In HEK293 cells expressing human H1 receptors, astemizole reduced basal IP1 signaling in a concentration-dependent manner. Responses differed between wild-type receptor and secondary-pocket mutants. [1]
Astemizole also blocked hERG current in four laboratories. Corrected-concentration IC50 estimates differed across laboratories, so these results should be interpreted with their assay conditions and do not support target-selective activity. [3]
Astemizole binding pose at human H1 receptor
Biochemical assay · Engineered purified human H1R-mBRIL complex [1]
The structural model places astemizole in the orthosteric pocket with its methoxyphenyl group extending into a secondary pocket.
Literature-Reported Treatment Conditions
- Treatment concentration
- 10 μM during complex purification
- Method
- Cryo-EM and fitted structural model
- Reported limits
- Purification concentration is not a cellular dose or affinity estimate.
Methods and source locations
Compound reported in the paper: Astemizole
Named astemizole material; no equivalence to an Adooq lot or formulation is established.
Results Sec3, Sec5; Fig1b caption; Fig2b image/caption; Methods Sec12–16
Structural contacts: Cryo-EM model interpreted with Fig2b — Results Sec5; Fig2b
Suppression of H1-receptor signaling
Cell-based study · HEK293 cells transiently expressing wild-type or mutant human H1R [1]
Astemizole concentration-dependently reduced basal H1R signaling. Y87A and W103A mutants retained more activity than wild type at higher tested concentrations.
Literature-Reported Treatment Conditions
- Exposure duration
- 1 h ligand incubation at 37 °C
- Method
- IP-One Gq HTRF assay; wild-type and mutant responses compared
- Reported limits
- Vehicle is not specified in Sec18. No numeric IC50 taken from curves or unreadable SI Table2.
Methods and source locations
Compound reported in the paper: Astemizole
Named astemizole material; no equivalence to an Adooq lot or formulation is established.
Results Sec5; Fig2c image/caption; Methods Sec18
Basal H1R signaling: IP1 accumulation normalized to basal receptor activity; n=3 independent samples, mean ± SEM — Fig2c and caption; Methods Sec18
Concentration-dependent hEag1 current inhibition
Cell-based study · HEK293 cells stably expressing human Eag1 [2]
Astemizole induced concentration- and time-dependent current decay after channel opening.
Literature-Reported Treatment Conditions
- Treatment concentration
- 25 nM–5 μM in Fig1C; IC50 is an assay endpoint
- Exposure duration
- Repeated 1.5-s test pulses every 30 s until steady-state block
- Method
- Whole-cell patch clamp at room temperature; +80 mV from −70 mV
- Vehicle
- 0.1% DMSO; no discernible current effect in vehicle test (n=4)
- Reported limits
- Total drug exposure time was not fixed in the cited experiment.
Methods and source locations
Compound reported in the paper: Astemizole
Named astemizole material; no equivalence to an Adooq lot or formulation is established.
Results: Dose-dependent Inhibition; Fig1C–G; Materials and Methods
Steady-state hEag1 current block: Mono-exponential fits of drug/control current ratios followed by concentration-response analysis — Results: Dose-dependent Inhibition, paragraph after Fig1 caption; Fig1E
Astemizole hERG block across laboratories
Cell-based study · Stable hERG1a-expressing CHO cells (Lab1) and HEK293 cells (Labs2,4,5) [3]
Astemizole inhibited hERG current in four laboratories, with different corrected-concentration IC50 point estimates.
Literature-Reported Treatment Conditions
- Method
- Manual whole-cell patch clamp near physiological temperature; 0.2-Hz step-ramp protocol; baseline and terminal E-4031-sensitive current controls
- Reported limits
- Exact astemizole concentration grids, exposure duration and vehicle are not extracted. Concentrations were analytically corrected; IC50 values are not treatment doses.
Methods and source locations
Compound reported in the paper: Astemizole
Named astemizole material; no equivalence to an Adooq lot or formulation is established.
Methods Sec3–6, Sec8–10; Results Sec17; Fig4; Supplementary Material1 Tables1,2,6
hERG outward ramp-current inhibition: Hill fits after correction for measured drug concentrations/loss; four laboratories — Supplementary Material1, Supplemental Table6 row21, columns B,F,N,R; units/CI footnote row36; main Fig4
