Uses
DBIBB is a non-lipid agonist of LPA2 (lysophosphatidic acid receptor 2), protecting rat intestinal crpyt epithelium-like IEC-6 cells against caspase 3/7 activation and apoptosis.
Biological Activity
dbibb, a butylsulfamoyl benzoic acid analog, is a non-lipid agonist of lpa2 with an ec50 of 0.10 μm. dbibb has no effect at other lpa receptor subtypes [1]. the bioactive phospholipid lysophosphatidic acid (lpa) has been involved in stimulating cell proliferation, migration and survival by acting on its cognate g-protein-coupled receptors. aberrant lpa production, receptor expression and signalling probably contribute to cancer initiation, progression and metastasis [2].
in vitro
dbibb treatment postirradiation significantly (p< 0.01) increased the clonogenic survival of iec-6 cells in the 2-6 gy dose range. dbibb reduced dna fragmentation 4hr after irradiation in a dose dependent manner. dbibb also reduced caspase 3/7 activity and dna fragmentation in lpa2mef treated with adriamycin. in purified cd34+ progenitor cells, dbibb significantly increased the total number of colonies and specifically enhanced the survival of the granulocyte/macrophage lineages [1].
in vivo
using a murine gi-ars mice model of partial-body irradiation (pbi) with shielding of the bone marrow contained in the tibiae, fibulae, and paws, administrations of up to 10 mg/kg of dbibb for 10 days showed no visually observable adverse effects and pathological findings at necropsy, indicating the lack of toxicity. the group that received 10 mg/kg dbibb showed a significant increase in survival. in c57bl/6 mice, dbibb showed a dose-dependent increase in the number of surviving crypts compared with the vehicle control [1].
References
[1] patil r, szabó e, fells j i, et al. combined mitigation of the gastrointestinal and hematopoietic acute radiation syndromes by an lpa 2 receptor-specific nonlipid agonist[j]. chemistry & biology, 2015, 22(2): 206-216.
[2] mills g b, moolenaar w h. the emerging role of lysophosphatidic acid in cancer[j]. nature reviews cancer, 2003, 3(8): 582-591.
