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DRUG CLASS:

FAAH inhibitor

Related drugs:
3ms
Mitigation of cisplatin-induced acute kidney injury through oral administration of FAAH Inhibitor PF-04457845. (PubMed, J Pharmacol Exp Ther)
Significance Statement Oral administration of FAAH inhibitor, can reduce cisplatin-induced DNA damage response, tubular damages, and kidney dysfunction. Inactivation of FAAH could be a potential strategy to prevent cisplatin-induced nephrotoxicity.
Journal
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KIM1 (Kidney injury molecule 1) • CDKN1A (Cyclin-dependent kinase inhibitor 1A)
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cisplatin
5ms
Trial completion
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itraconazole
5ms
Protective effects of fatty acid amide hydrolase inhibition in UVB-activated microglia. (PubMed, Biochim Biophys Acta Mol Cell Biol Lipids)
Pharmacological FAAH inhibition via URB597 counteracted the effects of UVB exposure, decreasing tumor necrosis factor α (TNF-α) and nitric oxide (NO) release and reverting reactive oxidative species (ROS), interleukin-1β (IL-1β), and interleukin-10 (IL-10) levels to the control levels. Our findings support the potential of enhanced fatty acid amide signaling in mitigating UVB-induced cellular damage, paving the way to further exploration of these lipids in light-induced immune responses.
Journal
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TNFA (Tumor Necrosis Factor-Alpha) • IL10 (Interleukin 10) • PTGS2 (Prostaglandin-Endoperoxide Synthase 2) • IL1B (Interleukin 1, beta)
9ms
Phase classification
10ms
Positron Emission Tomography (PET) Imaging Study to Evaluate Enzyme Availability in the Central Nervous System Before and After CC-97489 Administration in Healthy Participants (clinicaltrials.gov)
P1, N=38, Recruiting, Celgene | Trial completion date: Oct 2023 --> Jan 2024 | Trial primary completion date: Oct 2023 --> Jan 2024
Trial completion date • Trial primary completion date
11ms
A Study of JZP150 in Adults With Posttraumatic Stress Disorder (clinicaltrials.gov)
P2, N=282, Completed, Jazz Pharmaceuticals | Active, not recruiting --> Completed
Trial completion
11ms
Trial termination
over1year
Identification of fatty acid amide hydrolase as a metastasis suppressor in breast cancer. (PubMed, Nat Commun)
Here, we report that the lipid-degrading enzyme fatty acid amide hydrolase (FAAH) is a predictor of long-term survival in patients with luminal BC, and that it blocks tumor progression and lung metastasis in cell and mouse models of BC. Together, our findings highlight the potential of FAAH as a biomarker with prognostic value in luminal BC and as a therapeutic target in metastatic disease.
Journal
over1year
Activation of cannabinoid type 1 receptor (CB1) modulates oligodendroglial process branching complexity in rat hippocampal cultures stimulated by olfactory ensheathing glia-conditioned medium. (PubMed, Front Cell Neurosci)
These cultures were also treated with URB597 10-9 M, a FAAH selective inhibitor, or JZL184 10-9 M, a MAGL selective inhibitor, which led to the increase in the concentrations of OEA and 2-AG in the conditioned medium...We also observed no change in the phosphorylation of Akt and ERK 44/42 in any of the conditions used. In conclusion, our data show that the ECS modulates the number and maturation of oligodendrocytes in hippocampal mixed cell cultures.
Preclinical • Journal
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MAPK4 (Mitogen-Activated Protein Kinase 4)
over1year
Genetic Knockout of Fatty Acid Amide Hydrolase (FAAH) Ameliorates Cisplatin-induced Nephropathy in Mice. (PubMed, Mol Pharmacol)
Notably, a selective FAAH inhibitor (PF-04457845) did not interfere with or perturb the antitumor effects of cisplatin in two head and neck squamous cell carcinoma cell lines, HN30 and HN12. Significance Statement Mice lacking the Faah gene are protected from cisplatin-induced inflammation, DNA damage response, tubular damages and kidney dysfunction. Inactivation of FAAH could be a potential strategy to mitigate cisplatin-induced nephrotoxicity.
