The global effort to combat malaria has seen significant progress, yet challenges persist, particularly with emerging resistance to current frontline antimalarials and insecticides. 1 As a result, novel chemotherapeutic agents are urgently needed to address the stagnation in infection reduction and even the resurgence observed in some regions. We targeted the malaria parasite protein kinase PfCLK3, essential for blood stage parasite survival, as a potential avenue for therapeutic intervention. Our approach involved the identification and validation of PfCLK3 as a promising target for malaria treatment, culminating in the discovery of TCMDC-135051 (1) as a selective inhibitor. In this study, we leveraged this tool compound, and embarked on a drug development program aimed at generating a pre-clinical candidate with curative, transmissionblocking, and prophylactic properties across Plasmodium species.