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Details

Stereochemistry ABSOLUTE
Molecular Formula C27H29N5O3
Molecular Weight 471.5509
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ZANUBRUTINIB

SMILES

NC(=O)C1=C2NCC[C@@H](C3CCN(CC3)C(=O)C=C)N2N=C1C4=CC=C(OC5=CC=CC=C5)C=C4

InChI

InChIKey=RNOAOAWBMHREKO-QFIPXVFZSA-N
InChI=1S/C27H29N5O3/c1-2-23(33)31-16-13-18(14-17-31)22-12-15-29-27-24(26(28)34)25(30-32(22)27)19-8-10-21(11-9-19)35-20-6-4-3-5-7-20/h2-11,18,22,29H,1,12-17H2,(H2,28,34)/t22-/m0/s1

HIDE SMILES / InChI

Molecular Formula C27H29N5O3
Molecular Weight 471.5509
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Description

BGB-3111 is a potent and highly selective small molecule BTK inhibitor (Bruton’s Tyrosine Kinase), which we are developing as a monotherapy and in combination with other therapies for the treatment of a variety of lymphomas—the most common form of blood cancer. BGB-3111 blocks the signaling that leads to growth inhibition and cell death in malignant B-cells. In preclinical studies, BGB-3111 showed more restricted off-target activities against a panel of kinases, including ITK. Due to the weaker activity on ITK, BGB-3111 was at least 10 times weaker than ibrutinib in inhibiting rituximab-induced ADCC activity. Both in the REC-1 MCL and ABC subtype DLBCL (TMD-8) xenograft models, BGB-3111 induced dose-dependent antitumor effects and demonstrated superior efficacy in comparison with ibrutinib. Toxicity study in rats indicated that BGB-3111 was very well tolerated, and the MTD was not reached when it was dosed up to 250 mg/ kg/day. The first-in-human, open-label phase 1 trial of BGB-3111 is ongoing as a modified 3 + 3 dose-escalation design (40, 80, 160, 320 mg PO QD; 160 mg PO BID) in patients with advanced B cell malignancies.

Originator

Approval Year

PubMed

PubMed

TitleDatePubMed
Bruton tyrosine kinase inhibitor ONO/GS-4059: from bench to bedside.
2017 Jan 24
Patents

Patents

Sample Use Guides

In Vivo Use Guide
160mg PO BID
Route of Administration: Oral
In Vitro Use Guide
Ramos cells were serum starved in 0.5% FBS-containing RPMI1640 for 2 hours. Following starvation, the cells were incubated with compounds to be detected at various concentrations in a C02 incubator for 1 hour. After incubation, cells were stimulated with ImM pervanadate (PV) or Na3VC>4 (OV) for 20 min. Then, the cells were spinned down and lysed with lx lysis buffer at RT for 10 min (4x lysis buffer supplied in the kit). During the incubation, lx antibody mix was prepared by diluting anti-Btk-d2 and anti-pBtk-K in detection buffer (supplied in the kit). 2 ul/well of 1 x antibody mixture was dispensed into the OptiPlate-384 assay plate (6005620, Perkin Elmer). After that, 18 ul of cell lysate was transferred to the assay plate pre-loaded with antibody solution. After mixing gently and spinning briefly, the plate was sealed up and kept in dark at RT for 18 hours. The fluorescence emission was measured at two different wavelengths (665 nm and 620 nm) on a compatible HTRF reader (PHERAstar FS, BMG). The potency of compounds was calculated basing on the inhibition of ratio between signal intensities at 665nm and 620nm.
Substance Class Chemical
Created
by admin
on Mon Oct 21 20:09:52 UTC 2019
Edited
by admin
on Mon Oct 21 20:09:52 UTC 2019
Record UNII
AG9MHG098Z
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ZANUBRUTINIB
INN   USAN  
Official Name English
ZANUBRUTINIB [WHO-DD]
Common Name English
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)-
Systematic Name English
ZANUBRUTINIB [USAN]
Common Name English
BGB-3111
Code English
(7S)-2-(4-PHENOXYPHENYL)-7-(1-(PROP-2-ENOYL)PIPERIDIN-4-YL)-4,5,6,7-TETRAHYDROPYRAZOLO(1,5-A)PYRIMIDINE-3-CARBOXAMIDE
Systematic Name English
ZANUBRUTINIB [INN]
Common Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 527616
Created by admin on Mon Oct 21 20:09:52 UTC 2019 , Edited by admin on Mon Oct 21 20:09:52 UTC 2019
EU-Orphan Drug EU/3/19/2167
Created by admin on Mon Oct 21 20:09:52 UTC 2019 , Edited by admin on Mon Oct 21 20:09:52 UTC 2019
FDA ORPHAN DRUG 527516
Created by admin on Mon Oct 21 20:09:52 UTC 2019 , Edited by admin on Mon Oct 21 20:09:52 UTC 2019
NCI_THESAURUS C124801
Created by admin on Mon Oct 21 20:09:52 UTC 2019 , Edited by admin on Mon Oct 21 20:09:52 UTC 2019
NCI_THESAURUS C129825
Created by admin on Mon Oct 21 20:09:52 UTC 2019 , Edited by admin on Mon Oct 21 20:09:52 UTC 2019
FDA ORPHAN DRUG 527416
Created by admin on Mon Oct 21 20:09:52 UTC 2019 , Edited by admin on Mon Oct 21 20:09:52 UTC 2019
Code System Code Type Description
CAS
1691249-45-2
Created by admin on Mon Oct 21 20:09:52 UTC 2019 , Edited by admin on Mon Oct 21 20:09:52 UTC 2019
PRIMARY
NCI_THESAURUS
C141428
Created by admin on Mon Oct 21 20:09:52 UTC 2019 , Edited by admin on Mon Oct 21 20:09:52 UTC 2019
PRIMARY
PUBCHEM
135565884
Created by admin on Mon Oct 21 20:09:52 UTC 2019 , Edited by admin on Mon Oct 21 20:09:52 UTC 2019
PRIMARY
CAS
1651179-04-2
Created by admin on Mon Oct 21 20:09:52 UTC 2019 , Edited by admin on Mon Oct 21 20:09:52 UTC 2019
NO STRUCTURE GIVEN
INN
10555
Created by admin on Mon Oct 21 20:09:52 UTC 2019 , Edited by admin on Mon Oct 21 20:09:52 UTC 2019
PRIMARY
EVMPD
SUB195236
Created by admin on Mon Oct 21 20:09:52 UTC 2019 , Edited by admin on Mon Oct 21 20:09:52 UTC 2019
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
IRREVERSIBLE INHIBITOR
Related Record Type Details
ACTIVE MOIETY