Preclinical • Journal
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CDKN1A (Cyclin-dependent kinase inhibitor 1A) • IL1B (Interleukin 1, beta) • RELA (RELA Proto-Oncogene)
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cisplatin
almost2years
MicroRNA miR-1275 coordinately regulates AEA/LPA signals via targeting FAAH in lipid metabolism reprogramming of gastric cancer. (PubMed, Cell Death Dis)
Overexpression and knockdown of miR-1275 in vitro could indirectly modulate the above lipid signalling by targeting FAAH, thereby affecting GC progression. Our study indicates that deregulated FAAH is a key lipid signal and the miR-1275/FAAH/AEA/LPA axis can serve as a diagnostic biomarker for GC or as a target for therapy development.
Journal
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MIR127 (MicroRNA 127)
over2years
Knockout of fatty acid amide hydrolase (FAAH) gene attenuates cisplatin-induced nephrotoxicity in mice. (PubMed, FASEB J)
Western blot analysis revealed that in comparison with WT-vehicle mice, WT-cisplatin mice showed significant upregulation of kidney injury molecule-1 (KIM-1), which was remarkably reduced in Faah mice (1.6-fold versus 0.8-fold compared to the WT-vehicle group, p<0.05). These data suggest that inactivation of FAAH prevents nephrotoxicity caused by cisplatin treatment and that targeting FAAH may provide a novel strategy to mitigate cisplatin-induced nephrotoxicity.
Preclinical • Journal
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KIM1 (Kidney injury molecule 1)
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cisplatin
over2years
Multi-Omics Approach Points to the Importance of Oxylipins Metabolism in Early-Stage Breast Cancer. (PubMed, Cancers (Basel))
Results allow us to suppose that oxylipin signatures reflect the organism's level of response to the disease. Our data regarding changes in oxylipins at the system level show that oxylipin profiles can be used to evaluate the early stages of breast cancer.
Journal
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PTGS2 (Prostaglandin-Endoperoxide Synthase 2)
almost3years
Influence of genetic variants of opioid-related genes on opioid-induced adverse effects in patients with lung cancer: A STROBE-compliant observational study. (PubMed, Medicine (Baltimore))
In this study, we compared the incidence of opioid-induced adverse effects between patients with different variants of the genes related to responsiveness to opioid analgesics.Participants were 88 patients with lung cancer who provided general consent for exome sequencing and were treated with morphine or oxycodone at Shizuoka Cancer Center Hospital between April 2014 and August 2018. Incidence rates for 6 adverse effects of opioid therapy (somnolence, nausea, constipation, delirium, urinary retention, and pruritus) were determined and the influence of single nucleotide polymorphisms in coding regions of the opioid μ receptor 1 (OPRM1) (rs1799971), opioid δ receptor 1 (rs2234918), opioid κ receptor 1 (rs1051660), catechol-O-methyltransferase (COMT) (rs4680), dopamine receptor D2 (rs6275), adenosine triphosphate binding cassette B1 (rs1045642), G-protein regulated inward rectifier potassium channel 2 (rs2070995), and fatty acid amide hydrolase (rs324420) genes on those adverse effects were analyzed.Analysis of OPRM1 gene variant status (Asn133Asp A > G) showed that G/G homozygotes were at significantly lower risk of somnolence compared with A allele carriers (0% vs 28.4%; Fisher exact test, P = .005; OR, 0; 95% CI, 0-0.6), and analysis of COMT gene variant status (Val158Met, G > A) showed that G/G homozygotes were at significantly higher risk of somnolence compared with A allele carriers (35.0% vs 10.4%; Fisher exact test, P = .008; OR, 4.5; 95% CI, 1.4-18.1). No relationship between variant status and adverse effects was found for the other genes.These findings demonstrate that OPRM1 and COMT gene variants influence the risk of somnolence as an adverse effect of opioid analgesic therapy.
