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DRUG CLASS:

Glutamate inhibitor

Related drugs:
9d
Enrollment closed
13d
Repurposing Riluzole for Cancer-Related Cognitive Impairment: a Pilot Trial (clinicaltrials.gov)
P2, N=34, Recruiting, University of California, Irvine | Not yet recruiting --> Recruiting | Trial completion date: Sep 2026 --> Dec 2026 | Initiation date: Sep 2024 --> Dec 2024 | Trial primary completion date: Sep 2025 --> Dec 2025
Enrollment open • Trial completion date • Trial initiation date • Trial primary completion date
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BDNF (Brain Derived Neurotrophic Factor)
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riluzole
17d
Riluzole in Patients With Spinocerebellar Ataxia Type 7 (clinicaltrials.gov)
P2/3, N=34, Recruiting, S. Andrea Hospital | Unknown status --> Recruiting | Trial completion date: Jan 2021 --> Sep 2026 | Trial primary completion date: Oct 2020 --> Sep 2025
Enrollment open • Trial completion date • Trial primary completion date
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riluzole
1m
Oxaloacetate for the Improvement of Cognitive Complaints in Stage 0-IIIA Breast Cancer Survivors (clinicaltrials.gov)
P2, N=24, Recruiting, Jonsson Comprehensive Cancer Center | Trial completion date: Nov 2025 --> Nov 2026 | Trial primary completion date: Nov 2024 --> Nov 2025
Trial completion date • Trial primary completion date
2ms
RILUZOX-01: Effectiveness Assessment of Riluzole in the Prevention of Oxaliplatin-induced Peripheral Neuropathy. (clinicaltrials.gov)
P2, N=80, Suspended, UNICANCER | Trial completion date: Oct 2024 --> Mar 2025 | Active, not recruiting --> Suspended | Trial primary completion date: Sep 2024 --> Mar 2025
Trial completion date • Trial suspension • Trial primary completion date
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oxaliplatin • riluzole
2ms
BDNF augmentation reverses cranial radiation therapy-induced cognitive decline and neurodegenerative consequences. (PubMed, bioRxiv)
Moreover, riluzole (RZ)-mediated increased BDNF in vivo in the chemotherapy-exposed mice reversed cognitive decline...Dual-immunofluorescence staining, spatial transcriptomics, and biochemical assessment of RZ-treated irradiated brains demonstrated preservation of synaptic integrity and neuronal plasticity but not neurogenesis and reduced neuroinflammation concurrent with elevated BDNF levels and transcripts compared to vehicle-treated irradiated brains. In summary, oral administration of RZ represents a viable and translationally feasible neuroprotective approach against RICD.
Journal
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BDNF (Brain Derived Neurotrophic Factor)
|
riluzole
2ms
Riluzole Enhancing anti-PD-1 Efficacy by Activating cGAS/STING Signaling in Colorectal Cancer. (PubMed, Mol Cancer Ther)
This combination showed greater efficacy than either single agent, and strongly suppressed tumor growth in vivo. Taken together, our studies indicate that riluzole activates cGAS/STING-mediated innate immune responses, which might be exploited to sensitize colorectal tumors to anti-PD-1/PD-L1 therapies. .
Journal • PD(L)-1 Biomarker • IO biomarker
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CD8 (cluster of differentiation 8) • CXCL10 (Chemokine (C-X-C motif) ligand 10) • IFNB1 (Interferon Beta 1)
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CXCL10 expression
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riluzole
3ms
Riluzole and Sorafenib Tosylate in Treating Patients With Advanced Solid Tumors or Melanoma (clinicaltrials.gov)
P1, N=35, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2024 --> Sep 2025
Trial completion date • Metastases
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BCL2 (B-cell CLL/lymphoma 2)
|
sorafenib • riluzole
4ms
Repurposing Riluzole for Cancer-Related Cognitive Impairment: a Pilot Trial (clinicaltrials.gov)
P2, N=34, Not yet recruiting, University of California, Irvine
New P2 trial
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BDNF (Brain Derived Neurotrophic Factor)
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riluzole
5ms
Newly Synthesized Indolylacetic Derivatives Reduce Tumor Necrosis Factor-Mediated Neuroinflammation and Prolong Survival in Amyotrophic Lateral Sclerosis Mice. (PubMed, ACS Pharmacol Transl Sci)
Indeed, riluzole, an N-methyl-D-aspartate (NMDA) glutamate receptor blocker, and edaravone, a reactive oxygen species (ROS) scavenger, are currently the sole two medications approved for ALS treatment. In conclusion, the findings of the present work support the potential of the synthesized indolylacetic derivatives II-IV in ALS treatment. Indeed, in the attempt to realize an association between two active molecules, we assumed that the combination of the indispensable moieties of two small molecules (the opioids containing a 4-piperidinyl ring with the FANS indomethacin) might lead to new medicaments potentially useful for the treatment of amyotrophic lateral sclerosis.
