Lead Identification of Novel Naphthyridine Derivatives as Potent SOS1 Inhibitors.

SOS1, a guanine nucleotide exchange factor (GEF), plays a critical role in catalyzing the conversion of KRAS from its GDP- to GTP-bound form, regardless of mutation status, and represents a promising new drug target to treat all KRAS-driven tumors. Herein, we employed a scaffold hopping strategy to design, synthesize, and optimize a series of novel binary ring derivatives as SOS1 inhibitors. Among them, compound (HH0043) displayed potent activities in both biochemical and cellular assays and favorable pharmacokinetic profiles.

Clean prediction of CP-violating processes psi, phi, and Gamma decay to KSKS and KLKL.

The ratio of K(S)K(S) (K(L)K(L)) and K(L)K(L) production rates is calculated by considering K(0) - K(0) oscillation in J/psi --> K(0)K(0) decay. The theoretical uncertainty due to strong interaction in J/psi decay is completely canceled in the ratio; therefore, the absolute branching fractions of the CP-violating processes of J/psi --> K(S)K(S) and K(L)K(L) can be cleanly and model-independently determined in the case that J/psi K(S)K(L) decay is precisely measured. In the future tau-charm factory, the expected CP violating process of J/psi --> K(S)K(S) should be reached.