Iptd-694 Jun 2026

Mechanistic studies suggested that BET inhibition led to down‑regulation of MYC and BCL‑XL, while NLRP3 suppression decreased tumor‑associated inflammation, thereby sensitizing tumors to immune checkpoint blockade.

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| Species | Study Type | NOAEL (mg/kg) | Observations | |---------|------------|---------------|--------------| | | 5, 15, 50 mg/kg/day | 15 mg/kg/day | No clinical signs; mild hepatic vacuolation at 50 mg/kg (reversible) | | Dog (90‑day repeat dose, PO) | 2, 6, 20 mg/kg/day | 6 mg/kg/day | No mortality; transient ↑ ALT/AST at 20 mg/kg (≤2‑fold) | | Genotoxicity | Ames, mouse lymphoma, micronucleus | — | Negative in all assays | | Cardiovascular safety | hERG assay, telemetry in dogs | IC₅₀ > 30 µM; no QTc prolongation at 10× projected human Cmax | Low pro‑arrhythmic risk | | Reproductive toxicity | Rat embryo‑fetal development (GD 6‑15) | NOAEL 10 mg/kg/day | No teratogenicity; slight decrease in fetal weight at 30 mg/kg (stat. sig.) | | Safety pharmacology (CNS) | Irwin test, locomotor activity | 30 mg/kg (single) | No sedation, ataxia, or seizure activity | Mechanistic studies suggested that BET inhibition led to