AC-0027838 / AlzeCure - LARVOL DELTA

Pharmacological Effects of ACD137, a Potent and Selective Negative Allosteric Modulator of TrkA (IASP 2024) - "The compound was bound in a single conformation at the previously described allosteric site with close to 100% occupancy.Analgesic efficacy was demonstrated in two models including paclitaxel induced CIPN and incisional pain (Brennan model). Oral administration of ACD137 resulted in a significant analgesic effect corresponding to approximately 70% pain reduction, which was similar to 100 mg/kg of Gabapentin or to 30 mg/kg of Tramadol at 3h and 6h in CIPN or Brennan model, respectively... TrkA-NAM's have shown promise in both neuropathic and nociceptive models. Enhanced pain relief is attributed to the inhibition of NGF/TrkA signaling, attenuating peripheral sensitization and inflammation. Identification of selective and potent TrkA-NAM's could potentially avoid some of the side effects observed for anti-NGF antibodies."

Inflammation • Pain • Peripheral Neuropathic Pain • NGF • NTRK2

[VIRTUAL] Negative Allosteric Modulators of TrkA for the Treatment of Pain (IASP 2021) - "Electronic address: franz.hefti@prevailtherapeutics.com.Pharmacology of nerve growth factor and discovery of tanezumab, an anti-nerve growth factor antibody and pain therapeuticPharmacol ResPharmacol Res1042401542019/04/27*Alzheimer's disease*Antibody therapy*Nerve Growth Factor*Neurotrophic factor*Pain*Trk Receptors*Trk antagonist2020Apr1043-66183102650410.1016/j.phrs.2019.04.024NLMeng[1]...In vivo analgesic effects were assessed in two different rat models, the oxaliplatin-induced painful neuropathy model and in the Freund’s complete adjuvant (FCA)-induced arthritis model. A series of potent and selective TrkA-NAMs were identified during a lead generation program... The NGF/TrkA pathway is a well validated and a promising alternative for new analgesics without the side effects and dependency issues observed with opioids. Identification of selective and potent TrkA-NAM’s could potentially avoid some of the side effects observed for anti-NGF antibodies due to a more..."

Addiction (Opioid and Alcohol) • Alzheimer's Disease • Cardiovascular • CNS Disorders • Gastrointestinal Disorder • Immunology • Neuralgia • Osteoarthritis • Pain • Peripheral Neuropathic Pain • Psychiatry • Rheumatology • NGF • NTRK2 • NTRK3