AI-10-49

Research use only, not for human use.

AI-10-49 is a selective inhibitor of the binding of CBFβ-SMMHC to RUNX1 with IC50 of 260 nM.

AI-10-49 is an inhibitor that binds the transcription factor fusion CBFβ-SMMHC. AI-10-49, that selectively binds to CBFβ-SMMHC and disrupts its binding to RUNX1. AI-10-49 restores RUNX1 transcriptional activity, displays favorable pharmacokinetics, and delays leukemia progression in mice. Treatment of primary inv(16) AML patient blasts with AI-10-49 triggers selective cell death. These data suggest that direct inhibition of the oncogenic CBFβ-SMMHC fusion protein may be an effective therapeutic approach for inv(16) AML, and they provide support for transcription factor targeted therapy in other cancers.(In Vitro):AI-10-49 inhibits the binding of CBFβ-SMMHCto theRUNX1 Runt domain with IC50 value of 0.26 μM.AI-10-49 (1 μM; 3, 6, 12 hours) has selectivity for inhibiting CBFβ-SMMHC binding to RUNX1.(In Vivo):AI-10-49 (200 mg/kg; per day) delays leukemia progression in mice.

Western Blot Analysis Cell Line:ME-1 cells Concentration:1 μM Incubation Time:3, 6 hours Result:Effectively dissociated RUNX1 from CBFβ-SMMHC.RT-PCRCell Line:ME-1 and U937 cells Concentration:1 μM Incubation Time:6, 12 hours Result:Increased expression of RUNX3, CSF1R, and CEBPA.

Animal Model:Mice (Cbfb+/MYH11:Ras+/G12D leukemic cells)Dosage:200 mg/kg Administration:per day Result:Reduced leukemia expansion in vivo and survived significantly long.

AI-10-49 | AI 10-49 | AI10-49

Tyrosine Kinase

Ephrin Receptor

CBFβ-SMMHC

Cancer

——

1256094-72-0

660.52

C30H22F6N6O5

>98% (HPLC)

DMSO : ≥ 34 mg/mL. 51.47 mM

FC(F)(F)OC1=CC=C2NC(=NC2=C1)C1=NC=C(OCCOCCOC2=CN=C(C=C2)C2=NC3=C(N2)C=CC(OC(F)(F)F)=C3)C=C1

2,2'-(((oxybis(ethane-2,1-diyl))bis(oxy))bis(pyridine-5,2-diyl))bis(5-(trifluoromethoxy)-1H-benzo[d]imidazole)

(-20℃)

With Ice Pack

≥ 2 years