Preclinical • Journal
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TNFA (Tumor Necrosis Factor-Alpha)
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riluzole
9ms
Trial completion
9ms
Enrollment open
9ms
Interleukin 3 Inhibits Glutamate-Cytotoxicity in Neuroblastoma Cell Line. (PubMed, Neurochem Res)
Additionally, our findings suggest that Bcl-2 and Bax proteins may be involved in the molecular mechanism triggered by IL-3. Our investigation into IL-3's ability to protect neuronal cells from glutamate-induced damage offers a promising therapeutic avenue with potential clinical implications for several neurological diseases characterized by glutamate neurotoxicity.
Preclinical • Journal • IO biomarker
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BCL2 (B-cell CLL/lymphoma 2) • BAX (BCL2-associated X protein)
10ms
Study of AGN-151586 in Japanese Participants With Moderate to Severe Glabellar Lines (clinicaltrials.gov)
P1, N=24, Active, not recruiting, AbbVie | Recruiting --> Active, not recruiting
Enrollment closed
10ms
New P1 trial
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riluzole
10ms
Olanzapine for the Treatment of Appetite Loss in Amyotrophic Lateral Sclerosis (ALS) (clinicaltrials.gov)
P2/3, N=40, Completed, Charite University, Berlin, Germany | Unknown status --> Completed
Trial completion
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olanzapine • riluzole
12ms
Study of AGN-151586 in Japanese Participants With Moderate to Severe Glabellar Lines (clinicaltrials.gov)
P1, N=24, Recruiting, AbbVie | Not yet recruiting --> Recruiting | Phase classification: P1/2 --> P1
Enrollment open • Phase classification
1year
Oxaloacetate for the Improvement of Cognitive Complaints in Stage 0-IIIA Breast Cancer Survivors (clinicaltrials.gov)
P2, N=24, Recruiting, Jonsson Comprehensive Cancer Center | Trial completion date: Nov 2024 --> Nov 2025 | Trial primary completion date: Nov 2023 --> Nov 2024
Trial completion date • Trial primary completion date
1year
New P1/2 trial
1year
SOLUTION: RiLuzole to Reduce Atrial FIb Study Using Holter Monitoring (clinicaltrials.gov)
P2, N=78, Recruiting, University of Utah | Trial completion date: Oct 2023 --> Oct 2024 | Trial primary completion date: Oct 2023 --> Oct 2024
Trial completion date • Trial primary completion date
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riluzole
1year
Unusual Presentation of Amyotrophic Lateral Sclerosis in a Patient with Recurrent Prostate Cancer: A Case Report (AAPMR 2023)
There was no evidence of myopathy or neuromuscular junction disorder.Setting: Cancer rehabilitation clinicAssessment/ Patient was diagnosed with ALS and started on riluzole... Cancer rehabilitation physicians play a critical role in early recognition and timely diagnosis of disorders like paraneoplastic syndromes and neurodegenerative diseases that can be severely debilitating, difficult to diagnose, and challenging to treat. Patients with a cancer history and concurrent ALS require unique rehabilitation considerations.
Clinical
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CRP (C-reactive protein)
|
riluzole
1year
RILUZOX-01: Effectiveness Assessment of Riluzole in the Prevention of Oxaliplatin-induced Peripheral Neuropathy. (clinicaltrials.gov)
P2, N=80, Active, not recruiting, UNICANCER | Recruiting --> Active, not recruiting | N=210 --> 80 | Trial completion date: Apr 2024 --> Oct 2024 | Trial primary completion date: Sep 2023 --> Sep 2024
Enrollment closed • Enrollment change • Trial completion date • Trial primary completion date
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oxaliplatin • riluzole
1year
Longitudinal Metabolite Changes in Progressive Multiple Sclerosis: A Study of 3 Potential Neuroprotective Treatments. (PubMed, J Magn Reson Imaging)
H-MRS demonstrated altered membrane turnover over 96-weeks in the placebo group. It also distinguished changes in neuro-metabolites related to gliosis and glutaminergic transmission, due to fluoxetine and riluzole, respectively. Data show tNAA is a potential marker for upper limb function.
Journal
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fluoxetine • riluzole
1year
Riluzole Suppresses Growth and Enhances Response to Endocrine Therapy in ER+ Breast Cancer. (PubMed, J Endocr Soc)
We previously reported that the acquisition of tamoxifen resistance in a cellular model of invasive lobular breast cancer is accompanied by the upregulation of GRM mRNA expression and growth inhibition by riluzole. Single-agent riluzole significantly inhibited HCI-013EI patient-derived xenograft growth in vivo, and the combination of riluzole plus fulvestrant significantly reduced proliferation in ex vivo primary breast tumor explant cultures. Riluzole may offer therapeutic benefits in diverse ER+ breast cancers, including lobular breast cancer.
