PRN1008 CAS 1575596-29-0

Introduction：Basic information about PRN1008 CAS 1575596-29-0, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

PRN1008 Basic information

• Product Name: PRN1008
• Synonyms: PRN-1008-E;1-Piperidinepropanenitrile, 3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]-α-[2-methyl-2-[4-(3-oxetanyl)-1-piperazinyl]propylidene]-β-oxo-, (αE,3R)-;Rilzabrutinib;Rilzabrutinib (PRN-1008);PRN-1008,inhibit,Rilzabrutinib,PRN 1008,Inhibitor,Btk,Bruton tyrosine kinase;(R,E)-2-(3-(4-amino-3-(2-fluoro-4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidine-1-carbonyl)-4-methyl-4-(4-(oxetan-3-yl)piperazin-1-yl)pent-2-enenitrile;Rilzabrutinib, 10 mM in DMSO;Rilzabrutinb
• CAS: 1575596-29-0
• MF: C36H40FN9O3
• MW: 665.77
• Mol File: 1575596-29-0.mol

PRN1008 Chemical Properties

• Boiling point: 882.5±65.0 °C(Predicted)
• density: 1.39±0.1 g/cm3(Predicted)
• storage temp.: Store at -20°C
• solubility: DMSO:120.0(Max Conc. mg/mL);180.24(Max Conc. mM)
• form: Solid
• pka: 6.24±0.70(Predicted)
• color: White to off-white
• InChIKey: LCFFREMLXLZNHE-CNPRKNKUNA-N
• SMILES: NC1N=CN=C2N([C@@H]3CCCN(C(=O)/C(/C#N)=C/C(N4CCN(C5COC5)CC4)(C)C)C3)N=C(C3C=CC(OC4C=CC=CC=4)=CC=3F)C=12 |&1:7,r|

PRN1008 Usage And Synthesis

Uses

Rilzabrutinib (PRN1008) is a reversible covalent, selective and oral active inhibitor of Bruton’s Tyrosine Kinase (BTK), with an IC50 of 1.3 nM.

in vivo

In vivo Rilzabrutinib demonstrates enduring pharmacodynamic effects after the compound has cleared from circulation, consistent with extended target residence time. Rilzabrutinib also reverses and completely suppresses collagen-induced arthritis in rats in a dose dependent manner which allows correlation of target occupancy and disease modification^[2].

IC 50

BTK: 1.3 nM (IC₅₀); BMX: 1.0 nM (IC₅₀); ITK: 440 nM (IC₅₀); TEC: 0.8 nM (IC₅₀); RLK: 1.2 nM (IC₅₀); BLK: 6.3 nM (IC₅₀); EGFR: 520 nM (IC₅₀); ERBB2: 3900 nM (IC₅₀); ERBB4: 11.3 nM (IC₅₀)

References

[1] Smith PF, et al. A phase I trial of PRN1008, a novel reversible covalent inhibitor of Bruton's tyrosine kinase, in healthy volunteers. Br J Clin Pharmacol. 2017 Nov;83(11):2367-2376. DOI:10.1111/bcp.13351
[2] Hill RJ, Bradshaw JM, Bisconte A, Tam D, Owens TD, Brameld KA, Smith PF, Funk JO, Goldstein DM, Nunn PA. Preclinical Characterization of PRN1008, a Novel Reversible Covalent Inhibitor of BTK that Shows Efficacy in a RAT Model of Collagen-Induced Arthritis. Annals of the Rheumatic Diseases 2015; 74(Suppl 2): 216.