- |||||||||| telaglenastat (CB-839) / Calithera
Journal, IO biomarker: Hafnium Metal-Organic Framework-Based Glutamine Metabolism Disruptor For Potentiating Radio-Immunotherapy in MYC-Amplified Hepatocellular Carcinoma. (Pubmed Central) - Apr 3, 2025 In this work, a hafnium-based metal-organic framework (Hf-MOF), UiO-66-Hf(2OH)-CB-839/BSO@HA (UiO-66-Hf(2OH)-C/B@HA), was designed to codeliver telaglenastat (CB-839) and buthionine sulfoximine (BSO), which synergistically inhibited glutamine metabolism and alleviated tumor hypoxia...In the orthotopic HCC model, established with MYC-amplified tumor cells, intravenous administration of UiO66-Hf(2OH)-C/B@HA significantly potentiated the efficacy of radio-immunotherapy, resulting in superior tumor regression. In summary, our study provides insights into the design of Hf-MOF for radio-immunotherapy and proposes a promising therapeutic approach for MYC-amplified HCC.
- |||||||||| telaglenastat (CB-839) / Calithera
Journal: CircPVT1 weakens miR-33a-5p unleashing the c-MYC/GLS1 metabolic axis in breast cancer. (Pubmed Central) - Mar 21, 2025 In summary, our study provides insights into the design of Hf-MOF for radio-immunotherapy and proposes a promising therapeutic approach for MYC-amplified HCC. In aggregate, our findings unveil the circPVT1/miR-33a-5p/Myc/GLS1 axis as a pro-tumorigenic metabolic event sustaining breast cancer transformation with potential therapeutic implications.
- |||||||||| telaglenastat (CB-839) / Calithera, Tagrisso (osimertinib) / AstraZeneca
Trial completion date, Trial primary completion date: Telaglenastat Hydrochloride and Osimertinib in Treating Patients With EGFR-Mutated Stage IV Non-small Cell Lung Cancer (clinicaltrials.gov) - Mar 18, 2025 P1/2, N=23, Active, not recruiting, In aggregate, our findings unveil the circPVT1/miR-33a-5p/Myc/GLS1 axis as a pro-tumorigenic metabolic event sustaining breast cancer transformation with potential therapeutic implications. Trial completion date: Jun 2025 --> Mar 2026 | Trial primary completion date: Jun 2025 --> Jun 2024
- |||||||||| mivavotinib (CB-659) / Calithera, entospletinib (GS-9973) / Kronos Bio, Tavalisse (fostamatinib) / Rigel
Journal: Gene Expression Profiling in Acute Myeloid Leukemia Patient Subgroups With High and Low Sensitivity Toward SYK Inhibitors. (Pubmed Central) - Mar 16, 2025 Gene set enrichment analysis further highlighted that high-sensitivity patient samples were upregulated in pathways associated with oxidative phosphorylation and MYC targets, whereas low-sensitivity patient samples showed enrichment in TGF beta signaling and IL6 JAK STAT3 signaling. These results identify gene expression profile signatures that may predict sensitivity to SYK inhibition and underscore the potential for personalized therapeutic strategies in AML.
- |||||||||| telaglenastat (CB-839) / Calithera
Journal: Immunostimulatory Hydrogel with Synergistic Blockage of Glutamine Metabolism and Chemodynamic Therapy for Postoperative Management of Glioblastoma. (Pubmed Central) - Feb 20, 2025 The methodology entails crafting injectable gel scaffolds with short peptide molecules, incorporating the glutaminase inhibitor CB-839 and copper peptide self-assembled particles (Cu-His NPs) renowned for their chemodynamic therapy (CDT) efficacy...This dual mechanism culminates in augmented immunogenic cell death within glioblastoma multiforme cells and improves a conducive immune microenvironment. Based on the concept of metabolic reprogramming, this treatment strategy has great potential to significantly reduce GBM tumor recurrence and prolong median survival in murine models.
- |||||||||| telaglenastat (CB-839) / Calithera
Journal, IO biomarker: Effect of repurposed metabolic drugs on human macrophage polarization and antitumoral activity. (Pubmed Central) - Feb 19, 2025 This study reveals that targeting glutamine metabolism with CB839 effectively blocks the IL-4-induced anti-inflammatory phenotype in macrophages and enhances their tumor-killing capability. Our results provide a compelling rationale for repurposing metabolic drugs to create a pro-inflammatory tumor microenvironment, thereby potentially enhancing the efficacy of current immunotherapies.
