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This presentation highlights the structure-based design and synthesis of novel iminopyrimidinone compounds, leading to the discovery of potent aspartyl protease inhibitors targeting key diseases: Alzheimer’s, hypertension, malaria, and discovery of novel ELN-YEATS inhibitor for leukemia.
Alzheimer’s Disease (BACE-1): Targeting β-secretase (BACE-1), an enzyme critical for amyloid-beta (Aβ) peptide production, our compounds effectively disrupt the formation of Aβ plaques linked to neurodegeneration.
Hypertension (Renin): Optimization of the pharmacophore produced a selective, orally active renin inhibitor with favorable pharmacokinetic properties, addressing longstanding challenges in blood pressure management.
Malaria (Plasmepsins): Dual inhibitors of PMIX and PMX were developed, demonstrating efficacy across multiple Plasmodium life stages and advancing to human Phase 1 trials as promising candidates for malaria treatment and prevention.
Leukemia (ENL-YEATS): The discovery of TDI-11055, a potent ENL-YEATS domain inhibitor, underscores a novel epigenetic approach to treating acute myeloid leukemia (AML). This compound, licensed to Bridge Medicines, represents a breakthrough in disrupting oncogenic transcription in AML.
These findings showcase the power of structure-based design in delivering innovative therapeutic solutions for some of the most challenging diseases. |