>> comments from the more informed amongst us would be welcome <<
Not commenting directly to p38alpha, as I don't know much about it. However, many intracellular signaling pathways are common to several cell types, and the specificity appears to originate with the receptors which dress the cell. That is, a variety of ligands can trigger the same signal cascade, but a differentiated cell will only express a subset of receptors.
Again, I know little about p38alpha. However, a start from this general perspective -- toxicities due to a lack of specificity -- may help to limit enthusiasm in some situations where it isn't justified.
Is this part of the rush to MAbs? Is the specificity inherent in antagonism at the cell surface -- of inhibiting receptor-ligand interaction -- fundamentally the sound way to go?
Re. the speed needed to complete a phase I study. Fast may be bad. Doses are increased, generally until toxicity is observed, based on tolerance of a preceding, lower dose. A long phase I study may indicate that higher doses were tolerated than anticipated. Just a thought, and, again, I know squat about SCIO. |
