syrosingopine / Generic mfg. - LARVOL DELTA

MCT Inhibition Targets Cervical Cancer in Lactate Enriched Microenvironments (ASTRO 2026) - "Our data shows that lactate fueled tumors exhibit more aggressive growth in vivo and are radiation resistant. In addition, our data supports that MCT 1 and 4 inhibitor, syrosingopine, reduces cell viability and tumor volume in lactate supplemented models. As we learn more about the interactions between Lactobacilli and tumors this data may provide an avenue to target treatment resistant cervical cancers."

Cervical Cancer • Oncology • Solid Tumor

Tumor microenvironment-responsive manganese nanoplatform amplifies cGAS-STING via metabolic-metal synergy for immunotherapy. (PubMed, J Control Release) - "Herein, we designed glutathione (GSH)-sensitive nanoparticles (NPMn/Syro) co-loaded with TPE-Mn and the monocarboxylate transporter 1/4 (MCT1/4) inhibitor syrosingopine (Syro) at an optimized ratio to simultaneously remodel tumor metabolism and activate innate immunity...Furthermore, combined with anti-PD-1 antibody (α-PD-1), NPMn/Syro exerts synergistic antitumor efficacy, providing a promising therapeutic strategy for clinical management of tumor. This work presents a metabolic-metal synergistic strategy to augment the cGAS-STING pathway activation and significantly reverse metabolism-mediated immunosuppressive TME."

Biomarker • Journal • Metabolic Disorders • Oncology • CGAS • SLC16A1 • STING

A pH-responsive liposomal nanoplatform for reprogramming lactate metabolism and immunogenic activation in pancreatic cancer. (PubMed, Biomaterials) - "S&P@RL co-delivers Polyphyllin VI (PPVI), which induces pyroptosis, immunogenic cell death (ICD), and STING activation, and Syrosingopine (Syro), an MCT4 inhibitor that blocks lactate efflux...Notably, S&P@RL sensitized pancreatic cancer to PD-1 blockade, effectively converting immunologically "cold" tumors into "hot" tumors without systemic toxicity. This study establishes a biomaterial-enabled strategy that integrates metabolic reprogramming and immune activation to overcome immune resistance in pancreatic cancer."

Journal • Oncology • Pancreatic Cancer • Solid Tumor • STING

Mesoporous polydopamine nanoplatform enhances IL-2 immunotherapy for hepatocellular carcinoma via mild photothermal therapy and lactate regulation. (PubMed, Asian J Pharm Sci) - "Here, we developed a nano-immunotherapy platform (Syr/IL-2@MPDA) using mesoporous polydopamine (MPDA) nanoparticles co-loaded with His-tagged IL-2 and the monocarboxylate transporter inhibitor Syrosingopine (Syr)...In an orthotopic N1S1 HCC rat model, the treatment demonstrated strong therapeutic efficacy in combination with αPD-L1 and TAE, overcoming the hazards of TAE-induced lactate accumulation and immune suppression. Overall, this study demonstrates a safe and effective strategy that enhances IL-2 immunotherapy through mPTT and metabolic modulation, offering a promising combination treatment for advanced HCC."

Journal • Hepatocellular Cancer • Oncology • Solid Tumor • CD8 • IL2

Syrosingopine enhances immune checkpoint blockade efficacy by inhibition of MCTs and metabolic reprogramming in triple-negative breast cancer. (PubMed, Biochim Biophys Acta Mol Basis Dis) - "In immunocompetent TNBC models, syrosingopine synergized with anti-PD-1 to suppress tumor growth, remodel the immune landscape, and prolong survival, while genetic perturbation of MCTs recapitulated key metabolic and immunologic phenotypes. These findings identify tumor lactate export as an important metabolic barrier to antitumor immunity in TNBC and support MCT-targeted lactate transport inhibition as a promising strategy to reprogram the TME and improve immunotherapeutic efficacy."

Checkpoint inhibition • Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD8 • PD-L1

Repurposing Syrosingopine for Cancer Therapy: Lactate Trapping and ISR Sensitization as Metabolic Vulnerabilities. (PubMed, Oncol Ther) - "Syrosingopine exemplifies a preclinical "lactate trap"-based metabolic intervention with the potential to modulate integrated stress responses and immunometabolic pathways in glycolysis-dependent tumors. Its successful clinical repurposing will require biomarker-guided early-phase trials, optimization of nanoformulations and dosing strategies, incorporation of metabolic imaging readouts, and careful safety monitoring to address tissue-specific toxicities and metabolic plasticity. Graphical abstract available for this article."

