Miaa-376 __hot__ Site

In a world teeming with codes and ciphers, "MIAA-376

| Model | Dose & Route | Tumor Growth Inhibition (TGI) | Survival Benefit | Key Observations | |-------|--------------|-------------------------------|------------------|------------------| | | 30 mg/kg PO daily (14 d) | 68 % (p < 0.001) | Median OS ↑ 3.2 wk vs. control | ↓ Ki‑67, ↑ cleaved caspase‑3 | | B16‑F10 (murine melanoma, syngeneic) | 25 mg/kg PO BID + anti‑PD‑1 (10 mg/kg i.p.) | 85 % (p < 0.0001) | 100 % long‑term survivors (≥ 90 d) | ↑ CD8⁺ T‑cell infiltration (CD45⁺CD8⁺) | | Patient‑Derived Xenograft (PDX) #23 (NRAS‑mutant) | 40 mg/kg PO QD | 55 % (p = 0.004) | Trend ↑ (not statistically powered) | Down‑regulation of EMT markers (Vimentin) | | Pharmacokinetics (mouse) | 30 mg/kg PO | Cmax ≈ 5 µM; t½ ≈ 7 h; AUC₀‑∞ ≈ 30 µM·h | — | Good oral bioavailability (~45 %). | MIAA-376

The safety profile appears acceptable for first‑in‑human (FIH) studies, especially given the projected Cmax of ~5 µM (≈ 2 µg/mL) in pre‑clinical efficacy models—far below the hERG IC₅₀. In a world teeming with codes and ciphers,