Meyd-773 __full__

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A combinatorial library of 1,3‑thiazolo[5,4‑d]pyrimidine derivatives was screened for PI3K inhibition. MEYD‑773 (chemical name: 6‑[(4‑fluorophenyl)amino]‑2‑(pyridin‑3‑yl)‑1,3‑thiazolo[5,4‑d]pyrimidine) was identified as the lead compound (IC₅₀ = 12 nM for p110α). Kinase selectivity was assessed against a 340‑kinase panel. Cellular activity was evaluated in a panel of breast cancer cell lines (MDA‑MB‑231, HCC‑1806, BT‑549, MCF‑7, and T‑47D). Apoptosis, cell‑cycle distribution, and downstream signaling were examined by flow cytometry, western blot, and phospho‑proteomics. Pharmacokinetics (PK) and tolerability were studied in CD‑1 mice. Antitumor efficacy was tested in orthotopic TNBC xenografts and patient‑derived xenograft (PDX) models.

MEYD‑773 displayed >250‑fold selectivity for class I PI3K over other kinases, with negligible activity against mTOR, DNA‑PK, and CDK families. In vitro, MEYD‑773 reduced p‑AKT (Ser473) and p‑S6 (Ser235/236) levels with EC₅₀ ≈ 30 nM, induced G₁ arrest, and triggered caspase‑3/7‑mediated apoptosis selectively in PI3K‑mutant TNBC cells (IC₅₀ = 0.08‑0.15 µM). PK studies revealed oral bioavailability of 68 %, a half‑life of 7.2 h, and plasma exposure exceeding the in‑vitro EC₅₀ for >12 h at 20 mg kg⁻¹. In orthotopic MDA‑MB‑231 models, daily oral dosing (20 mg kg⁻¹) produced a tumor growth inhibition (TGI) of 82 % (p < 0.001) without weight loss or histopathologic toxicity. In three independent TNBC PDX models (BRCA1‑mutated, PTEN‑null, and wild‑type PI3K), MEYD‑773 achieved TGIs of 71‑89 % and prolonged median survival by 3‑4‑fold compared with vehicle. Combination with standard‑of‑care paclitaxel showed synergistic tumor regression (Combination Index = 0.46). MEYD-773

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MEYD‑773: A Novel Small‑Molecule Inhibitor of the PI3K/AKT Pathway with Potent Activity against Triple‑Negative Breast Cancer : It's possible that "MEYD-773" pertains to a

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The crew lived in a tightly knit community. Weekly “cultural nights” featured cuisine and music from the many nations represented onboard, and a rotating “Storytime” where senior crew members recounted tales of early spaceflight—both to preserve history and to remind everyone why they were venturing into the unknown.

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The crew responded with a unified “Affirmative,” their visors flashing green as they each completed the final biometric verification.

MEYD‑773, PI3K inhibitor, triple‑negative breast cancer, targeted therapy, preclinical development