Journal • Review • Cardiovascular • Fibrosis • Immunology • Liver Cirrhosis • Oncology

Lactate-mediated NK cell dysfunction as a prognostic marker and therapeutic target in breast cancer. (PubMed, Cell Death Discov) - "Pharmacologic inhibition of lactate transport, via Syrosingopine or MSC-4381 and AZD3965 combination, restored NK cell cytotoxicity in tumor co-cultures, as shown by increased NK cell degranulation, caspase-3/7-mediated tumor apoptosis, and spheroid shrinkage. Finally, GPR81 deletion mirrored these effects, enhancing NK cell activity. These findings identify lactate as a driver of NK cell suppression and highlight lactate transport and receptor targeting as a strategy to enhance NK cell-based immunotherapies in breast cancer and other lactate-rich tumors."

Biomarker • IO biomarker • Journal • Breast Cancer • Oncology • Solid Tumor • CASP3 • CASP7 • CXCL10 • CXCL9

In Silico and In Vitro Analysis of Ganoderic Acid A Binding to Human Monocarboxylate Transporters 1 and 4. (PubMed, Proteins) - "Molecular docking and molecular dynamics simulations using the known dual inhibitor syrosingopine as a reference indicated that GAA can associate with both MCT1 and MCT4...Notably, ITDRF analysis revealed enhanced stability of a higher-molecular-weight MCT4, suggesting a biphasic binding behavior. Together, these findings indicate that GAA directly interacts with MCT1 and MCT4, and uncovers a biphasic binding pattern associated with MCT4."

Journal • Preclinical • Oncology

A Biomimetic Microparticle Disrupting the Intracellular/Extracellular pH Homeostasis of Tumor Cells for Cancer Chemo-Immunotherapy. (PubMed, ACS Nano) - "Herein, we developed a biomimetic tumor cell-derived microparticle for tumor-targeted codelivery of syrosingopine (Syr) and doxorubicin prodrug (Dox-EMCH). The increased intracellular acidity activates Dox-EMCH to induce immunogenic cell death, while the alleviated acidity outside tumor cells modulates the immunosuppressive tumor microenvironment (TME) by restoring the activities of cytotoxic T lymphocytes and natural killer cells, promoting M1-like macrophage polarization, and inhibiting regulatory T cells. As a result, the biomimetic microparticles initiate orchestrated chemotherapy and immunotherapy for effective tumor suppression by disrupting the intracellular and extracellular pH balance in tumor tissues."

Journal • Oncology

Harnessing biomimetic nano-regulators for in situ photothermia and lactate regulation to amplify cuproptosis immunotherapy. (PubMed, Biomaterials) - "To address this, we develop a biomimetic copper-based nanoplatform (SCTDM) coated with macrophage-tumor cell hybrid membranes (HM) and co-loaded with the lactate modulator syrosingopine (Su3118) and the copper ionophore disulfiram (DSF). Collectively, the synergistic combination of PTT and lactate metabolism modulation serves to potentiate cuproptosis-induced immunogenic cell death. This cascade effect culminates in the reprogramming of the immunosuppressive TME and augments anti-tumor immunity for eradicating primary tumors and preventing recurrence."

Journal • Colorectal Cancer • Oncology • Solid Tumor

Lactylome-based investigation of osteoarthritic subchondral bone reveals cell-specific differential expression of histone H4K12 lactylation: an experimental study. (PubMed, Int J Surg) - "This study delineates a lactate-epigenetic axis in which osteoclast-derived lactate, transported via MCT1/MCT4, enters osteoblasts and activates osteogenic transcriptional programs through H4K12la, driving osteogenic activation and subchondral sclerosis. These findings provide novel insights into the molecular basis of subchondral bone remodeling in OA and suggest potential therapeutic targets involving lactate metabolism, lactate transport, and H4K12la-mediated epigenetic regulation to modulate OA-related subchondral bone remodeling."

Journal • Immunology • Osteoarthritis • Pain • Rheumatology

Lactylation-driven nuclear RIG-I promoted by lactate transporter inhibitor suppresses DNA damage repair through inhibiting PARP1 activity. (PubMed, Cell Rep) - "Syrosingopine treatment sensitizes LUAD cells to PARP inhibitor (PARPi) and potentiates the therapeutic efficacy of olaparib in a mouse LUAD model. Altogether, our study reveals that lactylation drives RIG-I nuclear function to inhibit DNA damage repair via PARP suppression. This supports the potential co-administration of syrosingopine and PARPi for LUAD treatment."

Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • DDX58

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