Repositioning Candidate Details
| Candidate ID: | R1367 |
| Source ID: | DB11333 |
| Source Type: | approved; investigational |
| Compound Type: | small molecule |
| Compound Name: | Poloxamer 188 |
| Synonyms: | Pluronic F68; Poloxamer-188; Vepoloxamer |
| Molecular Formula: | -- |
| SMILES: | -- |
| DrugBank Description: | Poloxamer 188 (P188) is a nonionic block linear copolymer that exhibits rheologic, anti-thrombotic, anti-inflammatory, and cytoprotective activities in various tissue injury models . Composed of two hydrophilic side-chains attached to a hydrophobic center core , its average molecular weight is 8400 Daltons. P188 was originally approved by the FDA in the 1960s as a therapeutic agent to reduce viscosity in the blood before transfusions, however it is no longer available in any approved products . Due to its sufactant properties, P188 may also be found in over-the-counter (OTC) products such as toothpaste, laxatives and mouthwash, and used in various cosmetic, industrial and pharmaceutical applications. There is an evidence of P188 increasing the structural stability and resealing of the plasma membrane via direct incorporation into the phospholipid bilayer . The ability of P188 in attenuating membrane damage and cell injury has been demonstrated in a variety of _in vivo_ and _in vitro_ models . The use of P188 as a potential treatment in different pathological conditions, such as chronic microvascular diseases and skeletal muscle deficiencies, is under investigation . |
| CAS Number: | 691397-13-4 |
| Molecular Weight: | |
| DrugBank Indication: | Indicated to reduce viscosity in the blood before transfusions. |
| DrugBank Pharmacology: | Poloxamer 188 (P188) exerts a protective action against oxidative stress and inflammation in tissue injury in various experimental models. In the rat model of excitotoxic injury, immediate intrathecal administration of P188 reduced neuronal loss, indicated by smaller spherical excitotoxic lesions . In a murine hind-limb model, P188 mediated a protective action against ischemia-reperfusion injury as indicated by decreased myocyte injury, preserved tissue adenosine 5'-triphosphate levels, and improved survival rates, suggesting that P188 can seal defects in cell membranes and attenuate damage induced by reactive oxygen species . P188 was shown to elicit protective effects against excitotoxic injury, and trauma-induced necrotic and apoptotic cell death in cultured neurons . In the mouse stroke models, P188 exerted a neuroprotective effect in brain ischemia-reperfusion induced acute injury by significantly reducing infarct volume and water content in brain edema and ameliorating the neurological symptoms 24 h after ischemia or reperfusion injury . P188 also significantly inhibited inflammatory, coagulation, and apoptotic responses resulting from superior mesenteric artery occlusion . In the experimental model of striatum injury in rats, P188 was shown to reduce excitotoxicity-induced tissue loss and macrophage infiltrate . |
| DrugBank MoA: | P188 seals stable defects in cell membranes induced by skeletal muscle cell membranes rupture induced by ischemia-reperfusion injury, electroporation, irradiation, and heat damage . The full mechanism of action of P188 in inducing cytoprotective effects is not clear; however, based on _in vitro_ experiments and the structural similarity to plasmalemma, P188 may be directly incorporated into the phospholipid bilayer to attenuate the extent of tissue injury . Its high surface activity facilitates P188 to be inserted into lipid monolayers . P188 is proposed to exert localized actions by only interacting with damaged and compromised bilayers where the local lipid packing density is reduced . In addition to the direct interaction with the membrane, P188 was shown to inhibit MMP-9 protein levels and activity, as well as the NF-κB signal pathway, in the model of acute cerebral ischemia, which is associated with increased BBB permeability leading to cerebral edema and increased penetration . MMP-9 is a key factor in extracellular matrix (ECM) degradation and BBB disruption. |
| Targets: | -- |
| Inclusion Criteria: | Therapeutic strategy associated |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs | |
|---|---|---|---|---|---|
| S04 | Anti-oxidative stress | oxidative stress | α-tocopherol: antioxidant | Vitamin E | Details |
| S05 | Anti-inflammatory | inflammatory | Bile acid; TNF-a inhibitor; Dual PPAR-α and -δ agonists; Toll-Like Receptor; (TLR)-4 antagonist; Caspase inhibitor; ASK-1 inhibitor | Ursodeoxycholic Acid; Pentoxifylline; Elafibranor; JKB-121; Emricasan; Selonsertib; | Details |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name |
|---|
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I16 | 6713 | Cerebrovascular disease | An vascular disease that is characterized by dysfunction of the blood vessels supplying the brain. http://en.wikipedia.org/wiki/Cerebrovascular_disease, http://www.ncbi.nlm.nih.gov/books/NBK378/ | disease of anatomical entity/ cardiovascular system disease/ vascular disease/cerebrovascular disease | Details |