Clinical • Observational data • Journal • Adverse events • IO biomarker
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DRD2 (Dopamine Receptor D2)
almost3years
Genetic Variants of Fatty Acid Amide Hydrolase Modulate Acute Inflammatory Responses to Colitis in Adult Male Mice. (PubMed, Front Cell Neurosci)
In the amygdala, the mutant A allele led to lower levels of IL-1α, IL-9, macrophage inflammatory protein (MIP)-1β, and MIP-2 independent of colitis-providing additional understanding of how FAAH may serve as a regulator of inflammatory responses in the brain. Together, these data provide insights into how FAAH regulates inflammatory processes in disease.
Preclinical • Journal
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TNFA (Tumor Necrosis Factor-Alpha)
3years
Concentration-dependent effects of chlorpyrifos oxon on peroxisome proliferator-activated receptor signaling in MCF-7 cells. (PubMed, Toxicol In Vitro)
These findings suggest chlorpyrifos may influence lipid metabolism through blocking the degradation of eCBs or eCB-like metabolites and in turn affecting PPAR receptor activation. The results highlight the potential for non-cholinesterase actions of this common insecticide metabolite through disruption of PPAR signaling including effects on lipid metabolism, immune function and inflammation.
Journal
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ABCG2 (ATP Binding Cassette Subfamily G Member 2)
over3years
Selective Fatty Acid Amide Hydrolase Inhibitors as Potential Novel Antiepileptic Agents. (PubMed, ACS Chem Neurosci)
Unwanted cardiac effects were excluded for 3h (Langendorff perfused rat heart). Finally, the new analogue 3h reduced the severity of the pilocarpine-induced status epilepticus as observed for 2a.
Journal
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RELA (RELA Proto-Oncogene)
over3years
PF-3845, a Fatty Acid Amide Hydrolase Inhibitor, Directly Suppresses Osteoclastogenesis through ERK and NF-κB Pathways In Vitro and Alveolar Bone Loss In Vivo. (PubMed, Int J Mol Sci)
Furthermore, the administration of PF-3845 decreased the number of osteoclasts and the amount of alveolar bone destruction caused by ligature placement in experimental periodontitis in vivo. The present study provides evidence that PF-3845 is able to suppress osteoclastogenesis and prevent alveolar bone loss, and may give new insights into its role as a treatment for osteoclast-related diseases.
Preclinical • Journal
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NFATC1 (Nuclear Factor Of Activated T Cells 1)
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PF-3845
almost4years
Effects of orthotopic implantation of rat prostate tumour cells upon components of the N-acylethanolamine and monoacylglycerol signalling systems: an mRNA study. (PubMed, Sci Rep)
Treatment of the AT1 cells with interleukin-6, a cytokine known to be involved in the pathogenesis of prostate cancer, did not affect the expression of the components of the NAE/MAG system studied. It is thus concluded that in the model system studied, the tumours show different expressions of mRNA coding for key the components of the NAE/MAG system compared to the host tissue, but that these changes are not accompanied by alterations in the non-malignant tissue.
Preclinical • Journal
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IL6 (Interleukin 6)
4years
Cannabinoid receptor subtype influence on neuritogenesis in human SH-SY5Y cells. (PubMed, Mol Cell Neurosci)
Endocannabinoid ligands 2-arachidonoylglycerol (2-AG) and anandamide were quantitated in SH-SY5Y cells, and diacylglycerol lipase inhibitor tetrahydrolipstatin decreased 2-AG abundance by 90% but did not alter anandamide abundance...CB receptor expression increased GAP43 and ST8SIA2 mRNA and decreased ITGA1 mRNA, whereas CB receptor expression increased NCAM and SYT mRNA. We propose that basal endogenous production of 2-AG provides autocrine stimulation of CB receptor signaling through Gi/o, Gβγ, and β-arrestin mechanisms to promote neuritogenesis, and rho kinase influences process extension.
Journal
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NCAM1 (Neural cell adhesion molecule 1)
over4years
N-Methyladenosine Modification of Fatty Acid Amide Hydrolase Messenger RNA in Circular RNA STAG1-Regulated Astrocyte Dysfunction and Depressive-like Behaviors. (PubMed, Biol Psychiatry)
Our findings dissect the functional link between circSTAG1 and mA methylation in the context of MDD, providing evidence that circSTAG1 may be a novel therapeutic target for MDD.
Journal
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GFAP (Glial Fibrillary Acidic Protein)
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ALK translocation