2416131-46-7

NX-2127 (compound 28) is an orally active PROTAC deggrader, targeting to Bruton’s Tyrosine Kinase (Btk) . NX-2127 inhibits proliferation of BTKC481S mutant TMD8 cells, more effectively than Ibrutinib (HY-10997). NX-2127 catalyzes the degradation of Ikaros (IKZF1) and Aiolos (IKZF3) with of 25 nM and 54 nM, respectively. NX-2127 stimulates T cell activation and increases IL-2 production in primary human T Cells[1][2]. NX-2127 is composed of PROTAC target protein ligand (red part) BTK ligand 10 (HY-168302), E3 ligase ligand (blue part) Thalidomide 5-fluoride (HY-W087383) and PROTAC Linker (black part) (S)-4-(1-(Pyrrolidin-3-ylmethyl)piperidin-4-yl)aniline (HY-168303). Among which, the conjugate of E3 ubiquitin ligase ligand + Linker compose of Thalidomide-pyrrolidine-C-piperidine-Ph-NH2 (HY-168304).

[1] Robbins D W, et al. Nx-2127, a degrader of BTK and IMiD neosubstrates, for the treatment of B-cell malignancies. Blood, 2020, 136: 34.
[2] Mato A, et al. A first-in-human phase 1 trial of NX-2127, a first-in-class oral BTK degrader with IMiD-like activity, in patients with relapsed and refractory B-cell malignancies. 2022.