- |||||||||| AZD-3965 / Cancer Research UK
Journal: Gastric cancer cells shuttle lactate to induce inflammatory CAF-like phenotype and function in bone marrow-derived mesenchymal stem cells. (Pubmed Central) - Jun 9, 2025
Herein, exogenous lactate induced a pro-tumorigenic phenotype in BM-MSCs, which was blocked by AZD3965...Collectively, gastric cancer cells induce an iCAF-like phenotype and function in BM-MSCs through a lactate shuttle mechanism, emphasizing the role of metabolic reprogramming in cellular communication that fosters a supportive tumor microenvironment. Targeting lactate-related pathways may provide new therapeutic strategies to hinder BM-MSCs' supportive roles in gastric cancer.
- |||||||||| NXE0039732 / Nxera Pharma
Trial completion date, Trial primary completion date, Monotherapy: HTL0039732 in Participants With Advanced Solid Tumours (clinicaltrials.gov) - Jun 9, 2025
P1/2, N=150, Recruiting,
Targeting lactate-related pathways may provide new therapeutic strategies to hinder BM-MSCs' supportive roles in gastric cancer. Trial primary completion date: Sep 2026 --> Jun 2027 | Trial completion date: Sep 2026 --> Jun 2027
- |||||||||| RITA / Aprea, AZD-3965 / Cancer Research UK
Journal: Cr (VI) induces lactate utilization through HIF-1?/MCT1 dependent on p53 protein level. (Pubmed Central) - Jun 5, 2025
inhibitor YC-1 and MCT1 inhibitor AZD3965 suppressed Cr (VI)-induced lactate utilization and cell growth...These findings highlighted the role of p53 protein level in the effects of Cr (VI) on HIF-1?/MCT1 to induce lactate utilization and cell growth. Targeting the p53/HIF-1?/MCT1 pathway could inhibit Cr (VI)-mediated tumorigenesis.
- |||||||||| AZD-3965 / Cancer Research UK
Journal: Lactate induces oxidative phosphorylation in osteoblasts via Gpr81-Stat3 signaling. (Pubmed Central) - May 30, 2025
Inhibition of Gpr81 by 3-OBA or decrease in Gpr81 expression by Gpr81 siRNA, but not the interruption of MCT1 by AZD3965, led to the inhibition of the Gpr81-Jak2-Stat3-Y705 and Gpr81-Akt-Stat3-S727 signaling, and OXPHOS and cell differentiation of MC3T3-E1 cells were also inhibited...Lastly, osteoblast GPR81-deficient mice showed lower bone formation. Thus, these findings propose a novel signaling mechanism by which lactate regulates cell differentiation as well as OXPHOS through the activation of Stat3 signaling by Gpr81.
- |||||||||| azemiglitazone (MSDC-0602K) / Cirius Therap, AZD-3965 / Cancer Research UK, mitoglitazone (MSDC-0160) / Metabolic Solutions
Journal: Glyceraldehyde-3-Phosphate Dehydrogenase/1,3-Bisphosphoglycerate-NADH as Key Determinants in Controlling Human Retinal Endothelial Cellular Functions: Insights from Glycolytic Screening. (Pubmed Central) - May 30, 2025
Pharmacological inhibitors targeting lower glycolytic components were tested: heptelidic acid for glyceraldehyde-3-phosphate dehydrogenase (GAPDH), NG-52 for phosphoglycerate kinase (PGK), shikonin for pyruvate kinase M (PKM), galloflavin for lactate dehydrogenase (LDH), AZD3965 for lactate transporter (MCT1), and MSDC-0160 for the mitochondrial pyruvate carrier (MPC)...GAPDH and its downstream products (1,3-BPG and NADH) are shown to play a pivotal role in maintaining barrier integrity and promoting HREC adhesion and spreading. These findings guide the development of targeted interventions that modulate HREC bioenergetics to treat endothelial dysfunction in various retinal disorders, while minimizing potential adverse effects on healthy endothelial cells.
- |||||||||| bortezomib / Generic mfg., AZD-3965 / Cancer Research UK, syrosingopine / Generic mfg.
Journal: Mitochondrial fission factor drives an actionable metabolic vulnerability in multiple myeloma. (Pubmed Central) - May 22, 2025
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.
- |||||||||| IMA950 / Immatics, University Hospitals of Geneva
Trial completion: IMA950-106: Pembrolizumab in Association With the IMA950/Poly-ICLC for Relapsing Glioblastoma (clinicaltrials.gov) - May 13, 2025
P1/2, N=18, Completed,
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. Active, not recruiting --> Completed
- |||||||||| AZD-3965 / Cancer Research UK
Journal: Lactic acid inhibits the interaction between PD-L1 protein and PD-L1 antibody in the PD-1/PD-L1 blockade therapy-resistant tumor. (Pubmed Central) - May 1, 2025
Furthermore, we showed that the combination therapy of targeting PD-L1 with our PD-L1 antibody-drug conjugate (PD-L1-ADC) and reducing lactic acid with the monocarboxylate transporter 1 (MCT-1) inhibitor, AZD3965, can effectively treat the PD-1/PD-L1 blockade-resistant tumors. The findings of this study provide a new mechanism of how lactic acid induces an immunosuppressive tumor microenvironment and suggest a potential combination treatment to overcome the tumor resistance to PD-1/PD-L1 blockade therapy.
