Juy-108 [extra Quality] -

| Modality | Pros | Cons | |---|---|---| | | High specificity, long half‑life | Limited tissue penetration, intravenous administration | | Bispecific antibodies (VEGFR‑2/TIE2) | Simultaneous blockade, long half‑life | Complex manufacturing, high cost | | Small‑molecule kinase inhibitors | Oral dosing, rapid tissue distribution (including CNS), tunable pharmacokinetics | Potential off‑target activity, resistance mutations |

(Prepared April 10 2026 – all data current to the end of Q1 2026. Sources include peer‑reviewed publications, company filings, conference abstracts, and FDA/EMA public dossiers.) juy-108

| Chemical Moiety | Contribution | Optimization Path | |---|---|---| | | Provides ATP‑competitive binding to the hinge region of VEGFR‑2/TIE2 | S‑configuration critical for potency (IC₅₀ ≈ 1 nM vs. VEGFR‑2) | | (3‑F‑4‑Me‑phenyl)‑methyl substituent | Enhances hydrophobic contacts within the solvent‑exposed region, boosts oral bioavailability | Fluorine improves metabolic stability; methyl reduces oxidative de‑halogenation | | 2‑pyridin‑3‑yl‑pyrimidine | Drives selectivity for TIE2 by occupying a unique back‑pocket not present in VEGFR‑2 | Substituted pyridine improves solubility, mitigates off‑target kinase binding (e.g., PDGFR‑β) | | Modality | Pros | Cons | |---|---|---|