2023
DOI: 10.1038/s41598-023-32848-2
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Rational peptide design for inhibition of the KIX–MLL interaction

Abstract: The kinase-inducible domain interacting (KIX) domain is an integral part of the general transcriptional coactivator CREB-binding protein, and has been associated with leukemia, cancer, and various viral diseases. Hence, the KIX domain has attracted considerable attention in drug discovery and development. Here, we rationally designed a KIX inhibitor using a peptide fragment corresponding to the transactivation domain (TAD) of the transcriptional activator, mixed-lineage leukemia protein (MLL). We performed the… Show more

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“…Moreover, in vitro studies demonstrated that the mimic induced effects similar to Celastrol in AML cells, while in vivo experiments showed the prolonged survival of mice engrafted with patient-derived AML cells, mirroring the effects observed with Celastrol [ 21 , 79 ]. Encouraged by these promising results, various laboratories are currently engaged in the development of additional MYB-p300 inhibitory compounds [ 80 , 81 , 82 , 83 ].…”
Section: Myb As a Therapeutic Targetmentioning
confidence: 99%
“…Moreover, in vitro studies demonstrated that the mimic induced effects similar to Celastrol in AML cells, while in vivo experiments showed the prolonged survival of mice engrafted with patient-derived AML cells, mirroring the effects observed with Celastrol [ 21 , 79 ]. Encouraged by these promising results, various laboratories are currently engaged in the development of additional MYB-p300 inhibitory compounds [ 80 , 81 , 82 , 83 ].…”
Section: Myb As a Therapeutic Targetmentioning
confidence: 99%