Zefamenib (BN-104) is an effective selective brain membrane protein inhibitor with oral activity, and it's also a Menin inhibitor, it can block the Menin-MLL interaction and leads to the degradation of Menin protein. Zefamenib is a weak hERG inhibitor, with an IC50 greater than 100 μM. Zefamenib has anti-tumor activity and can be used in cancer research, such as for acute myeloid leukemia [1].
In Vivo, Zefamenib (BN-104) (0-60 mg/kg, oral, twice a day, 21 days) inhibits tumor proliferation in a mouse model[1].
In Vitro, Zefamenib (BN-104) inhibits the proliferation of leukemia cells, with IC50 values of: MV-4-11 AF4 fusion (3.5 nM); MOLM13 AF9 fusion (12 nM); OCI-AML3 NPM1 mutant (11 nM)[1]. Zefamenib (10 μM, 0-24 h) causes degradation of Menin protein in MV-4-11 cells [1].
References:
[1]. Taishan Hu, et al. "Discovery of a novel menin-MLL inhibitor for potential treatment of MLLr leukemias and NPM1c AML." Cancer Research. Vol. 82. No. 12. 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA: AMER ASSOC CANCER RESEARCH, 2022.
In Vivo, Zefamenib (BN-104) (0-60 mg/kg, oral, twice a day, 21 days) inhibits tumor proliferation in a mouse model[1].
In Vitro, Zefamenib (BN-104) inhibits the proliferation of leukemia cells, with IC50 values of: MV-4-11 AF4 fusion (3.5 nM); MOLM13 AF9 fusion (12 nM); OCI-AML3 NPM1 mutant (11 nM)[1]. Zefamenib (10 μM, 0-24 h) causes degradation of Menin protein in MV-4-11 cells [1].
References:
[1]. Taishan Hu, et al. "Discovery of a novel menin-MLL inhibitor for potential treatment of MLLr leukemias and NPM1c AML." Cancer Research. Vol. 82. No. 12. 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA: AMER ASSOC CANCER RESEARCH, 2022.