- |||||||||| Journal: Ursodeoxycholic acid inhibits the uptake of cystine through SLC7A11 and impairs de novo synthesis of glutathione. (Pubmed Central) - Feb 4, 2025
Together, UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity, and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA. More importantly, in combination with other antitumor chemotherapy or physiotherapy treatments, UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.
- |||||||||| everolimus / Generic mfg., sapanisertib (CB-228) / Calithera, serabelisib (MLN1117) / Takeda
Journal, PD(L)-1 Biomarker, IO biomarker: Enhancing immunotherapy through PD-L1 upregulation: the promising combination of anti-PD-L1 plus mTOR inhibitors. (Pubmed Central) - Jan 8, 2025 These preclinical findings suggest that mTOR inhibition with TAK-228 can increase PD-L1 levels, potentially impacting the specific immune response against UC cells. This highlights the rationale for exploring the combination of mTOR inhibitors with ICIs in patients with advanced UC.
- |||||||||| telaglenastat (CB-839) / Calithera
Trial completion date, Trial primary completion date, Metastases: Glutaminase Inhibition and Chemoradiation in Advanced Cervical Cancer (clinicaltrials.gov) - Nov 18, 2024 P2, N=42, Not yet recruiting, Trial completion date: Jan 2025 --> Jan 2026 | Trial primary completion date: Jan 2025 --> Jan 2026 Trial completion date: Jan 2031 --> Apr 2031 | Trial primary completion date: Jan 2031 --> Apr 2031
- |||||||||| telaglenastat (CB-839) / Calithera, Promacta (eltrombopag) / Novartis
Developing a Therapeutic Strategy for Targeting Metabolic Vulnerability of TET2 Mutant Leukemia (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_2721; This discovery paves the way for a biomarker-driven, novel therapeutic strategy for myeloid leukemia. Furthermore, our research highlights the potential of combining TET2 inhibitors with glutaminolysis inhibitors as a pioneering treatment approach for a broad range of leukemia types.
- |||||||||| numidargistat (INCB001158) / Calithera
Journal: Establishing Gene Expression and Knockout Methods in Esteya vermicola CBS115803. (Pubmed Central) - Oct 13, 2024 Moreover, we successfully implemented a split-marker strategy to delete the EvIPMD gene in E. vermicola CBS115803. In summary, our findings present valuable experimental methodologies for gene function analysis in E. vermicola CBS115803.
- |||||||||| telaglenastat (CB-839) / Calithera
Preclinical, Journal: Glutaminolysis provides nucleotides and amino acids to regulate osteoclast differentiation in mice. (Pubmed Central) - Oct 11, 2024 Highlighting the therapeutic implications of these findings, inhibiting glutaminolysis using CB-839 prevented ovariectomy induced bone loss in mice. Collectively, our data provide strong genetic and pharmacological evidence that glutaminolysis is essential to regulate osteoclast metabolism, promote osteoclastogenesis and modulate bone resorption in mice.
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, telaglenastat (CB-839) / Calithera, IPN60090 / UT MD Anderson Cancer Center, Ipsen
Journal, IO biomarker: Glutaminase 1 plays critical roles in myelodysplastic syndrome and acute myeloid leukemia cells. (Pubmed Central) - Sep 20, 2024 Cells transfected with GLS1 short hairpin RNA showed suppressed proliferation under hypoxic conditions and increased sensitivity to venetoclax. Targeting glutaminolysis and BCL2 inhibition enhances the therapeutic efficacy and has been proposed as a novel strategy for treating high-risk MDS and AML.
- |||||||||| sapanisertib (CB-228) / Calithera
Trial completion, Trial completion date, Trial primary completion date: DICE: Dual mTorc Inhibition in advanCed/Recurrent Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Cancer (of Clear Cell, Endometrioid and High Grade Serous Type, and Carcinosarcoma) (clinicaltrials.gov) - Sep 20, 2024 P2, N=134, Completed, Targeting glutaminolysis and BCL2 inhibition enhances the therapeutic efficacy and has been proposed as a novel strategy for treating high-risk MDS and AML. Active, not recruiting --> Completed | Trial completion date: Dec 2022 --> Nov 2023 | Trial primary completion date: Dec 2022 --> Nov 2023
- |||||||||| telaglenastat (CB-839) / Calithera
Journal, Tumor cell: CB-839 Induces Reversible Dormancy in Lung Tumor-cells. (Pubmed Central) - Sep 15, 2024 In hypoxic conditions, CB-839's effect on clonogenic survival was amplified in a dose dependent manner consistent with increased role of GLS1 for energy production under hypoxic conditions. In conclusion, these results suggest CB-839 efficacy is linked to temporary and reversible reduction in glutamine utilization suggesting induction of dormancy.
