dysregulation—highlighting its potential as a novel therapeutic strategy against AKI."

Acute Kidney Injury • Cardiovascular • Chronic Kidney Disease • Fibrosis • Immunology • Inflammation • Metabolic Disorders • Nephrology • Renal Disease • Reperfusion Injury • ICAM1 • IFNG • TGFB1 • VCAM1

Targeting Metabolic Signatures of Tumor-Associated Macrophages in High-Grade Brain Tumor (AMP 2025) - "In orthotopic GBM mouse models, an MCT1/4 inhibitor (syrosingopine) was tested alone or with anti-PD-1, and tumor growth, survival, and immune cell infiltration were monitored... TAM-derived lactate is a critical driver of GBM DNA repair and immune escape through KU70 lactylation-mediated NHEJ enhancement. Inhibiting lactate transport disrupts this mechanism, leading to unrepaired DNA accumulation and innate immune activation. These findings underscore a novel link between tumor metabolism and DNA repair, and support combining lactate blockade with immune checkpoint inhibitors as a promising strategy in glioblastoma."

IO biomarker • Brain Cancer • Glioblastoma • Glioma • Oncology • Solid Tumor • CD8 • STING

Alpha-enolase influences ATP pool of cytoplasm and lactate homeostasis by regulating glycolysis in gastric cancer. (PubMed, Signal Transduct Target Ther) - "Furthermore, pharmacological studies revealed that metformin combined with copanlisib significantly inhibited tumors by blocking the energy metabolism pathways PI3K/AKT and AMPK/mTOR. Rationally, targeting multiple nodes along the ENO1-ATP/lactate-AMPK/PI3K/AKT-mTOR axis may be effective for GC treatment, as indicated by the significant suppression of tumor growth by metformin (which inhibits ATP production) plus syrosingopine (which disrupts lactate homeostasis). In conclusion, the complex interplay between metabolism and tumor stemness offers novel therapeutic directions and potential treatment strategies for GC."

Biomarker • Journal • Gastric Cancer • Oncology • Solid Tumor • ENO1

Molecularly Engineered Nanoagents with Efficient Free Radicals Generation and Photothermal Conversion Performance for Enhanced Tumor Photoimmunotherapy via Targeting Lactate Metabolism-Immune Circuit Rewiring. (PubMed, Adv Mater) - "Herein, a lactate metabolism checkpoint blockade strategy targeting monocarboxylate transporter 4 (MCT4) is proposed to augment photoimmunotherapy by co-delivering MCT4 inhibitor syrosingopine (SY) and a phototheranostic agent L8BO (L8)...Concurrently, natural killer (NK) cell activation and memory T-cell differentiation are achieved, thereby suppressing both localized and distal tumor progression whilst concomitantly curtailing pulmonary metastatic dissemination. In brief, this study provides a novel combinatorial paradigm to potentiate photoimmunotherapy by targeting the lactate metabolism-immune circuit rewiring strategy."

Journal • Oncology

Mitochondrial fission factor drives an actionable metabolic vulnerability in multiple myeloma. (PubMed, Haematologica) - "Finally, we highlight a novel lactate-MFF axis involved in proteasome inhibitor resistance, and show that combining AZD3965 or Syrosingopine with bortezomib results in synergistic anti-MM activity along with MFF down-regulation. Collectively, these data point to MFF-dependent mitochondrial fragmentation as a key metabolic hallmark of MM, providing a framework for the development of novel therapeutic strategies targeting mitochondrial dynamics and harnessing the metabolic plasticity of malignant plasma cells."

Journal • Hematological Malignancies • Multiple Myeloma • Oncology

The Monocarboxylate Transporters MCT1 and MCT4 Are Highly Expressed in Glioblastoma and Crucially Implicated in the Pathobiology. (PubMed, Neuropathology) - "The results indicated the role of MCT1/4 in the pathobiology of GBM and the diagnostic utility at the immunohistochemical level. Syrosingopine, an antihypertensive agent with good CNS penetration and previously used in different malignancies, may be an essential therapeutic adjunct in GBM."

Journal • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Metabolic Disorders • Oligodendroglioma • Oncology • Solid Tumor • SLC16A1

Repurposing brucine as a chemopreventive agent in mammary gland carcinoma: Regulating lactate transport through MCT-4. (PubMed, Toxicol Rep) - "Syrosingopine (SRY) is a well-established inhibitor of lactate transport through MCT-4...BRU demonstrated significant cytotoxicity and increased the extracellular lactate levels in MCF-7 cells. The findings strongly encouraged BRU's effectiveness, offering promising paths for subsequent investigations."

