HXR9

HXR9 is a cell-permeable peptide and a competitive antagonist of HOX/PBX interaction. HXR9 antagonizes the interaction between HOX and a second transcrip-tion factor (PBX), which binds to HOX proteins in paralogue groups1 to 8. HXR9 selectively decreases cell proliferation and promotes apoptosis in cells with a high level of expression of the HOXA/PBX3 genes, such as MLL-rearranged leukemic cells[1][2][3].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

HXR9 (60μM; 4 hours) blocks the interaction between PBX and HOX[1]. HXR9 (60μM; 2 hours) triggers apoptosis in B16 and primary melanoma cells[1]. HXR9 (60μM; 2 hours) causes specific transcriptional changes[1]. HXR9 (B16 cells) shows antiproliferative activity with an IC50 of 20μM[1]. Western Blot Analysis Cell Line: murine B16melanoma cells Concentration: 60 μM Incubation Time: 4 hours Result: Blocked the binding of HOXD9 to PBX. Apoptosis Analysis Cell Line: B16 cells Concentration: 60 μM Incubation Time: 2 hours Result: A significant proportion of cells were in late phases of apoptosis. RT-PCR Cell Line: B16F10cells Concentration: 60 μM Incubation Time: 2 hours Result: Fos, Jun, Dusp1, and Atf1，were allsignificantly up-regulate.

HXR9 (10 mg/kg; i.v. via the tail vein; twice weekly) blocks tumor growth[1]. HXR9 (Initial dose of 100 mg/kg (subsequent dosing of 10 mg/kg twice weekly);Intraperitoneal; twice weekly for 18 days) blocks A549 tumour growth in vivo[3]. Animal Model: C57black/6 mice (bearing B16 cells) Dosage: 10 mg/kg Administration: I.v. via the tail vein; twice weekly (~30 days) Result: Tumors showed a significant degree of growth retardation. Animal Model: Athymic nude mice (bearing A549 cells) Dosage: Initial dose of 100 mg/kg (subsequent dosing of 10 mg/kg twice weekly) Administration: Intraperitoneal; twice weekly for 18 days Result: The tumours of HXR9-treated mice were considerably smaller than those of the control groups.

[1]. Morgan R, et al. Antagonism of HOX/PBX dimer formation blocks the in vivo proliferation of melanoma. Cancer Res. 2007;67(12):5806-5813.

[2]. Li Z, et al. PBX3 is an important cofactor of HOXA9 in leukemogenesis. Blood. 2013;121(8):1422-1431.

[3]. Plowright L, et al. HOX transcription factors are potential therapeutic targets in non-small-cell lung cancer (targeting HOX genes in lung cancer). Br J Cancer. 2009;100(3):470-475.