Migd-061 !!better!! -

– MIGD‑061 demonstrates a favorable pre‑clinical toxicology profile with a therapeutic index > 30 × the projected clinical exposure (Cmax at 30 mg). The most consistent signal is a mild, reversible hepatic enzyme elevation , which appears dose‑related but manageable with routine monitoring.

| Parameter | Reported Value / Comment | |-----------|---------------------------| | | N ‑[(4‑fluorophenyl)‑2‑pyrimidinyl]‑2‑[(1‑oxo‑1,3‑dihydro‑isoindol‑2‑yl)‑methyl]‑acetamide | | Molecular weight | 421.4 Da | | Core scaffold | Pyrimidine‑linked benzamide with an isoindolinone side‑chain; designed for high‑affinity binding in the GCN2 kinase pocket. | | Solubility | ~30 µM in pH 7.4 phosphate buffer (reported in pre‑clinical DMPK). | | Permeability | High (Papp > 10 × 10⁻⁶ cm/s in Caco‑2 assay). | | Metabolism | Predominantly CYP3A4 mediated O‑dealkylation; major metabolite is a hydroxy‑isoindolinone (inactive in vitro). | | Half‑life (rat) | 4.2 h (oral); 2.8 h (IV). | | Bioavailability | 62 % after a 10 mg/kg oral dose (fasted rats). | | Plasma protein binding | 96 % (human). | | Key ADME findings | Low risk of drug‑drug interaction (weak reversible inhibition of CYP2C9, CYP2D6; no time‑dependent inhibition of CYP3A4). | migd-061

The ISR orchestrates cellular adaptation to amino‑acid deprivation, oxidative stress, and viral infection. Hyper‑activation of GCN2 has been linked to tumor immune evasion (via PD‑L1 up‑regulation), chronic neurodegeneration, and viral replication. Consequently, selective GCN2 inhibition is being explored for oncology, neuro‑inflammation, and infectious disease. | | Solubility | ~30 µM in pH 7

Total Addressable Market (TAM) for the combined indications exceeds , with | | Half‑life (rat) | 4