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Background
IC50: 1 μM (binds to NGF) [1]Ro 08-2750 is an antagonist of nerve growth factor (NGF), which selectively inhibits binding to p75NTR over TRKA147. This selectivity was used to study the functions of p75NTR and TrkA in apoptosis, neuronal differentiation and neurite outgrowth. NGF is a neuropeptide mainly involved in the regulation of growth, proliferation, maintenance, and survival of certain target neurons.In vitro: Ro 08-2750 can bind to the NGF dimer with ~ 1:1 binding ratio. Binding of Ro 08-2750 to NGF induces NGF a concentration-dependent conformational change [1]. Binding with low concentration of Ro 08-2750, NGF can no longer bind to p75NTR anymore, however, binding to TrkA is not impaired. At higher concentrations of Ro 08-2750 more than 5 mM, the NGF/Ro 08-2750 complex can not bind to TrkA as well. In SK-N-MC cells, Ro 08-2750 leads to inhibition of NGF-induced programmed cell death. In PC12 cells, Ro 08-2750 can enhance the signal pathway through TrkA[2].In vivo:. So far, in vivo study has been conducted.Clinical trial: So far, no clinical study has been conducted.
[1] Arkin MR, Wells JA. Small-molecule inhibitors of protein-protein interactions: progressing towards the dream. Nat Rev Drug Discov. 2004 Apr;3(4):301-17.
[2] Niederhauser O, Mangold M, Schubenel R, Kusznir EA, Schmidt D, Hertel C. NGF ligand alters NGF signaling via p75(NTR) and trkA. J Neurosci Res. 2000 Aug 1;61(3):263-72.
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