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J Cancer Metastasis Treat 2019;5:5 I http://dx.doi.org/10.20517/2394-4722.2018.108 Page 27 of 27
Results: Out of the resulting 127 compounds, ritanserin (serotonin antagonist) and compound01
(uncharacterized molecule) were highly specific for DGKα and showed superior potency compared to
R59022 and R59949. In cellular models of XLP-1, both ritanserin and compound01 restored RICD of SAP-
deficient CD8+ without significant toxicity. Moreover, compound01 doesn’t perturb serotonin signalling.
Thus, we executed compound optimization of compound01 that yielded compound02-07 (synthesized
compounds). All those compound01 derivatives are highly specific to DGKα without perturbing serotonin
signalling.
Conclusion: Concluding our work allows us to propose a pharmacological model for the rational design of
DGKα inhibitors and may contribute to the development of innovative therapies for diseases characterized
by RICD resistance such as XLP-1.
