PL37 / Debiopharm, Pharmaleads - LARVOL DELTA

Discovery of a mitochondria-targeted propranolol conjugate PL37 that induces mitophagy for potent anti-hemangioma activity. (PubMed, Bioorg Med Chem) - "In vivo, PL37 significantly suppressed tumor growth and angiogenesis in a hemangioma xenograft model without observable toxicity. These findings establish mitochondrial targeting as a viable strategy to enhance propranolol efficacy and identify PL37 as a promising lead for the development of next-generation anti-hemangioma agents."

Journal • Metabolic Disorders • Oncology

Chinese herbal medicine promotes growth by improving nutrient utilization and rumen microbiota in suckling lambs. (PubMed, Front Microbiol) - "CBM58, GT14, GH89, GH110, GH50, and PL37 showed positive associations with TVFAs. This study demonstrates that dietary supplementation with CCHM during the suckling period improves growth performance, enhances nutrient digestibility, increases rumen fermentation capacity, modulates microbial abundance, and promotes lamb development in Hu sheep."

Journal

Synergistic Effect of Combining Dual Enkephalinase Inhibitor PL37 and Sumatriptan in a Preclinical Model of Migraine (AHS 2025) - "So, we used the rat ISDN model of migraine as sumatriptan have been shown to reduce cephalic MH in this model. After determination of sumatriptan and PL37 ED50, we showed, by isobolographic analysis, that the combination of increasing fractional increments of both drugs doses produced a synergistic effect.So, combining PL37 and sumatriptan may be a useful strategy for migraine management, as an alternative to patients unable to tolerate sumatriptan side effects or those that have not found pain relief in the existing pharmacopeia.Learning Objectives: Upon completion, participant will be able to demonstrate the interest of using combination of analgesics in migraine treatmentAt the end of the training, the participant will be able to demonstrate the interest of targeting enkephalins in the treatment of migraine.Upon completion, participant will be able to demonstrate the interest of using a dual enkephalinase inhibitor in association with sumatriptan"

Preclinical • CNS Disorders • Migraine • Pain • PENK

Antimicrobial Peptides Expressed by the Polyaminoglycoside Nanosystem for Bacterial Peritonitis Management via Inflammation Modulation. (PubMed, Mol Pharm) - "Results indicated that the system significantly improved survival rates, reduced inflammatory responses, and ameliorated histopathological damage, effectively preventing and treating bacterial peritonitis and its complications. In conclusion, the SS-HPT/pLL37 system offers a promising new strategy for the treatment of bacterial peritonitis."

Journal • Fibrosis • Gastroenterology • Hepatology • Immunology • Infectious Disease • Inflammation • Liver Cirrhosis • Septic Shock

Synergistic effect of combining dual enkephalinase inhibitor PL37 and sumatriptan in a preclinical model of migraine. (PubMed, Headache) - "There have been many advances in migraine treatment, but we still need more options that are effective and have few side effects. Sumatriptan is one available drug for acute treatment of migraine, but it does not work for every patient and is not suitable for some people. We tested a new drug called PL37 (that blocks enkephalinases) together with sumatriptan and the combination minimized side effects and allowed lower doses of the drugs for effective migraine treatment in an animal model."

Journal • Preclinical • CNS Disorders • Immunology • Migraine • Pain • PENK

Novel Opioids in the Setting of Acute Postoperative Pain: A Narrative Review. (PubMed, Pharmaceuticals (Basel)) - "Although traditional opioids such as morphine and oxycodone are commonly used in the management of acute postoperative pain, novel opioids may play a role as alternatives that provide potent pain relief while minimizing adverse effects...The more established include oliceridine (biased ligand activity to activate analgesia and downregulate opioid-related adverse events), tapentadol (mu-opioid agonist and norepinephrine reuptake inhibitor), and cebranopadol (mu-opioid agonist with nociceptin opioid peptide activity)-all of which have demonstrated success in the clinical setting when compared to traditional opioids. On the other hand, dinalbuphine sebacate (DNS; semi-synthetic mu partial antagonist and kappa agonist), dual enkephalinase inhibitors (STR-324, PL37, and PL265), and endomorphin-1 analog (CYT-1010) have shown good efficacy in preclinical studies with future plans for clinical trials. Rather than relying solely on mu-opioid receptor agonism to relieve pain and..."

Journal • Review • Anesthesia • CNS Disorders • Depression • Pain • Psychiatry • PENK

Efficacy of dual enkephalinase inhibition in a preclinical migraine model is mediated by activation of peripheral delta opioid receptors. (PubMed, Headache) - "These data demonstrate that inhibiting enkephalinases, and thus protecting enkephalins from degradation, attenuates stress-induced migraine-like behavior via activation of peripheral DOR. Peripheral targeting of endogenous opioid signaling may be an effective therapeutic strategy for migraine."

Journal • Preclinical • CNS Disorders • Immunology • Migraine • Pain • PENK

"OKEA acquires 28% working interest in PL037 (Statfjord Area) from Equinor https://t.co/R2fTLQLDYT" (,@CisionNews)

Dual enkephalinase inhibitor PL37 as a potential novel treatment of migraine: evidence from a rat model. (PubMed, Brain) - "Using behavioral testing and c-Fos immunoreactivity in male rats, we investigated the effects of single (oral or intravenous) and repeated oral administration of PL37 on changes in cutaneous mechanical sensitivity and sensitization of the trigeminocervical complex induced by repeated administration of the nitric oxide donor, isosorbide dinitrate. These data reveal the therapeutic potential of the dual enkephalinase inhibitor PL37 as an acute and prophylactic treatment for migraine. Protecting enkephalins from their degrading enzymes therefore appears as an innovative approach to treat migraine."

Journal • Preclinical • CNS Disorders • Immunology • Migraine • Pain • FOS • PENK

Efficacy of a Dual ENKephalinase Inhibitor in a preclinical stress-induced migraine model (Neuroscience 2021) - "To determine whether the endogenous opioid system could potentially be utilized as a migraine therapeutic approach, we tested the efficacy of an Dual ENKephalinase Inhibitor (DENKI) (PL37) in a preclinical model of migraine...These data demonstrate that inhibiting enkephalinase in the periphery is effective in treating migraine-like behavior via activation of opioid receptors. Peripheral targeting of endogenous opioid signaling may be an effective novel therapeutic strategy for migraine that lack the negative effects commonly associated with centrally-acting opioids.; Grant Support: NIH Grant NS104200"

Preclinical • CNS Disorders • Migraine • Pain • PENK

Insights into ulvan lyase: review of source, biochemical characteristics, structure and catalytic mechanism. (PubMed, Crit Rev Biotechnol) - "Various ulvan lyases have been cloned and characterized from marine bacteria and grouped into five polysaccharide lyase (PL) families, namely: PL24, PL25, PL28, PL37 and PL40 families...Additionally, the structural characteristics and catalytic mechanisms have been introduced in detail. This comprehensive information should be helpful regarding the application of ulvan lyases."

Journal