| Identification | Back Directory | [Name]
2-Pyrazinecarboxamide, 3-[[4-[1-[[(3S)-1-[2-(2,6-dioxo-3-piperidinyl)-2,3-dihydro-1,3-dioxo-1H-isoindol-5-yl]-3-pyrrolidinyl]methyl]-4-piperidinyl]phenyl]amino]-5-[(3R)-3-(3-methyl-2-oxo-1-imidazolidinyl)-1-piperidinyl]- | [CAS]
2416130-57-7 | [Synonyms]
NRX0492
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
2-Pyrazinecarboxamide, 3-[[4-[1-[[(3S)-1-[2-(2,6-dioxo-3-piperidinyl)-2,3-dihydro-1,3-dioxo-1H-isoindol-5-yl]-3-pyrrolidinyl]methyl]-4-piperidinyl]phenyl]amino]-5-[(3R)-3-(3-methyl-2-oxo-1-imidazolidinyl)-1-piperidinyl]- | [Molecular Formula]
C43H51N11O6 | [MOL File]
2416130-57-7.mol | [Molecular Weight]
817.94 |
| Chemical Properties | Back Directory | [density ]
1.395±0.06 g/cm3(Predicted) | [form ]
Solid | [pka]
10.83±0.40(Predicted) | [color ]
Light yellow to yellow | [InChIKey]
WFDYOAWNEOGIPM-NJZOVTIDSA-N | [SMILES]
C1(C(N)=O)=NC=C(N2CCC[C@@H](N3C(=O)N(C)CC3)C2)N=C1NC1=CC=C(C2CCN(C[C@@H]3CCN(C4C=CC5=C(C=4)C(=O)N(C4CCC(=O)NC4=O)C5=O)C3)CC2)C=C1 |
| Hazard Information | Back Directory | [Uses]
NRX-0492 is an orally active PROTAC-class BTK degrader. NRX-0492 catalyzes BTK ubiquitination and proteasome degradation (DC50 ≤ 0.2 nM, DC90 ≤ 0.5 nM)[1]. NRX-0492 inhibits B cell receptor (BCR) mediated signaling, transcription programs, and chemokine secretion. NRX-0492 can bind non-covalently to the BTK binding domain and cereblon, which is an adapter protein in the E3 ubiquitin ligase complex[1]. NRX-0492 consists of a target protein ligand (red part) BTK-IN-40 (HY-170324), an E3 ligase ligand (blue part) Thalidomide 5-fluoride (HY-W087383), and a PROTAC linker (black part) (3R)-3-Pyrrolidinemethanol (HY-60263). E3 ubiquitin ligase and linker can form Thalidomide 5-pyrrolidine-CHO (HY-49372A); the active control for the target protein ligand is BTK ligand 12 (HY-49421). | [References]
[1] 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. DOI:10.1182/blood.2022016934 |
|
|