Swappable Binding Sites Reveal a Drug's Target (IMAGE)

Cold Spring Harbor Laboratory

Swappable Binding Sites Reveal a Drug's Target

Caption

(top) This image shows Boehringer Ingelheim generated molecules that inhibit the BRD9 bromodomain. The middle molecule, BI-7273, was selected as the best of the three and was used in experiments with AML cells conducted by CSHL's Vakoc Lab.

(bottom) This is a schematic of the BRD9 protein's domain structure. the protein has multiple subunits, one of which is a bromodomain (BD, colored green) specific to BRD9. The CSHL team swapped this particular domain for the bromodomain of another, similar protein, BRD4. The modified version of BRD9 (with BRD4's bromodomain swapped in) continued to perform an essential function in enabling AML cells to proliferate. This modified protein was "resistant" to the action of BI-7273, proving that the drug's target is the bromodomain native to BRD9.

Credit

Vakoc Lab, CSHL

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