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. 2019 Jan 3;104(6):1209–1220. doi: 10.3324/haematol.2018.201483

Figure 1.

Figure 1.

ARV 825 anti-proliferative activities: MTT and clonogenic growth of multiple myeloma (MM) cells. (A) Structures of the two proteolysis targeting chimeric molecules (PROTAC) used in this study: ARV 825 and MZ1. (B) Growth inhibition of KMS11 and KMS28BM cells treated with pomalidomide (1 μM-20 μM), OTX015 (1 μM-10 μM), and ARV 825 (1 nM-1000 nM) for 72 hours (h). Results are Mean±Standard Deviation (SD); three experiments were carried out in triplicate. (C) MM cells were treated with ARV 825 (1 nM-500 nM, 72 h). Growth inhibition was measured by MTT assay. Results are Mean±SD; n=3. IC50s are shown in Online Supplementary Table S1. (D) ARV 825 decreased clonogenic growth of KMS11 and KMS28BM cells. Mean±SD of two independent experiments carried out in triplicates. Student t-test, **P≤0.001; ***P≤0.0001. (E) MM cells treated with PROTAC MZ1 (VHL E3 ligase fused to JQ1; 1-1000 nM, 72 h, and measured by MTT assay). Results represent Mean±SD of three experiments carried out in triplicate. IC50s are shown in Online Supplementary Table S2. (F) Primary patient samples (Patient 1, Patient 2, Patient 3) treated with ARV 825 (10-300 nM, 72 h). Growth inhibition measured by luminescence cell viability assay. Results are Mean±SD; n=3.