Snyder Christopher
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View article: Ex vivo drug susceptibility.
Ex vivo drug susceptibility. Open
Median 50% inhibitory concentrations (IC50s) of standard antimalarials and ACT-451840 in P. falciparum (closed symbols; n = 27) and P. vivax (open symbols; n = 34) clinical isolates.
View article: Correlation of the observed survival or antimalarial activity versus modeled maximal effect relationship.
Correlation of the observed survival or antimalarial activity versus modeled maximal effect relationship. Open
Correlation of the observed survival or antimalarial activity versus modeled maximal effect relationship.
View article: <i>P</i>. <i>falciparum</i> dual gamete formation assay.
<i>P</i>. <i>falciparum</i> dual gamete formation assay. Open
The effect of ACT-451840 on the functional viability of P. falciparum male and female gametocytes was tested in vitro in dose response. Male gametocyte viability was reported by microscopic detection of exflagellation centers and yielded a…
View article: In vitro activity against a panel of resistant and sensitive strains of <i>P</i>. <i>falciparum</i>.
In vitro activity against a panel of resistant and sensitive strains of <i>P</i>. <i>falciparum</i>. Open
In vitro activity against a panel of resistant and sensitive strains of P. falciparum.
View article: PK/PD strategy.
PK/PD strategy. Open
Workflow of PK and PD modeling approach towards human efficacious dose prediction. Abbreviations: maximum observed plasma concentration (Cmax) and, area under the concentration versus time curve (AUC).
View article: Time-, stage-, and concentration-dependent effects of ACT-451840 on synchronous cultures of <i>P</i>. <i>falciparum</i> NF54 in vitro.
Time-, stage-, and concentration-dependent effects of ACT-451840 on synchronous cultures of <i>P</i>. <i>falciparum</i> NF54 in vitro. Open
Parasites were exposed to ACT-451840 for 6 or 24 h at the indicated concentration. Results are expressed as the percentage of growth of the respective development stage relative to an untreated control. Each bar represents the mean + SD of…
View article: ACT-451840 blocking transmission.
ACT-451840 blocking transmission. Open
Standard membrane feeding assays were performed with a 24 h pre-incubation of gametocytes with compound (indirect mode). (A) shows average oocyst intensity per mosquito and (B) shows average oocyst prevalence (percentage of mosquitoes with…
View article: Survival days of <i>P</i>. <i>berghei</i> infected mice plotted against AUC, C<sub>max</sub>, and time above threshold over the entire treatment period (1 or 3 d).
Survival days of <i>P</i>. <i>berghei</i> infected mice plotted against AUC, C<sub>max</sub>, and time above threshold over the entire treatment period (1 or 3 d). Open
Dots are the observed days of survival; the line is the modeled relationship using a maximal effect (Emax) model.
View article: Therapeutic efficacy against <i>P</i>. <i>falciparum</i> in vivo.
Therapeutic efficacy against <i>P</i>. <i>falciparum</i> in vivo. Open
Parasitemia in peripheral blood of mice infected with P. falciparum NF540230/N3 and treated with vehicle, chloroquine, or ACT-451840 once daily for 4 d starting on Day 3 after infection. Data shown are mean parasitemia of three mice/group.…
View article: Pharmacokinetics parameters of ACT-451840 in healthy mice (<i>n</i> = 4).
Pharmacokinetics parameters of ACT-451840 in healthy mice (<i>n</i> = 4). Open
Pharmacokinetics parameters of ACT-451840 in healthy mice (n = 4).
View article: Antimalarial activity in <i>P</i>. <i>berghei</i> infected mice plotted against AUC, C<sub>max</sub>, and time above threshold over the entire treatment period (1 or 3 d).
Antimalarial activity in <i>P</i>. <i>berghei</i> infected mice plotted against AUC, C<sub>max</sub>, and time above threshold over the entire treatment period (1 or 3 d). Open
Dots are the observed antimalarial activity; the line is the modeled relationship using a maximal effect (Emax) model.
View article: ATR inhibition is synthetic lethal with pharmacologic inhibition of PARP.
ATR inhibition is synthetic lethal with pharmacologic inhibition of PARP. Open
(A) U2OS cells were treated with increasing doses of ATR and PARP inhibitors for 96 hours. Cell viability was measured with alamar blue and reported as a percent of the untreated control. Synergy between ATR and PARP inhibition using Bliss…