Journal
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ER (Estrogen receptor)
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ER positive • ER mutation • ESR1 mutation
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tamoxifen • fulvestrant • riluzole
1year
Riluzole and Sorafenib Tosylate in Treating Patients With Advanced Solid Tumors or Melanoma (clinicaltrials.gov)
P1, N=35, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2023 --> Sep 2024
Trial completion date • IO biomarker • Metastases
|
BCL2 (B-cell CLL/lymphoma 2) • MCL1 (Myeloid cell leukemia 1) • BCL2L11 (BCL2 Like 11)
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BCL2 expression • MCL1 expression
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sorafenib • riluzole
over1year
Novel therapeutic strategies in glioma targeting glutamatergic neurotransmission. (PubMed, Brain Res)
Other pharmacological strategies that downregulate glutamatergic signalling include riluzole, memantine and anaesthetic agents. Similarly, the significant survival benefit in glioblastoma attributable to alternating electrical fields (Tumour Treating Fields) may be a result of disruption to neurogliomal signalling. Further studies exploring excitatory neurotransmission and glutamatergic signalling and their role in glioma origin, growth and propagation are therefore warranted.
Journal
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riluzole
over1year
Decursinol Angelate Inhibits Glutamate Dehydrogenase 1 Activity and Induces Intrinsic Apoptosis in MDR-CRC Cells. (PubMed, Cancers (Basel))
We developed a multidrug-resistant colorectal cancer cell line, HCT-116, after treatment with cisplatin and 5-fluorouracil. Additionally, GDH1 knockdown on both HCT-116 and HCT-116 corresponded to a decreased expression of γH2AX, catalase, SOD1 and Gpx-1, and an eventual increase in apoptosis markers. In conclusion, inhibition of GDH1 increased ROS production, decreased cell proliferation and increased cell death.
Journal
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ABCB1 (ATP Binding Cassette Subfamily B Member 1) • ERCC1 (Excision repair cross-complementation group 1) • CAT (Catalase)
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cisplatin • 5-fluorouracil
over1year
A phase I trial of riluzole and sorafenib in patients with advanced solid tumors: CTEP #8850. (PubMed, Oncotarget)
Combination therapy with riluzole and sorafenib was safe and tolerable in patients with advanced solid tumors. The partial response in a patient with a RAF1 fusion suggests that further exploration in a genomically selected cohort may be warranted.
P1 data • Journal • Metastases
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KANK4 (KN Motif And Ankyrin Repeat Domains 4) • GRM1 (Glutamate Metabotropic Receptor 1)
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KANK4-RAF1 fusion
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sorafenib • riluzole
almost2years
Depletion of Mannose Receptor-Positive Tumor-associated Macrophages via a Peptide-targeted Star-shaped Polyglutamate Inhibits Breast Cancer Progression in Mice. (PubMed, Cancer Res Commun)
OximUNO comprises a star-shaped polyglutamate (St-PGA) decorated with the CD206-targeting peptide mUNO that carries the chemotherapeutic drug doxorubicin (DOX)...Importantly, our studies also represent a novel design of a peptide-targeted St-PGA as a targeted therapeutic nanoconjugate. A peptide-targeted nanoformulation of DOX exclusively eliminates mannose receptor+ TAMs in breast cancer models, generating response without off-target effects (a drawback of many TAM-depleting agents under clinical study).
Preclinical • Journal
|
CD8 (cluster of differentiation 8) • FOXP3 (Forkhead Box P3) • MRC1 (Mannose Receptor C-Type 1)
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CD8 expression • FOXP3 expression
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doxorubicin hydrochloride
almost2years
BDNF Augmentation Using Riluzole Reverses Doxorubicin-Induced Decline in Cognitive Function and Neurogenesis. (PubMed, Neurotherapeutics)
Importantly, RZ mitigated chemotherapy-induced loss of newly born, immature neurons, dentate neurogenesis, and neuroinflammation. In conclusion, this data provides pre-clinical evidence for a translationally feasible approach to enhance the neuroprotective effects of RZ treatment to prevent CRCI.
Journal
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BDNF (Brain Derived Neurotrophic Factor)
|
doxorubicin hydrochloride • riluzole
almost2years
Synergistic effects of agonists and two-pore-domain potassium channels on secretory responses of human pancreatic duct cells Capan-1. (PubMed, Pflugers Arch)
The H,K-ATPase inhibitor omeprazole reduced carbachol- and riluzole-induced anion transport responses. KCNE1 mRNA and TREK-1, TREK-2, TASK-2, and KCNQ1 protein expression were also shown. This study shows that the Capan-1 model recapitulates key physiological aspects of a bicarbonate-secreting epithelium and constitutes a valuable model for functional studies on human pancreatic duct epithelium.
