| Identification | Back Directory | [Name]
2-Pyrazinecarboxamide, 3-[[4-[1-[[1-[6-[[[(3S)-2,6-dioxo-3-piperidinyl]amino]carbonyl]-3-pyridinyl]-4-piperidinyl]methyl]-4-piperidinyl]phenyl]amino]-5-[(3R)-3-(3-methyl-2-oxo-1-imidazolidinyl)-1-piperidinyl]- | [CAS]
2649400-34-8 | [Synonyms]
NX-5948
BTK-IN-24(NX-5948)
3-[[4-[1-[[1-[6-[[(S)-2,6-Dioxo-3-piperidyl]carbamoyl]-3-pyridyl]-4-piperidyl]methyl]-4-piperidyl]phenyl]amino]-5-[(R)-3-(3-methyl-2-oxoimidazolidin-1-yl)-1-piperidyl]pyrazine-2-carboxamide
3-((4-(1-((1-(6-(((S)-2,6-dioxopiperidin-3-yl)carbamoyl)pyridin-3-yl)piperidin-4-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-[[1-[6-[[[(3S)-2,6-dioxo-3-piperidinyl]amino]carbonyl]-3-pyridinyl]-4-piperidinyl]methyl]-4-piperidinyl]phenyl]amino]-5-[(3R)-3-(3-methyl-2-oxo-1-imidazolidinyl)-1-piperidinyl]- | [Molecular Formula]
C42H54N12O5 | [MOL File]
2649400-34-8.mol | [Molecular Weight]
806.96 |
| Chemical Properties | Back Directory | [Boiling point ]
1052.9±65.0 °C(Predicted) | [density ]
1.41±0.1 g/cm3(Predicted) | [form ]
Solid | [pka]
10.60±0.40(Predicted) | [color ]
Off-white to light yellow |
| Hazard Information | Back Directory | [Uses]
NX-5948 (BTK-IN-24) 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. NX-5948 mediates potent anti-inflammatory activity via BTK degradation with resultant inhibition of B cell activation. NX-5948 exhibits potent tumor growth inhibition in TMD8 xenograft models that contain either wild-type BTK or BTKi-resistant mutations. NX-5948 is efficacious in a mouse collageninduced arthritis (CIA) model. NX-5948 can cross the blood brain barrier (BBB). NX-5948 is a PROTAC composed of the ligand for target protein, a linker, and a cereblon E3 ligase (CRBN) complex (Red: ligand for target protein; Blue: CRBN; Black: linker)[1][2][3]. | [in vivo]
NX-5948 (BTK-IN-24; 10, 30 mg/kg; po; daily; Day 18 to 36) is efficacious and well-tolerated in a mouse collagen-induced arthritis (CIA) model and suppresses antibody titers and IL-6 cytokine levels[1].
NX-5948 (3, 10, 30 mg/kg; po) causes dose- and time-dependent reduction in BTK levels in circulating murine and non-human primate, cynomolgus monkey B cells[1].
| Animal Model: | Mouse collagen-induced arthritis (CIA) model[1] | | Dosage: | 10, 30 mg/kg | | Administration: | PO; daily; Day 18 to 36 | | Result: | Showed efficacious and well-tolerated in a mouse CIA model.
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| [IC 50]
Cereblon | [References]
[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. DOI:10.1186/s43556-022-00112-0 |
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