Identification | Back Directory | [Name]
Zanubrutinib | [CAS]
1691249-45-2 | [Synonyms]
anubrutinib Zanubrutinib The BTK inhibitor BGB-3111(Zanubrutinib) Zanubrutinib (BGB-3111) BGB-3111;ZANUBRUTINIB;BGB 3111;BGB3111 (S)-7-(1-Acryloylpiperidin-4-yl)-2-(4-phenoxyphenyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide Pyrazolo[1,5-a]pyrimidine-3-carboxamide, 4,5,6,7-tetrahydro-7-[1-(1-oxo-2-propen-1-yl)-4-piperidinyl]-2-(4-phenoxyphenyl)-, (7S)- | [Molecular Formula]
C27H29N5O3 | [MDL Number]
MFCD31567461 | [MOL File]
1691249-45-2.mol | [Molecular Weight]
471.55 |
Chemical Properties | Back Directory | [Boiling point ]
713.4±60.0 °C(Predicted) | [density ]
1.33±0.1 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMSO:99.67(Max Conc. mg/mL);211.36(Max Conc. mM) DMF:10.0(Max Conc. mg/mL);21.21(Max Conc. mM) DMF:PBS (pH 7.2) (1:5):0.16(Max Conc. mg/mL);0.34(Max Conc. mM) Ethanol:33.33(Max Conc. mg/mL);70.68(Max Conc. mM) | [form ]
A solid | [pka]
15.35±0.40(Predicted) |
Questions And Answer | Back Directory | [Binding Mode]
The electron density map corresponding to zanubrutinib and Cys481 showed covalent linkage with Cys481. Zanubrutinib forms three critical hydrogen bonds with hinge residues Glu475 and Met477. Compared with the co-crystal structure of ibrutinib with BTK, there is an additional hydrogen bond between the backbone carbonyl oxygen of Met477 and the 4-NH. The terminal phenyl group engages in a T-shape π–π stacking with Phe540, and the pyrazolyl nitrogen interacts with Lys430 via a water bridge. The warhead carbonyl also interacts indirectly with the amide NH of Asn484 via two water molecules. Both zanubrutinib and ibrutinib have a piperidinyl linker; however, they adopt two different binding modes in complex with BTK. In addition, a single crystal X-ray structure of zanubrutinib showed a classic intramolecular H-bond between carboxamide oxygen and the 4-NH, which confirmed the bioisosteric mimicry of the aminopyrimidine ring. |
Hazard Information | Back Directory | [Uses]
Zanubrutinib is classified as a Bruton''s tyrosine kinase inhibitor. Zanubrutinib is a medication for the treatment of adults with mantle cell lymphoma. |
|
|