Sevabertinib

Sevabertinib is a dual inhibitor of wild-type and exon 20 insertion (ex20ins) mutation-containing EGFR and HER2 (IC50s = <0. nM for EGFR, EGFR exon20 D770 insSVD, HER2, and HER2 exon20 A775 insYMVA). It is selective for these proteins over HER4 (IC50 = 13. nM). Sevabertinib (0.01-1 µM) reduces the viability of A431, NCI-H2170, NCI-H1781, and MDA-MB-175-VII cells endogenously expressing EGFR or HER2 wild-type or insertion mutant gene amplifications. In vivo, sevabertinib (5 and 10 mg/kg) reduces tumor growth in a HER2 exon20 A775 insYMVA mutant-containing CTG-2543 patient-derived xenograft (PDX) mouse model. Formulations containing sevabertinib have been used in the treatment of non-small cell lung cancer (NSCLC). Formal Name: 3-[(3-chloro-2-methoxyphenyl)amino]-2-[3-[(2S)-1,4-dioxan-2-ylmethoxy]-4-pyridinyl]-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-one. CAS Number: 2521285-05-0. Synonyms: BAY-2927088. Molecular Formula: C24H25ClN4O5. Formula Weight: 484.9. Purity: >98%. Formulation (Request formulation change): A solid. Solubility: DMSO: Soluble: >10 mg/ml Ethanol: Sparingly soluble: 1-10 mg/ml. SMILES: O=C(NCC1)C2=C1NC(C3=CC=NC=C3OC[C@H]4OCCOC4)=C2NC5=C(C(Cl)=CC=C5)OC. InChi Code: InChI=1S/C24H25ClN4O5/c1-31-23-16(25)3-2-4-18(23)29-22-20-17(6-8-27-24(20)30)28-21(22)15-5-7-26-11-19(15)34-13-14-12-32-9-10-33-14/h2-5,7,11,14,28-29H,6,8-10,12-13H2,1H3,(H,27,30)/t14-/m0/s1. InChi Key: VYQVHWNNPKOJEA-AWEZNQCLSA-N. Storage: -20°C. Stability: > 4 years.