Journal
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KCNQ1OT1 (KCNQ1 Opposite Strand/Antisense Transcript 1)
|
riluzole
2years
EGFR-phosphorylated GDH1 harmonizes with RSK2 to drive CREB activation and tumor metastasis in EGFR-activated lung cancer. (PubMed, Cell Rep)
Moreover, GDH1, RSK2, and CREB phosphorylation positively correlate with EGFR mutation and activation in lung cancer patient tumors. Our findings reveal a crosstalk between kinase, metabolic, and transcription machinery in metastasis and offer an alternative combinatorial therapeutic strategy to target metastatic cancers with activated EGFRs that are often EGFR therapy resistant.
Journal
|
EGFR (Epidermal growth factor receptor) • CD8 (cluster of differentiation 8) • RPS6KA3 (Ribosomal Protein S6 Kinase A3)
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EGFR mutation
2years
Inhibiting glutamine utilization creates a synthetic lethality for suppression of ATP citrate lyase in KRas-driven cancer cells. (PubMed, PLoS One)
This effect was not observed in MCF7 breast cancer cells that do not have a KRas mutation or in BJ-hTERT human fibroblasts which have no oncogenic mutation. These data reveal a synthetic lethality between inhibition of glutamate oxaloacetate transaminase and ACLY inhibition that is specific for KRas-driven cancer cells and the apparent metabolic reprogramming induced by activating mutations to KRas.
Journal • Synthetic lethality
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KRAS (KRAS proto-oncogene GTPase) • TERT (Telomerase Reverse Transcriptase)
|
KRAS mutation • TERT mutation
over2years
Riluzole and Sorafenib Tosylate in Treating Patients With Advanced Solid Tumors or Melanoma (clinicaltrials.gov)
P1, N=35, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Aug 2022 --> Sep 2023
Trial completion date • IO biomarker
|
BCL2 (B-cell CLL/lymphoma 2) • MCL1 (Myeloid cell leukemia 1) • BCL2L11 (BCL2 Like 11)
|
BCL2 expression • MCL1 expression
|
sorafenib • riluzole
over2years
Significant metabolic alterations in non-small cell lung cancer patients by epidermal growth factor receptor-targeted therapy and PD-1/PD-L1 immunotherapy. (PubMed, Front Pharmacol)
Endogenous metabolism changes occur due to drug action and might be indicative of antitumor therapeutic effect. These findings will provide new clues for identifying the antitumor mechanism of these two treatments from the perspective of metabolism.
Journal
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EGFR (Epidermal growth factor receptor)
over2years
Riluzole regulates pancreatic cancer cell metabolism by suppressing the Wnt-β-catenin pathway. (PubMed, Sci Rep)
Finally, riluzole inhibits pancreatic cancer growth in KPC (Pdx1-Cre, LSL-Trp53, and LSL-Kras) mice. In conclusion, riluzole can inhibit pancreatic cancer growth by regulating glucose and glutamine metabolisms and can be used to treat pancreatic cancer.
Journal • IO biomarker
|
KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • LDHA (Lactate dehydrogenase A) • CCND1 (Cyclin D1) • SLC16A1 (Solute Carrier Family 16 Member 1) • AXIN1 (Axin 1) • PDX1 (Pancreatic And Duodenal Homeobox 1)
|
CCND1 expression • BAX expression
|
riluzole
over2years
LKB1: Can We Target an Hidden Target? Focus on NSCLC. (PubMed, Front Oncol)
Biguanides, by compromising mitochondria and reducing systemic glucose availability, and the glutaminase inhibitor telaglenastat (CB-839), inhibiting glutamate production and reducing carbon intermediates essential for TCA cycle progression, have provided the most interesting results and entered different clinical trials enrolling also LKB1-null NSCLC patients...In conclusion, the absence of the target did not block the development of treatments able to hit LKB1-mutated NSCLCs acting on several fronts. This will give patients a concrete chance to finally benefit from an effective therapy.
Review • Journal • IO biomarker
|
KRAS (KRAS proto-oncogene GTPase) • STK11 (Serine/threonine kinase 11)
|
KRAS mutation
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telaglenastat (CB-839)
over2years
Riluzole and Sorafenib Tosylate in Treating Patients With Advanced Solid Tumors or Melanoma (clinicaltrials.gov)
P1, N=36, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: May 2022 --> Aug 2022 | Trial primary completion date: May 2022 --> Aug 2022
Trial completion date • Trial primary completion date • IO biomarker
|
BCL2 (B-cell CLL/lymphoma 2) • MCL1 (Myeloid cell leukemia 1) • BCL2L11 (BCL2 Like 11)
|
BCL2 expression • MCL1 expression
|
sorafenib • riluzole