RO 08-2750

Uses

Ro 08-2750 is a TrkA inhibitor and NGF-induced apoptosis inhibitor.

Definition

ChEBI: 7,10-dimethyl-2,4-dioxo-8-benzo[g]pteridinecarboxaldehyde is a flavin.

Biological Activity

Non-peptide inhibitor of NGF that binds the NGF dimer (K D ~ 1 μ M) possibly causing a conformational change. Inhibits binding selectively to p75 NTR at submicromolar concentrations and to both p75 NTR and TrkA at higher concentrations (> 5 μ M). Prevents NGF-induced apoptosis in SK-N-MC cells.

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].

IC 50

1 μm (binds to ngf) [1]

storage

Store at -20°C

References

[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.