Description
BGP-15 (66611-37-8) is a cellular protectant operating by several mechanisms. It is an insulin sensitizer1, HSP72 activator2, PARP inhibitor and ROS and lipid peroxidation reducer3. It protects mitochondria in acetaminophen-induced liver injury4 as well as LPS-induced destabilization5 and activates mitochondrial fusion6. Displays protective effects in heart failure7 and traumatic brain injury8 in animal models.
Uses
BGP 15 is a calcipotriene-based vitamin D3 analog that inhibits poly(ADP-ribose) polymerasesis (PARP), a class of enzymes that regulate DNA repair and apoptosis (1). BGP 15 is also a cardioprotective agent (2). Also, BPG 15 improves mitochondrial function, protects neurons from dying in vitro and in vivo, and promotes cardiac innervation in vivo.
in vitro
previous study showed that bgp-15 at 200 μm could prevent the imatinib-induced oxidative damages, attenuate the depletion of high-energy phosphates, alter the signaling effect of imatinib by preventing p38 map kinase and jnk activation, and also induce the akt and gsk-3β phosphorylation [1].
in vivo
in-vivo study indicated that bgp-15 improved cardiac function and reduced arrhythmic episodes in two hf and af mouse models. in these models, bgp-15 was associated with increased phosphorylation of igf1r. moreover, cardiac-specific igf1r transgenic overexpression in mice recapitulated the protection caused by bgp-15. the authors further demonstrated that bgp-15 with igf1r could provide protection independent of phosphoinositide 3-kinase-akt and heat-shock protein 70 [2].
References
[1] ÁGOTA PETŐ. Pharmacological Overview of the BGP-15 Chemical Agent as a New Drug Candidate for the Treatment of Symptoms of Metabolic Syndrome.[J]. Molecules, 2020, 25 2. DOI:
10.3390/molecules25020429[2] DARREN C HENSTRIDGE. Activating HSP72 in rodent skeletal muscle increases mitochondrial number and oxidative capacity and decreases insulin resistance.[J]. ACS Applied Nano Materials, 2014: 1881-1894. DOI:
10.2337/db13-0967[3] ESZTER SZABADOS . BGP-15, a nicotinic amidoxime derivate protecting heart from ischemia reperfusion injury through modulation of poly(ADP-ribose) polymerase[J]. Biochemical pharmacology, 2000, 59 8: Pages 937-945. DOI:
10.1016/s0006-2952(99)00418-9[4] FARKAS SARNYAI. BGP-15 Protects Mitochondria in Acute, Acetaminophen Overdose Induced Liver Injury[J]. Pathology & Oncology Research, 2019, 24 1: 1797-1803. DOI:
10.1007/s12253-019-00721-1[5] KATALIN SUMEGI. BGP-15 Protects against Oxidative Stress- or Lipopolysaccharide-Induced Mitochondrial Destabilization and Reduces Mitochondrial Production of Reactive Oxygen Species[J]. PLoS ONE, 2017. DOI:
10.1371/journal.pone.0169372[6] ALIZ SZABO . Activation of mitochondrial fusion provides a new treatment for mitochondria-related diseases[J]. Biochemical pharmacology, 2018, 150: Pages 86-96. DOI:
10.1016/j.bcp.2018.01.038[7] GEETA SAPRA. The small-molecule BGP-15 protects against heart failure and atrial fibrillation in mice.[J]. Nature Communications, 2014: 5705. DOI:
10.1038/ncomms6705[8] BINNUR EROGLU. Therapeutic inducers of the HSP70/HSP110 protect mice against traumatic brain injury[J]. Journal of Neurochemistry, 2014, 130 5: 626-641. DOI:
10.1111/jnc.12781