Journal • Breast Cancer • Cardiovascular • Hypertension • Oncology • Solid Tumor

Post-ischemic inactivation of HIF Prolyl Hydroxylases in endothelium promotes maladaptive kidney repair by inducing glycolysis. (PubMed, J Clin Invest) - "Strikingly, treatment with the MCT4 inhibitor syrosingopine restored adaptive kidney repair in PHDTiEC mice. Mechanistically, MCT4 inhibition suppressed pro-inflammatory EC activation reducing monocyte-endothelial cell interaction. Our findings suggest avenues for halting AKI to CKD transition based on selectively targeting the endothelial hypoxia-driven glycolysis/MCT4 axis."

Journal • Acute Kidney Injury • Chronic Kidney Disease • Fibrosis • Immunology • Inflammation • Nephrology • Renal Disease • SLC16A3

HLA is a potent immunoinflammatory target in asymptomatic Alzheimer's disease. (PubMed, Neuroscience) - "Five FDA-approved drugs (Itrazole, Dfo, Syrosingopine, Cefoperazone and Pradaxa) were predicted as the common drug-targeted HLA-C and HLA-DRB1 by molecular docking. Taken together, the changes in the immune microenvironment of asymptomatic AD, and provided a new perspective for the development of anti-inflammatory drugs for AD early treatment."

Journal • Alzheimer's Disease • CNS Disorders • Inflammation • HLA-C • HLA-DRB1 • IL6 • TGFB1

Mitochondrial-uncoupling nanomedicine for self-heating and immunometabolism regulation in cancer cells. (PubMed, Biomaterials) - "Herein, a CD44-targeted and thermal-responsive nanocarrier was developed for the simultaneous delivery of 2,4-dinitrophenol and syrosingopine...The synergistic effects of endogenous hyperthermia and immunometabolism regulation by this nanomedicine have potential to enhance tumor immunogenicity, reshape the tumour immune microenvironment, and effectively suppress the growth of subcutaneous tumours and patient-derived organoids in triple-negative breast cancer. Therefore, the endogenous hyperthermia strategy developed in this study would revolutionize hyperthermia for cancer treatment."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Enhanced glycolysis causes extracellular acidification and activates acid-sensing ion channel 1a in hypoxic pulmonary hypertension. (PubMed, Am J Physiol Lung Cell Mol Physiol) - "Additionally, we found that intracellular alkalization and extracellular acidification occur in PASMC following CH, and in vitro hypoxia, which was prevented by inhibition of glycolysis with 2-deoxy-D-glucose (2-DG)...Although the putative monocarboxylate transporter 1 (MCT1) and -4 (MCT4) inhibitor, syrosingopine, prevented the pH shift; the specific MCT1 inhibitor, AZD3965, and/or the MCT4 inhibitor, VB124, were without effect, suggesting syrosingopine targets the glycolytic pathway independent of H+ export...These data suggest multiple H+ transport mechanisms contribute to extracellular acidosis and inhibiting glycolysis, rather than specific H+ transporters, more effectively prevents extracellular acidification and ASIC1a activation. Together, these data reveal a novel pathologic relationship between glycolysis and ASIC1a activation in hypoxic PHTN."

Journal • Cardiovascular • Hypertension • Metabolic Disorders • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • CA9 • SLC16A1

Syrosingopine and UK5099 synergistically suppress non-small cell lung cancer by activating the integrated stress response. (PubMed, Cell Death Dis) - "Importantly, our findings suggested that the synergistic suppression of NSCLC by syrosingopine and UK-5099 was dependent on ISR activation. In summary, our study proposed a promising therapeutic approach that involved the combination of Syrosingopine and UK-5099 to activate ISR, significantly hindering NSCLC growth and proliferation."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

INFLUENCE OF A PROINFLAMMATORY ENVIRONMENT ON THE EXPRESSION OF RECEPTORS OR TRANSPORTERS OF THE METABOLITES LACTATE AND SUCCINATE IN PATHOPHYSIOLOGICAL EFFECTOR CELLS IN RHEUMATOID ARTHRITIS (EULAR 2024) - "LPS-stimulated RASF were additionally treated with chemical inhibitors against MCT1 (AZD3965) and MCT4 (syrosingopine, preferential MCT4 inhibitor). A proinflammatory environment appears to differentially affect the expression of the transporters or receptors of lactate and succinate depending on the cell type and the proinflammatory factor. The increased MCT4 expression of RASF in comparison to SF of osteoarthritis patients might at least partially be caused by alterations of systemic LPS levels. The application of chemical MCT inhibitors is probably not suited for suppressing the LPS-induced IL-6 secretion of RASF."

