Figure 3
Figure 3. Summary of A2A agonist/PDE inhibitor combination selectivity and breadth of activity. (A) Synergy scores were determined for 61 cell lines cells treated with HE-NECA and trequinsin and/or CGS-21680 and trequinsin combinations (see Figure 1 legend for details of how synergy scores were derived). GA-10, Raji, Farage, Pfeiffer, Toledo, Kasumi-1, HL-60, AoSMC, HCAEC, HUVEC, and all solid tumor cell lines were treated with HE-NECA and trequinsin. Jvm-13, Mino, EJM, H929, KSM-12-PE, MM.1R, MM.1S, Molp-2, Molp-8, OPM-2, RPMI-8226, U266, Sup-B15, and PBMCs were treated with HE-NECA/trequinsin and with CGS-21680/trequinsin. The rest of the cell lines received the combination of CGS-21680 and trequinsin. Synergistic activity was observed for the majority of the multiple myeloma cell lines examined. Strong combination activity was also observed in a subset of DLBCL cell lines tested. Synergy was not observed with either solid tumor or normal cells. (B) The single-agent dose response for HE-NECA was determined after 72-hour incubation in MM.1S, PBMC, HUVEC, and AoSMC. (C) The activity of increasing concentrations of HE-NECA was determined at a fixed concentration of 3.4μM trequinsin using MM.1S, PBMC, HUVEC, and AoSMC cells. (D) The activity of increasing concentrations of CGS-21680 was determined as a single agent or in combination with 3.4μM trequinsin using MM.1S and PBMC cells.

Summary of A2A agonist/PDE inhibitor combination selectivity and breadth of activity. (A) Synergy scores were determined for 61 cell lines cells treated with HE-NECA and trequinsin and/or CGS-21680 and trequinsin combinations (see Figure 1 legend for details of how synergy scores were derived). GA-10, Raji, Farage, Pfeiffer, Toledo, Kasumi-1, HL-60, AoSMC, HCAEC, HUVEC, and all solid tumor cell lines were treated with HE-NECA and trequinsin. Jvm-13, Mino, EJM, H929, KSM-12-PE, MM.1R, MM.1S, Molp-2, Molp-8, OPM-2, RPMI-8226, U266, Sup-B15, and PBMCs were treated with HE-NECA/trequinsin and with CGS-21680/trequinsin. The rest of the cell lines received the combination of CGS-21680 and trequinsin. Synergistic activity was observed for the majority of the multiple myeloma cell lines examined. Strong combination activity was also observed in a subset of DLBCL cell lines tested. Synergy was not observed with either solid tumor or normal cells. (B) The single-agent dose response for HE-NECA was determined after 72-hour incubation in MM.1S, PBMC, HUVEC, and AoSMC. (C) The activity of increasing concentrations of HE-NECA was determined at a fixed concentration of 3.4μM trequinsin using MM.1S, PBMC, HUVEC, and AoSMC cells. (D) The activity of increasing concentrations of CGS-21680 was determined as a single agent or in combination with 3.4μM trequinsin using MM.1S and PBMC cells.

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