2416130-57-7
Chemical Structure
NRX-0492
- CAS No.: 2416130-57-7
- Formula:C43H51N11O6
- Molecular Weight:817.94
IUPAC Name: 3-((4-(1-(((3S)-1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)pyrrolidin-3-yl)methyl)piperidin-4-yl)phenyl)amino)-5-((R)-3-(3-methyl-2-oxoimidazolidin-1-yl)piperidin-1-yl)pyrazine-2-carboxamide
InChIKey: WFDYOAWNEOGIPM-NJZOVTIDSA-N
SMILES: NC(C1=C(N=C(N2CCC[C@@H](N3CCN(C)C3=O)C2)C=N1)NC(C=C4)=CC=C4C(CC5)CCN5C[C@@H](C6)CCN6C7=CC=C(C(C(N8C9C(NC(CC9)=O)=O)=O)=C7)C8=O)=O
Biological Activity: NRX-0492 is an orally active BTK PROTAC degrader, with a binding IC50 of 1.2 nM for both wild-type BTK and BTKT474I, and 2.7 nM for BTKC481S, and exhibits cellular DC50 values of 0.1 nM and 0.2 nM against wild-type BTK and BTKC481S, respectively. NRX-0492 catalyzes the ubiquitination and proteasomal degradation of wild-type and drug-resistant mutant BTK by recruiting the CRBN E3 ubiquitin ligase complex. NRX-0492 inhibits the BCR signaling pathway and its downstream NF-κB/MYC transcriptional program, achieves rapid and sustained degradation in primary CLL cells, and exhibits extremely low cytotoxicity. NRX-0492 degrades BTK, inhibits tumor cell proliferation and activation, and significantly suppresses tumor growth in xenograft models. NRX-0492 can be used in research related to chronic lymphocytic leukemia and diffuse large B-cell lymphoma[1][2][3][4].
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NRX-0492 | 98.30% | NRX-0492 is an orally active BTK PROTAC degrader, with a binding IC50 of 1.2 nM for both wild-type BTK and BTKT474I, and 2.7 nM for BTKC481S, and exhibits cellular DC50 values of 0.1 nM and 0.2 nM against wild-type BTK and BTKC481S, respectively. NRX-0492 catalyzes the ubiquitination and proteasomal degradation of wild-type and drug-resistant mutant BTK by recruiting the CRBN E3 ubiquitin ligase complex. NRX-0492 inhibits the BCR signaling pathway and its downstream NF-κB/MYC transcriptional program, achieves rapid and sustained degradation in primary CLL cells, and exhibits extremely low cytotoxicity. NRX-0492 degrades BTK, inhibits tumor cell proliferation and activation, and significantly suppresses tumor growth in xenograft models. NRX-0492 can be used in research related to chronic lymphocytic leukemia and diffuse large B-cell lymphoma. | ||||||||||||||||||||
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- [1]. Zhang D, et al. Highly potent BTK degradation induced by NRX0492 as a therapeutic strategy for CLL[J]. Blood, 2019, 134: 174.
- [2]. Zhang D, et al. NRX-0492 degrades wild-type and C481 mutant BTK and demonstrates in vivo activity in CLL patient-derived xenografts. Blood. 2023 Mar 30;141(13):1584-1596. [Content Brief]
- [3]. Issahaku A R, et al. Camptothecin and its Analogues as Putative Bruton Tyrosine Kinase (BTK) Inhibitors in Cancer Therapy-Biophysical Simulations of Wild Type and C481S Mutation[J]. Journal of Cancer Biomoleculars and Therapeutics, 2024, 1(1): 59-71.
- [4]. Ren J, et al. Discovery of as a Potent and Orally Bioavailable BTK PROTAC Degrader Incorporating a Novel Benzisoxazole-Based CRBN Ligand for the Treatment of B-Cell Malignancies. Journal of medicinal chemistry. 2025 Aug 14;68(15):15960-15979. [Content Brief]
Keywords
