Yuan Yao
Current Organizations / Institutes
The organizations/institutes from the scholar's latest article
Yuan Yao has a total of 9 co-authors. Here are the top co-authors by number of shared publications:
- Ashraf- Uz- Zaman
Verna and Marrs McLean Department of Biochemistry and Molecular Pharmacology, Baylor College of Medicine, 1 Baylor Plaza, Houston, Texas 77030, United States
1 shared publication - Bala Krishna Moku
Verna and Marrs McLean Department of Biochemistry and Molecular Pharmacology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA
1 shared publication - Chandra Bhushan Mishra
Verna and Marrs McLean Department of Biochemistry and Molecular Pharmacology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA
1 shared publication - Fangrui Wu
Verna and Marrs McLean Department of Biochemistry and Molecular Pharmacology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA
1 shared publication - Jidong Zhao
Verna and Marrs McLean Department of Biochemistry and Molecular Pharmacology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA
1 shared publication - Shenyou Nie
Verna and Marrs McLean Department of Biochemistry and Molecular Pharmacology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA
1 shared publication
Latest Publications
- Open Access
Discovery, Structure–Activity Relationship and In Vitro Anticancer Activity of Small-Molecule Inhibitors of the Protein–Protein Interactions between AF9/ENL and AF4 or DOT1L
Chromosomal translocations involving the mixed lineage leukemia (MLL) gene cause 5–10% acute leukemias with poor clinical outcomes. Protein–protein interactions (PPI) between the most frequent MLL fusion partner proteins AF9/ENL and AF4 or histone methyltransferase DOT1L are drug targets for MLL-rearranged (MLL-r) leukemia. Several benzothiophene-carboxamide compounds were identified as novel inhibitors of these PPIs with IC50 values as low as 1.6 μM. Structure–activity relationship studies of 77 benzothiophene and related indole and benzofuran compounds show that a 4-piperidin-1-ylphenyl or 4-pyrrolidin-1-ylphenyl substituent is essential for the activity. The inhibitors suppressed expression of MLL target genes HoxA9, Meis1 and Myc, and selectively inhibited proliferation of MLL-r and other acute myeloid leukemia cells with EC50 values as low as 4.7 μM. These inhibitors are useful chemical probes for biological studies of AF9/ENL, as well as pharmacological leads for further drug development against MLL-r and other leukemias.
Open AccessDiscovery, Structure–Activity Relationship and In Vitro Anticancer Activity of Small-Molecule Inhibitors of the Protein–Protein Interactions between AF9/ENL and AF4 or DOT1L
Chromosomal translocations involving the mixed lineage leukemia (MLL) gene cause 5–10% acute leukemias with poor clinical outcomes. Protein–protein interactions (PPI) between the most frequent MLL fusion partner proteins AF9/ENL and AF4 or histone methyltransferase DOT1L are drug targets for MLL-rearranged (MLL-r) leukemia. Several benzothiophene-carboxamide compounds were identified as novel inhibitors of these PPIs with IC50 values as low as 1.6 μM. Structure–activity relationship studies of 77 benzothiophene and related indole and benzofuran compounds show that a 4-piperidin-1-ylphenyl or 4-pyrrolidin-1-ylphenyl substituent is essential for the activity. The inhibitors suppressed expression of MLL target genes HoxA9, Meis1 and Myc, and selectively inhibited proliferation of MLL-r and other acute myeloid leukemia cells with EC50 values as low as 4.7 μM. These inhibitors are useful chemical probes for biological studies of AF9/ENL, as well as pharmacological leads for further drug development against MLL-r and other leukemias.