Bexobrutideg

Bexobrutideg (NX-5948) is an orally active chimeric targeting molecule (CTM) that induces specific BTK protein degradation by the cereblon E3 ligase (CRBN) complex without degradation of other cereblon neo-substrates. Bexobrutideg mediates potent anti-inflammatory activity via BTK degradation with resultant inhibition of B cell activation. Bexobrutideg exhibits potent tumor growth inhibition in TMD8 xenograft models that contain either wild-type BTK or BTKi-resistant mutations. Bexobrutideg is efficacious in a mouse collageninduced arthritis (CIA) model. Bexobrutideg can cross the blood brain barrier (BBB) . Bexobrutideg is a PROTAC composed of the ligand for target protein, a linker, and a cereblon E3 ligase (CRBN) complex (Red: BTK ligand (HY-170324) ; Blue: CRBN ligand (HY-171893) ; Black: linker) [1][2][3].

Product Specifications

CAS Number

[2649400-34-8]

Product Name Alternative

NX-5948; BTK-IN-24

UNSPSC

12352005

Target

Btk; PROTACs

Type

Reference compound

Related Pathways

PROTAC; Protein Tyrosine Kinase/RTK

Applications

Cancer-Kinase/protease

Field of Research

Cancer; Inflammation/Immunology

Assay Protocol

https://www.medchemexpress.com/nx-5948.html

Purity

99.33

Solubility

DMSO : 100 mg/mL (ultrasonic)

Smiles

NC(C1=C(N=C(N2C[C@H](N3C(N(CC3)C)=O)CCC2)C=N1)NC4=CC=C(C5CCN(CC5)CC6CCN(C7=CN=C(C(N[C@@H]8C(NC(CC8)=O)=O)=O)C=C7)CC6)C=C4)=O

Molecular Formula

C42H54N12O5

Molecular Weight

806.96

References & Citations

[1]Mark Noviski, et al. NX-5948, a Selective Degrader of BTK, Significantly Reduces Inflammation in a Model of Autoimmune Disease. 2021 Nurix Therapeutics, Inc.|[2]4473 Initial Findings from a First-in-Human Phase 1a/b Trial of NX-5948, a Selective Bruton’s Tyrosine Kinase (BTK) Degrader, in Patients with Relapsed/Refractory B Cell Malignancies. Annual Meeting & Exposition, Monday, December 11, 2023.|[3]Zi Liu, et al. An overview of PROTACs: a promising drug discovery paradigm. Mol Biomed. 2022 Dec 20;3 (1) :46.