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• W4385268575 abstract "Abstract In our efforts to identify molecules that selectively reduce the expression of BMI1, a stem cell gene, we discovered and characterized the first‐in‐class series of small molecules that modulate the expression of BMI1 protein in cancer cells. Structure–activity and structure–property relationships associated with this series were investigated through medicinal chemistry efforts. These studies revealed important structural features required for achieving anti‐tumor activity and acceptable pharmacokinetic properties within this series. The 4‐CF 3 −Ph at the left‐side of the molecule, a proper placement of the N‐atom on the six‐membered heterocycle in the middle, combined with a properly substituted C(2)‐methyl benzimidazole on the right‐hand side were required to achieve potency, microsomal stability, and exposure upon oral dosing. A compound (PTC‐02) with acceptable pharmacological properties and efficacious in vivo in several tumor animal models was identified." @default.
• W4385268575 created "2023-07-27" @default.
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• W4385268575 date "2023-08-31" @default.
• W4385268575 modified "2023-10-14" @default.
• W4385268575 title "Discovery and SAR studies of potent modulators of BMI‐1 expression." @default.
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• W4385268575 doi "https://doi.org/10.1002/hlca.202300076" @default.
• W4385268575 hasPublicationYear "2023" @default.
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