JP4-039 is an electron-/reactive oxygen species (ROS)-scavenging GS-nitroxide composed of 4-amino-TEMPO and a truncated gramicidin S (GS) mitochrondria-targeting sequence. JP4-039 is a superior irradiation mitigator than XJB-5-131 (33% vs. 20% mice survial rate on day 35 with respective compound; 23.6 μmol/kg iv. 24 hr post 9.5 Gy whole body irradiation), while displaying weaker anti-ferroptotic potency (EC50 = 3.58 μM/1.27 μM against 10 μM erastin-/2 μM RSL3-induced HT-1080 ferroptosis vs. 114 nM/68 nM with XJB-5-131) due to lower lipophilicity & mitochondria enrichment. Typical dosing range: 40 nM-10 μM in cultures and 10-20 mg/kg in mice (im., ip., iv.) in vivo.
Mitochondrial-targeted reactive oxygen species (ROS)-scavenging gramicidin S (GS)-nitroxide with in vitro and in vivo efficacy against irradiation-induced damage.
In vivo (Athens, Greece), 24(4), 377-385 (2010-07-30)
We studied radioprotection and mitigation by mitochondrial-targeted Tempol (GS-nitroxide, JP4-039), in a mouse injury/irradiation model of combined injury (fracture/irradiation). Right hind legs of control C57BL/6NHsd female mice, mice pretreated with MnSOD-PL, JP4-039, or with amifostine were irradiated with single and
The acute lethality of total-body irradiation (TBI) involves damage to multiple organs, including bone marrow and intestine. Ionizing radiation mitigators that are effective when delivered 24 h or later after TBI include the anti-apoptotic drug, JP4-039 and the anti-necroptotic drug
In vivo (Athens, Greece), 23(5), 717-726 (2009-09-26)
It was unknown if a mitochondria-targeted nitroxide (JP4-039) could augment potentially lethal damage repair (PLDR) of cells in quiescence. We evaluated 32D cl 3 murine hematopoietic progenitor cells which were irradiated and then either centrifuged to pellets (to simulate PLDR
Discovering compounds and mechanisms for inhibiting ferroptosis, a form of regulated, nonapoptotic cell death, has been of great interest in recent years. In this study, we demonstrate the ability of XJB-5-131, JP4-039, and other nitroxide-based lipid peroxidation mitigators to prevent
In vivo (Athens, Greece), 24(6), 811-819 (2010-12-18)
this study evaluated esophageal radioprotection by the Gramicidin S (GS) derived-nitroxide, JP4-039, a mitochondrial targeting peptide-isostere covalently-linked to 4-amino-Tempo, delivered in a novel swallowed oil-based (F15) formulation. C57BL/6HNsd female mice received intraesophageal F15 formulation containing JP4-039 (4 mg/ml in 100
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