Ro 08-2750

Description: Ro 08-2750 is a novel, potent, selective, and reversible non-peptide inhibitor of Nerve growth factor (NGF), binding to the NGF dimer with a KD of ca. 1 uM. It inhibits NGF binding to p75NTR selectively over TRKA. Ro 08-2750 is a selective MSI RNA-binding activity inhibitor, with an IC50 of 2.7 uM. NGF has potential effects on matrix turnover activity and influences the catabolic/anabolic balance of IVD cells in an adverse way that may potentiate IVD degeneration. Anti-NGF treatment might be beneficial to ameliorate progressive tissue breakdown in IVD degeneration and may lead to pain relief.

References:

1. Arkin MR, et al. Small-molecule inhibitors of protein-protein interactions: progressing towards the dream. Nat Rev Drug Discov. 2004 Apr; 3(4):301-17.

2. Niederhauser O, et al. NGF ligand alters NGF signaling via p75(NTR) and trkA. J Neurosci Res. 2000 Aug 1; 61(3):263-72.

3. Minuesa G, et al. Small-molecule targeting of MUSASHI RNA-binding activity in acute myeloid leukemia. Nat Commun. 2019 Jun 19; 10(1):2691.

4. Kao TH, Peng YJ, Salter DM, Lee HS. Nerve growth factor increases MMP9 activity in annulus fibrosus cells by upregulating lipocalin 2 expression. Eur Spine J. 2015 Sep; 24(9):1959-68. doi: 10.1007/s00586-014-3675-2. Epub 2014 Nov 21. PubMed PMID: 25412834.