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. 2022 Jan 10;24(1):62–73. doi: 10.1038/s41556-021-00807-6

Extended Data Fig. 9. PARP inhibitors synergise with p97 inhibition.

Extended Data Fig. 9

a. and b. Bliss synergy calculation, performed with the Combenefit software (CRUK Cambridge Institute), of the drug-response curves shown in Fig. 6b, c. c. and d. Drug-response curves for the colony formation assays presented in Fig. 6a. CAL51 WT or PARP1−/− cells were treated with increasing concentrations of the PARP inhibitor Olaparib in the presence of either 100 nM CB-5083 (A) or 8 nM CuET (B). Surviving fractions were calculated based on the number of colonies after 14 days of exposure to the drugs. Shown are the mean ± SD of n = 3 biological replicas. e. A quantification of the CB-5083 single agent effect on the surviving fraction of DLD1 and DLD1 BRCA2−/− cells, respectively. Shown are the mean ± SD of n = 3 biological replicas. f. Colony formation assays showing the synergistic effect between talazoparib and CB-5083 in DLD1 and DLD1 BRCA2−/− cellular models. g. Area under the curve (AUC) analysis of the surviving fractions of DLD1 and DLD1 BRCA2−/− cells in the presence of increasing concentrations CB-5083 combination as presented in Fig. 6f. Shown are the mean ± SD of n = 3 biological replicates; ordinary one-way ANOVA **** - p < 0.0001. h. Bright-field images, showing the effect of talazoparib-CB-5083 combination on the GEMM WB1P organoid as described in Fig. 6g. Scale bar = 200 µm. Data shown represent 2 biological replicas. i. Bright-field images showing the effect of talazoparib-CB-5083 combination on the KCL014BCPO organoid as described in Fig. 6h. Scale bar = 200 µm. Data shown represent 3 biological replicas.