- |||||||||| AZD-3965 / Cancer Research UK
The role of tumor microenvironment lactic acid in the cancer cell resistance to anti-PD-L1 and anti-PD-1 blockade therapy (Section 39; Poster Board No: 7) - Mar 25, 2025 - Abstract #AACR2025AACR_7005;
Furthermore, we showed that the combination therapy of targeting PD-L1 with our PD-L1 antibody-drug conjugate (PD-L1-ADC) and reducing lactic acid with the MCT-1 inhibitor, AZD3965, can effectively treat the PD-1/PD-L1 blockade resistant tumors. Altogether, the findings in this study uncover a new mechanism of how lactic acid induces an immunosuppressive tumor microenvironment and suggest a potential combination treatment strategy to overcome the tumor resistance to PD-1/PD-L1 blockade therapy and improve clinical outcomes.
- |||||||||| MCT1 regulates the progression of early invasive oral squamous cell carcinoma (Section 52; Poster Board No: 20) - Mar 25, 2025 - Abstract #AACR2025AACR_6228;
Altogether, the findings in this study uncover a new mechanism of how lactic acid induces an immunosuppressive tumor microenvironment and suggest a potential combination treatment strategy to overcome the tumor resistance to PD-1/PD-L1 blockade therapy and improve clinical outcomes. Abstract is embargoed at this time.
- |||||||||| AZD-3965 / Cancer Research UK
Impact of MCT1 inhibition on NSCLC metabolism and sensitivity to therapy (Section 14; Poster Board No: 20) - Mar 25, 2025 - Abstract #AACR2025AACR_4671;
Metabolic reprogramming in NSCLC leads to the use of alternate carbon sources, such as lactate, and this can be modeled in both standard and physiologic culture conditions. Notably, this does not appear to be a general sensitization to cell death.
- |||||||||| VTP-600 / Barinthus Bio
Enrollment change, Trial completion date, Trial primary completion date, Checkpoint inhibition: CRUKD/20/001: A Trial of ChAdOx1 and MVA Vaccines Against MAGE-A3 and NY-ESO-1 (clinicaltrials.gov) - Mar 18, 2025
P1/2, N=15, Suspended,
Notably, this does not appear to be a general sensitization to cell death. N=103 --> 15 | Trial completion date: Dec 2027 --> Oct 2026 | Trial primary completion date: Dec 2027 --> Sep 2024
- |||||||||| AZD-3965 / Cancer Research UK
Journal: Lactate dehydrogenase B deficiency-dependent hyperlactatemia coordinates with necroptosis to worsen septic liver and kidney injuries. (Pubmed Central) - Mar 6, 2025
Blockade of necroptosis significantly protects Ldhb-/- mice against septic liver and kidney injuries, enabling a compensation towards the therapeutic efficacy of AZD3965. Our study together unearth the coordination of hyperlactatemia and necroptosis in septic liver and kidney injuries in the context of LDHB deficiency, and support further investigation of combined targeting SLC16A1 and necroptosis for clinical treatment of sepsis with low LDHB activity.
- |||||||||| MOv18 IgE / Epsilogen, Cancer Research UK
Biomarker, Journal: Systematic mutational analysis reveals an essential role of N275 in IgE stability. (Pubmed Central) - Nov 13, 2024
However, the ongoing clinical trial of MOv18 IgE has highlighted the potential of using IgE antibodies in cancer therapy...In summary, our study unveils an intricate relationship between N-glycosylation sites and the structural-functional dynamics of IgE antibodies. Furthermore, it offers novel insights into the IgE scaffold, paving the way for the development of more effective and stable IgE-based therapeutics.
- |||||||||| doxorubicin hydrochloride / Generic mfg.
Journal: 2-[18F]Fluoropropionic Acid PET Imaging of Doxorubicin-induced Cardiotoxicity. (Pubmed Central) - Nov 1, 2024
Co-administration of [ 18 F]FPA and AZD3965 enhanced the imaging contrast of the diseased heart while reducing overall exposure to radioactivity. Conclusions [ 18 F]FPA, especially when co-administered with AZD3965, is a new tool for imaging changes in fatty acid metabolism occurring in response to doxorubicin-induced cardiomyopathy by PET.
