Table 1.

In vitro testing of temozolomide plus talazoparib (10 nmol/L)

Cell lineHistotypeTMZa rIC50 (μmol/L)TMZ rIC50 (mmol/L) with talazoparibPotentiation factorbYmin (observed)cRelative in/outd (observed Ymin)
RDRhabdomyosarcoma866.290.09.621.6817%
Rh41Rhabdomyosarcoma276.1114.42.44.29–81%
Rh18Rhabdomyosarcoma>1,000>1,0001.641.23–8%
Rh30eRhabdomyosarcoma3.45.10.72.38–86%
BT-12Rhabdoid812.3100.58.112.735%
CHLA-266Rhabdoid382.874.45.17.07–73%
TC-71Ewing sarcoma385.88.943.40.04–97%
CHLA-9Ewing sarcoma215.33.856.50.06–98%
CHLA-10Ewing sarcoma374.26.161.10.40–94%
CHLA-258Ewing sarcoma354.255.46.42.76–93%
GBM2eGlioblastoma359.84.285.30.72–93%
NB-1643eNeuroblastoma4.72.42.01.79–92%
NB-EBc1Neuroblastoma258.415.017.30.37–98%
CHLA-90Neuroblastoma994.8175.55.722.55–19%
CHLA-136Neuroblastoma275.028.39.79.67–66%
NALM-6ALL362.49.139.80.01–100%
COG-LL-317ALL207.1152.51.40.02–100%
RS4;11ALL369.618.320.20.43–97%
MOLT-4ALL412.011.735.30.01–100%
CCRF-CEMALL590.019.829.80.09–99%
Kasumi-1AML462.172.66.41.37–95%
Karpas-299ALCL383.313.528.50.64–92%
Ramos-RA1NHL414.524.616.90.20–80%
Median374.219.89.70.72–93%
Minimum3.42.40.70.01–100%
Maximum>1,000>1,00085.341.2317%

Abbreviations: AML, acute myeloid leukemia; ALCL, anaplastic large cell lymphoma; NHL, Non-Hodgkin lymphoma.

  • aTMZ, temozolomide.

  • bRatio of temozolomide rIC50 in the absence and presence of talazoparib (10 nmol/L).

  • cYmin (observed) for temozolomide in the presence of 10 nmol/L talazoparib. See Materials and Methods for definition.

  • dRelative in/out % (observed Ymin) for temozolomide in the presence of 10 nmol/L talazoparib. See Materials and Methods for definition.

  • eMGMT-negative cell lines.