ACD856 (IGF-1R Modulator 1) Research Standard

ACD856 (IGF-1R Modulator 1), chemically identified as 1-(3-methyl-4-phenoxyphenyl)-3-phenyl-1,3,5-triazinane-2,4,6-trione (CAS 2375424-89-6), is a triazinetrione-class research compound characterized in the scientific literature as a pan-Trk positive allosteric modulator. It serves as a pharmacological tool for investigating neurotrophin receptor signaling — the TrkA, TrkB, and TrkC receptors activated by NGF and BDNF — and for comparative receptor profiling against the structurally related IGF-1R and FGFR1 receptor tyrosine kinases. In controlled laboratory environments, ACD856 allows researchers to observe how allosteric modulation shapes receptor kinase activity, downstream ERK1/2 signaling, and synaptic protein expression in cellular and neural models.

Technical Specifications

Mechanism of Action & Research Context

ACD856 is investigated for its capacity to positively modulate the activity of neurotrophin receptors rather than activate them directly.

• Pan-Trk Positive Allosteric Modulation: Cell-based reporter assays on this compound register EC50 values of approximately 0.38 µM at TrkA, 0.29 µM at TrkB, and 0.33 µM at TrkC, with maximum effects of 185%, 176%, and 328% of the activation reached by the natural ligand alone. Published characterization of the same molecule reports an increase in the apparent Vmax of TrkA kinase activity, consistent with enhanced NGF- and BDNF-stimulated receptor signaling rather than direct receptor activation.

• Receptor Selectivity Profiling: In the same assay series the compound registers EC50 values of approximately 0.19 µM at FGFR1 and 0.25 µM at IGF-1R, the two most potent values in the set, while their maximum effects reach only 117% and 104% against 176–328% at the neurotrophin receptors. Published work describes this as a selectivity toward neurotrophin receptors with respect to efficacy rather than potency. This separation of potency from efficacy makes it a useful probe for dissecting selectivity between Trk receptors and related receptor tyrosine kinases.

• Downstream Signaling: Researchers employ ACD856 to examine potentiation of ERK1/2 phosphorylation, neurite outgrowth, and pre-synaptic protein expression (such as SNAP25) in in vitro neuronal models.

Research Applications

ACD856 is a specialized reagent for modern neurotrophin signaling and receptor pharmacology research.

Primary fields of in vitro laboratory investigation include:

• Neurotrophin Receptor Assays: Quantifying TrkA/TrkB/TrkC phosphorylation and kinase kinetics under allosteric modulation.

• BDNF/NGF Potentiation Studies: Measuring how sub-threshold neurotrophin concentrations are amplified in primary neuronal cultures.

• Comparative RTK Pharmacology: Benchmarking potency and efficacy across Trk receptors, IGF-1R, and FGFR1 to map allosteric selectivity.

• Structure–Activity Relationship (SAR) Studies: Comparing substituted 1,3,5-triazinane-2,4,6-trione analogs to characterize how aryl substitution shapes modulator potency.

• Analytical Reference Work: Serving as a reference material for chromatographic and mass-spectrometric identification and method development.

Storage & Handling Guidelines

Store at controlled room temperature. Keep tightly closed. Liquid formats: do not refrigerate or freeze. Cold storage may cause the solution to cloud or precipitate. If this occurs, return to room temperature and mix until clear.

Storage guidance is a house recommendation. Analytical documentation is per-lot release testing.