- |||||||||| telaglenastat (CB-839) / Calithera
Journal: A Ketogenic Diet Sensitizes Pancreatic Cancer to Inhibition of Glutamine Metabolism. (Pubmed Central) - Sep 1, 2024 As a result, glutamine metabolism inhibitors, such as DON and CB839 in combination with a ketogenic diet had robust anti-cancer effects. These findings provide rationale to study the use of a ketogenic diet with glutamine targeted therapies in a clinical context.
- |||||||||| sapanisertib (CB-228) / Calithera
Journal: ?-sitosterol alleviates atherosclerosis by regulating catalase. (Pubmed Central) - Aug 21, 2024 In vitro experiments showed that ?-sitosterol can inhibit lipid deposition and phenotypic transformation of vascular smooth muscle cells (VSMCs). However, knocking down catalase (CAT), the direct target of ?-sitosterol, not only promoted lipid deposition and phenotypic transformation of VSMCs, but also activated the PI3K/Akt/mTOR pathway, and the mTOR inhibitor (ink-128) can eliminate the effect of CAT knockdown, suggesting that ?-sitosterol may inhibit lipid deposition and phenotypic transformation of VSMCs by activating CAT and silencing the PI3K/Akt/mTOR signaling pathway, thereby alleviating atherosclerosis.
- |||||||||| Tagrisso (osimertinib) / AstraZeneca
Journal: The combined inhibition of SLC1A3 and glutaminase in osimertinib-resistant EGFR mutant cells. (Pubmed Central) - Aug 18, 2024 However, knocking down catalase (CAT), the direct target of ?-sitosterol, not only promoted lipid deposition and phenotypic transformation of VSMCs, but also activated the PI3K/Akt/mTOR pathway, and the mTOR inhibitor (ink-128) can eliminate the effect of CAT knockdown, suggesting that ?-sitosterol may inhibit lipid deposition and phenotypic transformation of VSMCs by activating CAT and silencing the PI3K/Akt/mTOR signaling pathway, thereby alleviating atherosclerosis. Targeting glutaminase and glutamic acid may overcome the osimertinib-resistant EGFR-mutant lung cancer.
- |||||||||| telaglenastat (CB-839) / Calithera, Farydak (panobinostat) / Secura Bio
Journal, Combination therapy: Inhibition of glutaminolysis alone and in combination with HDAC inhibitor has anti-myeloma therapeutic effects. (Pubmed Central) - Jul 26, 2024 Glutaminolysis contributes to the viability of MM cells, and the GLS inhibitor CB-839 has been proven to be an effective treatment for enhancing the cytotoxic effect of HDAC inhibition. These results are clinically relevant and suggest that CB-839 is a potential therapeutic candidate for patients with MM.
- |||||||||| telaglenastat (CB-839) / Calithera, MYCi975 / Northwestern University Feinberg School of Medicine
Journal: Therapeutic Targeting of the GLS1-c-Myc Positive Feedback Loop Suppresses Glutaminolysis and Inhibits Progression of Head and Neck Cancer. (Pubmed Central) - Jul 18, 2024 Therapeutically, combining CB-839 with the c-Myc inhibitor MYCi975 strongly suppressed GLS1-c-Myc signaling, resulting in a superior antitumor effect compared to either single agent in an orthotopic mouse model of HNSCC. These findings hold promise for the development of effective therapies for HNSCC patients, addressing an urgent need arising from the significant incidence and high metastatic rate of the disease.
- |||||||||| telaglenastat (CB-839) / Calithera, JHU083 / Johns Hopkins University, AstraZeneca
Review, Journal: Glutaminase - A potential target for cancer treatment. (Pubmed Central) - Jun 28, 2024 Earlier reports neither discuss nor provide perspectives on exact signaling gene or pathway. Hence, the present review highlights the plausible role of glutaminase in cancer and the current therapeutic approaches and clinical trials to target and inhibit glutaminase enzymes for better cancer treatment.
- |||||||||| Tagrisso (osimertinib) / AstraZeneca, sapanisertib (CB-228) / Calithera
Trial completion date, Trial primary completion date, Combination therapy, Metastases: Testing the Combination of MLN0128 (TAK-228) and AZD9291 in Advanced EGFR (Epidermal Growth Factor Receptor) Mutation Positive Non-small Cell Lung Cancer (clinicaltrials.gov) - Jun 26, 2024 P1, N=36, Active, not recruiting, Hence, the present review highlights the plausible role of glutaminase in cancer and the current therapeutic approaches and clinical trials to target and inhibit glutaminase enzymes for better cancer treatment. Trial completion date: Jun 2024 --> May 2025 | Trial primary completion date: Jun 2024 --> May 2025
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