935481-06-4
Chemical Structure
PL37
Synonym(s): Debio-0827
- CAS. Nr.: 935481-06-4
- Formula:C22H34N2O6S3
- Molecular Weight:518.71
IUPAC Name: 1-((ethoxycarbonyl)oxy)ethyl ((S)-3-(((S)-2-amino-4-(methylthio)butyl)disulfanyl)-2-benzylpropanoyl)glycinate
InChIKey: BJCNUZJDFWFVBY-VITQDTLGSA-N
SMILES: CSCC[C@H](N)CSSC[C@@H](CC1=CC=CC=C1)C(NCC(OC(C)OC(OCC)=O)=O)=O
Biological Activity: PL37 (Debio-0827) is an orally active, blood-brain barrier permeable dual enkephalinase inhibitor. PL37 inhibits aminopeptidase N, neprilysin, and metalloproteases, thereby blocking the degradation of endogenous enkephalins, elevating enkephalin levels, and activating peripheral μ- and δ-opioid receptors. PL37 induces mitochondrial dysfunction, mitophagy, and apoptosis, inhibits endothelial cell proliferation, migration, invasion, and tube formation, and suppresses hemangioma tumor growth and angiogenesis. PL37 can be used in research related to peripheral neuropathic pain, osteosarcoma-induced hyperalgesia, painful diabetic neuropathy, migraine, bone cancer pain, neuroinflammatory pain, and infantile hemangioma[1][2][3][4][5][6][7][8][9][10].
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PL37 | PL37 (Debio-0827) is an orally active, blood-brain barrier permeable dual enkephalinase inhibitor. PL37 inhibits aminopeptidase N, neprilysin, and metalloproteases, thereby blocking the degradation of endogenous enkephalins, elevating enkephalin levels, and activating peripheral μ- and δ-opioid receptors. PL37 induces mitochondrial dysfunction, mitophagy, and apoptosis, inhibits endothelial cell proliferation, migration, invasion, and tube formation, and suppresses hemangioma tumor growth and angiogenesis. PL37 can be used in research related to peripheral neuropathic pain, osteosarcoma-induced hyperalgesia, painful diabetic neuropathy, migraine, bone cancer pain, neuroinflammatory pain, and infantile hemangioma. | |||||||||||||||||||||
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References
- [1]. Thibault K, et al. Antinociceptive and anti-allodynic effects of oral PL37, a complete inhibitor of enkephalin-catabolizing enzymes, in a rat model of peripheral neuropathic pain induced by vincristine. European journal of pharmacology. 2008 Dec 14;600(1-3):71-7. [Content Brief]
- [2]. Menéndez L, et al. Inhibition of osteosarcoma-induced thermal hyperalgesia in mice by the orally active dual enkephalinase inhibitor PL37. Potentiation by gabapentin. European journal of pharmacology. 2008 Oct 31;596(1-3):50-5. [Content Brief]
- [3]. Tesfaye S, et al. PL37: a new hope in the treatment of painful diabetic neuropathy?. Pain management. 2016 Apr;6(2):129-32. [Content Brief]
- [4]. Descheemaeker A, et al. Dual enkephalinase inhibitor PL37 as a potential novel treatment of migraine: evidence from a rat model. Brain : a journal of neurology. 2022 Aug 27;145(8):2664-2670. [Content Brief]
- [5]. Rossignol J, et al. Synergistic effect of combining dual enkephalinase inhibitor PL37 and sumatriptan in a preclinical model of migraine. Headache. 2024 Mar;64(3):243-252. [Content Brief]
- [6]. Ashina M. Targeting enkephalins and pituitary adenylate cyclase-activating polypeptide (PACAP) in migraine. Brain. 2022 Aug 27;145(8):2619-2620. [Content Brief]
- [7]. Poras H, et al. Protection of endogenous enkephalins by PL37, a dual NEP/APN inhibitor induces potent analgesic responses p.o. in neuropathic pain [poster]. XXth International Symposium on Medicinal Chemistry (EFMC-ISMC 2008); 2008 Aug 31–Sep 4; Vienna, Austria.
- [8]. González-Rodríguez S, et al. Involvement of enkephalins in the inhibition of osteosarcoma-induced thermal hyperalgesia evoked by the blockade of peripheral P2X3 receptors. Neuroscience letters. 2009 Nov 20;465(3):285-9. [Content Brief]
- [9]. Zhang M, et al. Discovery of a mitochondria-targeted propranolol conjugate PL37 that induces mitophagy for potent anti-hemangioma activity. Bioorganic & medicinal chemistry. 2026 Oct;141:118750. [Content Brief]
- [10]. Mei HR, et al. Efficacy of dual enkephalinase inhibition in a preclinical migraine model is mediated by activation of peripheral delta opioid receptors. Headache. 2023 May;63(5):621-633. [Content Brief]
