GW842166 / GSK - LARVOL DELTA

The expression signature, prognostic significance and immune cell infiltration of the OAS gene family in gastric cancer. (PubMed, Sci Rep) - "Drug prediction and molecular docking identified chlorendic acid, idarubicin, PHA-848,125, and tosedostat as potential activators of the OAS family due to their strong binding affinity. Conversely, GW842166, NSC 23,766, and metolazone showed high binding affinity for OASL and may inhibit its expression. In summary, The OAS gene family, associated with poor prognosis in gastric cancer, promotes tumour progression and represents a promising therapeutic target."

Journal • Gastric Cancer • Oncology • Solid Tumor • ACTA2 • IL17A • OASL • SFRP4

A mouse model of chronic primary pain that integrates clinically relevant genetic vulnerability, stress, and minor injury. (PubMed, Sci Transl Med) - "Last, we assessed the predictive validity of the model for analgesic screening and found that it successfully predicted the lack of efficacy of minocycline and the CB2 agonist GW842166X, which were effective in spared nerve injury and complete Freund's adjuvant models, respectively, but failed in clinical trials. Yet, pain in the CPPC model was alleviated by the beta-3 adrenergic antagonist SR59230A. Thus, the CPPC mouse model reliably recapitulates clinically and biologically relevant features of CPPCs and may be implemented to test underlying mechanisms and find new therapeutics."

Journal • Preclinical • Pain • Psychiatry • COMT • IL17A • IL6

A novel mouse model of chronic primary pain conditions that integrates COMT genotype and environmental stress/injury (Neuroscience 2023) - "Finally, we assessed the predictive validity of the CPPC model for analgesic screening and found that it successfully predicted the lack of efficacy of minocycline and the CB2 agonist GW842166X, which were shown to be effective in the spared nerve injury (SNI) and complete Freund's adjuvant (CFA) models, respectively, but failed clinical trials. Thus, our novel mouse model reliably recapitulates clinically- and biologically-relevant features of CPPCs and can be further implemented to test underlying mechanisms and discover new therapeutics. Funding: NIH/NINDS R01 NS109541 and R61/R33 NS123753 to A Nackley."

Preclinical • CNS Disorders • Pain • Psychiatry • COMT • IL17A • IL6 • KIM1

Synaptamide Phosphonate-GAO-3-02-potentiates GABAergic transmission in the rat lithium-pilocarpine model of temporal lobe epilepsy via activation of CB2 receptor (Neuroscience 2023) - "However, bath perfusion of GW842166X, a potent and selective CB2 receptor agonist, which is undergoing clinical development, failed to significantly increase the current amplitude of eIPSCs. The present study suggests that GAO-3-02 enhances GABAergic transmission onto CA1 pyramidal neurons through activating CB2 receptor. Our results may provide a cellular and molecular mechanism that helps explain the anti-seizure effects of GAO-3-02 in the rat lithium-pilocarpine model of temporal lobe epilepsy."

Preclinical • CNS Disorders • Epilepsy

Specific Activation of CB2R Ameliorates Psoriasis-Like Skin Lesions by Inhibiting Inflammation and Oxidative Stress. (PubMed, Inflammation) - "In this study, imiquimod (IMQ)-induced experimental psoriasis mice and tumor necrosis factor-α (TNF-α)-activated keratinocytes (HaCaT) were used to examine the effect of CB2R activation on psoriasis-like lesions and the mechanism in vivo and in vitro. Our results demonstrated that activation of CB2R by the specific agonist GW842166X (GW) significantly ameliorated IMQ-induced psoriasiform skin lesions in mice by reducing epidermal thickness and decreasing plaque thickness...Further studies suggested that the Kelch-like ECH-associated protein 1/nuclear factor erythroid-2-related factor (Keap1/Nrf2) signaling pathway might be involved. Our findings reveal that selective activation of CB2R may serve as a new strategy for the treatment of psoriasis."

Journal • Dermatology • Immunology • Inflammation • Oncology • Psoriasis • TNFA

GW842166X Alleviates Osteoarthritis by Repressing LPS-mediated Chondrocyte Catabolism in Mice. (PubMed, Curr Med Sci) - "GW842166X impeded the LPS-mediated catabolism in mouse chondrocytes, thereby inhibiting the progression of osteoarthritis."

Journal • Preclinical • Immunology • Osteoarthritis • Pain • Rheumatology • IL10 • IL6 • MMP13 • NFKBIA • RELA • TGFB1 • TNFA

CB2 Agonist GW842166x Protected against 6-OHDA-Induced Anxiogenic- and Depressive-Related Behaviors in Mice. (PubMed, Biomedicines) - "GW842166x treatments ameliorated 6-OHDA-induced anxiogenic- and depressive-like behaviors, but the effects were blocked by CB2 antagonism, suggesting a CB2-dependent mechanism. These results suggest that the CB2 agonist GW842166x not only reduces 6-OHDA-induced motor function deficits but also anxiogenic- and depressive-like behaviors in 6-OHDA mouse models of PD."

Journal • Preclinical • CNS Disorders • Depression • Mental Retardation • Mood Disorders • Movement Disorders • Parkinson's Disease • Psychiatry

Cannabis and orofacial pain: a systematic review. (PubMed, Br J Oral Maxillofac Surg) - "Conversely, two orally-administered synthetic cannabinoid receptor agonists (AZD1940 and GW842166) failed to demonstrate significant analgesic effects following surgical third molar removal. Further research is warranted to explore and substantiate the therapeutic role of CBPMs in the context of orofacial pain and inflammation. As evidence supporting their use expands, healthcare professionals should pay close attention to outcomes and changes to legislation that may impact and potentially benefit their patients."

Journal • Review • Immunology • Inflammation • Musculoskeletal Pain • Neuralgia • Pain

The Neuroprotective Effects of the CB2 Agonist GW842166x in the 6-OHDA Mouse Model of Parkinson's Disease. (PubMed, Cells) - "Here, we report that the selective CB2 agonist GW842166x exerted protective effects against the 6-hydroxydopamine (6-OHDA)-induced loss of dopamine neurons and its associated motor function deficits in mice, as shown by an improvement in balance beam walking, pole, grip strength, rotarod, and amphetamine-induced rotation tests. We found that the bath application of GW842166x led to a decrease in action potential firing, likely due to a decrease in hyperpolarization-activated currents (I) and a shift of the half-activation potential (V) of I to a more hyperpolarized level. Taken together, the CB2 agonist GW842166x may reduce the vulnerability of dopamine neurons to 6-OHDA by decreasing the action potential firing of these neurons and the associated calcium load."

Journal • Preclinical • Cardiovascular • CNS Disorders • Movement Disorders • Parkinson's Disease • Vascular Neurology

Relative Bioavailability Study on a Single Dose of GW842166X in Healthy Male and Female Subjects. (clinicaltrials.gov) - P1; N=0; Withdrawn; Sponsor: GlaxoSmithKline; N=36 -> 0 ; Terminated -> Withdrawn

Enrollment change • Trial withdrawal • Biosimilar • Immunology • Pain

Dose Response and Efficacy of GW842166 in Pain (clinicaltrials.gov) - P1; N=0; Withdrawn; Sponsor: GlaxoSmithKline; Terminated -> Withdrawn

Trial withdrawal • Biosimilar • Pain