grk in 1

4-Amino-5-(bromomethyl)-2-methylpyrimidine is a heterocyclic building block.1,2 It has been used in the synthesis of vitamin B1 analogs and thiaminephosphoric acid esters. |1. Abblard, J., Cronenberger, L., and Pacheco, H. Synthesis of the analogs of vitamin B1. Chim. Ther. 8(1), 98-110 (1973).|2. Leichssenring, G., and Joachim, S. The synthesis of thiaminephosphoric acid esters. Chem. Ber. 95, 767-772 (1962).

GRKs-IN-1 hydrochloride has remarkable potency against and selectivity for G protein-coupled receptor kinase 2 GRK2 (IC50: 130 nM) and GRK5 (IC50: 7.1 μM).

GRK6-IN-1 (compound 18) is a potent inhibitor of G protein-coupled receptor kinase 6 (GRK6) with an IC50 of 120 nM, and has potential for study in multiple myeloma.

GRK2 degrader-1 (compound 1) is a potent and orally active GRK2 degrader. It facilitates the degradation of GRK2 via the ubiquitin-proteasome pathway. In a pulmonary arterial hypertension (PAH) mouse model, GRK2 degrader-1 inhibits right ventricular remodeling and the increase in pulmonary arterial pressure. This compound is suitable for research in pulmonary arterial hypertension (PAH).