Immunology • Inflammatory Arthritis • Osteoarthritis • Pain • Rheumatoid Arthritis • Rheumatology • CXCR3 • IL1B • IL6 • SUCNR1 • TNFA

Syrosingopine, an anti-hypertensive drug and lactate transporter (MCT1/4) inhibitor, activates hepatic stellate cells and exacerbates liver fibrosis in a mouse model. (PubMed, Genes Dis) - No abstract available

Journal • Preclinical • Fibrosis • Hepatology • Immunology • Liver Cirrhosis

AC-73 and Syrosingopine Inhibit SARS-CoV-2 Entry into Megakaryocytes by Targeting CD147 and MCT4. (PubMed, Viruses) - "Importantly, we found that AC-73 or syrosingopine significantly inhibits SARS-CoV-2 infection of megakaryocytes. Altogether, our data indicate AC-73 and syrosingopine as inhibitors of SARS-CoV-2 infection via CD147 and MCT4 that can be used to prevent SARS-CoV-2 binding and entry into megakaryocytes, which are precursors of platelets involved in COVID-19-associated coagulopathy."

Journal • Hematological Disorders • Infectious Disease • Inflammation • Novel Coronavirus Disease • Respiratory Diseases • BSG • CD34

Syrosingopine Enhances 20S Proteasome Activity and Degradation of α-Synuclein. (PubMed, J Nat Prod) - "Among them, syrosingopine was the most potent activator of the 20S proteasome and enhanced the degradation of fluorogenic substrates and α-synuclein, an IDP. Furthermore, in HeLa cells, syrosingopine enabled the binding of a membrane-permeable fluorescent probe to the catalytic site of the 20S proteasome by opening the gate."

Journal • CNS Disorders • Targeted Protein Degradation

A COMPARATIVE ANALYSIS OF METABOLIC FLEXIBILITY IN OSTEOSARCOMA CELLS (CTOS 2023) - "We later tested the effects of lactate transport inhibition with monocarboxylate transporters MCT1 +/- MCT4 inhibitors AZD3965 and syrosingopine in combination with carboplatin chemotherapy, and found that syrosingopine, but not AZD3965 significantly reduced cell viability. Collectively, our results suggest that coordinate regulation of lactate metabolism in OS fulfills a metabolic gap in respiration to assist in aerobic cancer survival, and that targeted metabolic inhibitors may synergise with chemotherapy. Furthermore, metastatic OS cells appear to be more energetic and energetically flexible than primary OS cells and mesenchymal cells. Together, these and future investigations into the metabolic landscape of OS may lead to future clinical applications for OS patients."

Oncology • Osteosarcoma • Sarcoma • Solid Tumor

Endothelial Cells Regulate Post-Ischemic Kidney Repair Through PHD/HIF-Dependent Hyperglycolysis (KIDNEY WEEK 2023) - "Ischemia-reperfusion injury (IRI) was induced by uni-/bilateral renal artery clamping, and tamoxifen treatment was started at day 1 post IRI, followed by analysis at day 14. Compared to Cre- controls, day 14 post IRI kidneys of PHD TiEC showed significant upregulation of profibrotic genes Loxl2, Tgfβ1, and Acta2, increased collagen deposition (n=6-8, p≤0.05), higher tubular injury, and reduced capillary density...Notably, post-ischemic administration of the dual MCT4/MCT1 inhibitor Syrosingopine (Syro) attenuated kidney injury in PHD TiEC mice (n=4, P≤0.5). In summary, endothelial PHDs regulate post-ischemic kidney repair through HIF-dependent mechanisms. Furthermore, our studies identify the endothelial MCT4 as a potential target for renoprotective therapies."

Acute Kidney Injury • Cardiovascular • Fibrosis • Immunology • Nephrology • Renal Disease • Reperfusion Injury • ACTA2 • CDH5 • ICAM1 • SLC16A3 • TGFB1 • VCAM1

An engineered nanoplatform cascade to relieve extracellular acidity and enhance resistance-free chemotherapy. (PubMed, J Control Release) - "The P-S-Z NPs selectively accumulate in tumors and then regulate the release of S-Z NPs containing syrosingopine (Syr) and acid-activated prodrug ZMC1-Pt depending on the extracellular acidity...As a proof of concept, this is a promising strategy to transfer the adverse effect of intracellular acidosis to facilitate chemotherapy. This well-designed delivery system effectively kills tumor cells without causing significant tumor drug resistance, thus opening a new window to treat cancer."

Journal • Metabolic Disorders • Oncology