MU1700

This is a new probe for ALK1/ALK2/ALK6 inhibition that has been characterized by the Structural Genomics Consortium. The data that they provide is promising and suggest that MU1700 may be an excellent inhibitor for these targets. However, the probe has not yet been widely adopted and the data reported by SGC has not yet been replicated under external conditions. Caution is suggested until additional publications testing this compound are available.

MU1700 represents an important tool in advancing research in the area of ALK2 biology. This probe has excellent selectivity outside of the ALK family across the kinome, as well as good cellular activity in ALK2 NanoBRET assays. Moreover, the utility of the probe is strongly enhanced by the fact that it has good bioavailability and brain penetration in mice. As a highly drug-like scaffold, this probe therefore has the ability to be useful both for interrogating cellular ALK2 biology and as an in vivo tool where it can engage the target in various tissues of interest. Having a complementary kinase dead analog with similar physicochemical properties as a control is another benefit. Because MU1700 inhibits ALK1 and to a lesser degree ALK6 at a potency level that is likely to be pharmacologically relevant, distinguishing phenotypic effects that are ALK2-specific as opposed to ALK-family without orthogonal biology or other chemical tools may be difficult.