BC-DXI-843

Research use only, not for human use.

BC-DXI-843 is inhibitor of AIMP2-DX2, and is potential for development of novel therapeutics targeting AIMP2-DX2 in lung cancer.

BC-DXI-843 is inhibitor of AIMP2-DX2, and is potential for development of novel therapeutics targeting AIMP2-DX2 in lung cancer.Optimization of hit BC-DXI-04 (IC50 = 40.1 μM) provided new potent sulfonamide based AIMP2-DX2 inhibitors.?Among these, BC-DXI-843 showed improved inhibition against AIMP2-DX2 (IC50 = 0.92 μM) with more than 100-fold selectivity over AIMP2 in a luciferase assay.?Several binding assays indicated that this compound effectively induces cancer cell apoptosis by specifically interrupting the interaction between DX2 and HSP70, which leads to the degradation of DX2 via Siah1-mediated ubiquitination.BC-DXI-843 demonstrated in vivo efficacy in a tumor xenograft mouse model (H460 cells) at a dosage of 50 mg/kg, suggesting it as a promising lead for development of novel therapeutics targeting AIMP2-DX2 in lung cancer.

BC-DXI-843 (0.0316-31.6 μM; 72 hours) suppresses cancer cell proliferation in a DX2-dependent manner. The EC50 in A549 cells is 1.20 μM, which is similar to the IC50 for inhibition of DX2. However, no inhibition of WI-26 cells is observed, suggesting that BC-DXI-843 specifically reduces the viability of cancer cells. Cell Proliferation Assay Cell Line:A549 cancer cells and WI-26 normal cells Concentration:0.0316, 0.1, 0.316, 1, 3.16, 10, 31.6 μM Incubation Time:72 hours Result:The EC50 in A549 cells was 1.20 μM. No inhibition of WI-26 cells was observed.

BC-DXI-843 (50 mg/kg; intraperitoneally administered; every other day for 15 days) demonstrates in vivo efficacy in a tumor xenograft mouse model (H460 cells). Animal Model:7-week-old female BALB/cSLC-nu/nu mice bearing H460 cells xenograft Dosage:50 mg/kg Administration:Intraperitoneally administered; every other day for 15 days Result:The embedded tumor volume gradually declined after BC-DXI-843administration, but no changes in body weight were observed. The weight of the excised tumors after sacrifice had decreased in mice.

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Others

Other Targets

AIMP2-DX2

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2421117-98-6

546.66

C28H26N4O4S2

>98% (HPLC)

DMSO:245mg/ml (448.18 Mm; Need ultrasonic)

COC1=CC=C(C=C1)C1=CSC(NC(=O)[C@H](CC2=CNC3=CC=CC=C23)NS(=O)(=O)C2=CC=C(C)C=C2)=N1

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(-20℃)

With Ice Pack

≥ 2 years