product of a high throughput drug-screening program and must have satisfied multiple criteria for selection as lead compound, it is expected to exhibit good pharmacokinetic properties. XL413 was shown to be a highly potent inhibitor with IC50 values in single digit nanomolar range. Moreover, it was highly selective for DDK over a panel of 100 kinases. With such properties, the poor growth suppressive properties of XL413 among so many cell lines cannot be easily explained. We also performed analyses with XL413 purchased from a separate commercial supplier, MedKoo Inc, however this compound had DPH-153893 chemical information identical cellular potency profiles as the compound synthesized by CGeneTech . Both HCC1954 and Colo-205 cells were cultured in RPMI-1640 media supplemented with 10 fetal bovine serum. Since, the inhibitor functions well in Colo-205 cells, precipitation of XL413 in media cannot be the reason for its inactivity. Possible reasons for its compromised activity on cell lines include poor permeability through the cell membrane, degradation by metabolic enzymes, modification to an inactive form, or higher sensitivity to efflux transporters. In principle, these possible deficits could be identified and then circumvented through synthesis of YYA-021 additional chemical derivatives. Our analysis of XL413 highlights a need for additional biologically active DDK inhibitors. Most ATP competitive inhibitors were optimized by structure activity relationship studies on existing scaffolds of chemical inhibitors. PHA-767491 and XL413 were optimized from scaffolds for MK2 and PIM inhibitors, respectively . To identify further chemical scaffolds for development of DDK inhibitors, we tested if any well-known kinase inhibitors cross-reacted with human DDK. This is a possibility since ATP-competitive kinase inhibitors bind within a related ATP-binding pocket. Using a TSA screen, we identified 12 small molecules that significantly shifted the thermal stability of DDK. Several of these functioned comparatively to PHA-767491 in the assay: the Rho kinase inhibitor , the PKR inhibitor, and the Chk1 inhibitor . These compounds fall into different structural classes indicating that significant chemical space i