- |||||||||| AZD-3965 / Cancer Research UK
Journal: Emodin regulated lactate metabolism by inhibiting MCT1 to delay non-small cell lung cancer progression. (Pubmed Central) - Oct 28, 2024
In vivo experiments had shown that emodin and AZD3965 could effectively inhibit the growth of lung cancer and inhibit the expression of MCT1. All in all, our data suggested that emodin inhibited the proliferation, migration, and invasion of lung cancer cells, possibly by inhibiting MCT1, providing important theoretical basis for elucidating the mechanism of emodin in treating lung cancer.
- |||||||||| MK-0752 / Merck (MSD)
Biomarker, Journal, BRCA Biomarker: Molecular analysis of BRCA1 and BRCA2 genes in La Rioja (Spain): five new variants. (Pubmed Central) - Oct 23, 2024
The spectrum of pathogenic variants in the BRCA1/2 genes in La Rioja is similar to that in other Spanish regions, with some unique characteristics. The pathogenic c.6024dupG variant in the BRCA2 gene was detected in a large number of families and could have a founding effect in the Ebro riverside areas in the regions of La Rioja and Navarra.
- |||||||||| budoprutug (TNT119) / Eliem Therap
Enrollment change, Trial withdrawal: Phase 1b/2a in SLE With Budoputug (clinicaltrials.gov) - Oct 16, 2024
P1/2, N=0, Withdrawn,
The pathogenic c.6024dupG variant in the BRCA2 gene was detected in a large number of families and could have a founding effect in the Ebro riverside areas in the regions of La Rioja and Navarra. N=40 --> 0 | Not yet recruiting --> Withdrawn
- |||||||||| AZD-3965 / Cancer Research UK
Journal: Transcriptome analysis of anaerobic glycolysis effects on Jurkat T cell proliferation. (Pubmed Central) - Oct 9, 2024
The monocarboxylate transporter 1 inhibitor AZD3965 was used to target and block the transmembrane transport of lactate, thereby inhibiting anaerobic glycolysis in Jurkat T cells...Anaerobic glycolysis contributes to the regulation of Jurkat T-cell proliferation. The underlying mechanism may involve the estrogen signaling pathway or PI3K-Akt signaling pathway as well as protein metabolism.
- |||||||||| AZD-3965 / Cancer Research UK
Development of [18F]-labelled lactate for oxidative cancer imaging (e-Poster Area) - Sep 27, 2024 - Abstract #EANM2024EANM_2505;
This possibility is currently tested with slowly growing PC3 tumours and metastases in mice. [18F]-FLac could further be used alone or sequentially with 18FDG as a companion diagnostic for personalized treatments selectively targeting oxidative or glycolytic cancer cells.
- |||||||||| DCVax-L (autologous dendritic cell vaccine leaded with autologous tumor cell lysate) / Northwest Biotherap, SurVaxM (SVN53-67/M57-KLH peptide vaccine) / MimiVax, IMA950 / Immatics, University Hospitals of Geneva
Immunotherapeutic Advances in Glioma Management: The Rise of Vaccine-Based Approaches (Hall 5) - Sep 24, 2024 - Abstract #EANO2024EANO_275;
Challenges in assessing vaccine efficacy and addressing treatment-related adverse effects emphasise the need for further research and clinical trials. Challenges like tumour heterogeneity and immune evasion persist, but advances in genetic engineering and immunotherapy offer hope for enhancing vaccine efficacy.
- |||||||||| AZD-3965 / Cancer Research UK
Role of electrogenic and electroneutral monocarboxylate transport in airway clearance () - Sep 4, 2024 - Abstract #NACFC2024NACFC_913;
Mucociliary clearance (PTS and MTV) is not affected by SMCT1 activity, although MCT activity increases mucociliary clearance, possibly because removal of H+ from ASL alkalizes the airway surface. The use of MCT transportable substrates might help alleviate mucostasis in muco-obstructive diseases and will be tested in animal models of these diseases.
- |||||||||| CRT0066101 / Cancer Research UK
Journal: Pharmacological inhibition of protein kinase D2/Aurora kinase A signalling axis suppresses G2/M cell cycle progression and proliferation of epithelial ovarian cancer cells. (Pubmed Central) - Aug 7, 2024
We show that PKD2 is activated during G2/M cell cycle transition and its catalytic inactivation by small molecule inhibitor CRT0066101 or genetic knockdown caused suppression of EOC cell proliferation followed by a delay into mitotic entry...Moreover, pharmacological inhibition of Aurora kinase A by small molecule CD532 or its shRNA-mediated genetic knockdown suppressed EOC cell proliferation, induced G2/M cell cycle arrest and mitotic catastrophe followed by apoptosis. Taken together, our results indicated that PKD2 positively regulates Aurora kinase A during G2/M cell cycle entry and pharmacological targeting of PKD2/Aurora kinase A signalling axis could serve as a novel therapeutic intervention against a lethal pathology like EOC.
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