American Association for Cancer Research
10780432ccr163083-sup-174902_1_supp_3907792_qmrtks.xlsx (106.35 kB)

Supplemental Table S1: PK small-molecule oncology from Clinically Relevant Concentrations of Anticancer Drugs: A Guide for Nonclinical Studies

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posted on 2023-03-31, 20:06 authored by Dane R. Liston, Myrtle Davis

An Excel file containing all small molecule drugs presented in Tables 1, 2 and 4 of the printed manuscript, including additional fields containing mechanism of action/target, MW, dose schedule, Tmax, Clearance, Volume of distribution, year approved, full references to source data and drug product label, approved indications, additional notes.



Approved and marketed drugs are frequently studied in nonclinical models to evaluate the potential application to additional disease indications or to gain insight about molecular mechanisms of action. A survey of the literature reveals that nonclinical experimental designs (in vitro or in vivo) often include evaluation of drug concentrations or doses that are much higher than what can be achieved in patients (i.e., above the maximally tolerated dose or much higher than the clinically relevant exposures). The results obtained with these high concentrations may be particularly helpful in elucidating off-target effects and toxicities, but it is critical to have a dose–response curve that includes the minimally effective or clinically effective concentration for comparison. We have reviewed the clinical literature and drug product labels for all small molecules and biological agents approved by the FDA for use in oncology to identify and compile the available pharmacokinetic parameters. The data summarized here can serve as a guide for selection of in vitro concentrations and in vivo plasma exposures for evaluation of drug effects in nonclinical studies. Inclusion of drug concentrations or exposures that are relevant to those observed in clinical practice can improve translation of nonclinical mechanism of action findings into potentially relevant clinical effects. Clin Cancer Res; 23(14); 3489–98. ©2017 AACR.