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Details

Stereochemistry ABSOLUTE
Molecular Formula C27H29N5O3
Molecular Weight 471.5519
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ZANUBRUTINIB

SMILES

C=CC(=O)N1CCC(CC1)[C@]2([H])CCNc3c(c(-c4ccc(cc4)Oc5ccccc5)nn23)C(=O)N

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 471.5519
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Zanubrutinib (formerly known as BGB-3111) was developed by BeiGene as a small-molecule inhibitor of Bruton's tyrosine kinase (BTK). The drug forms a covalent bond with a cysteine residue in the BTK active site, leading to inhibition of BTK activity. BTK signaling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis, and adhesion, thus Zanubrutinib inhibits malignant B-cell proliferation and reduces tumor growth. Zanubrutinib was granted accelerated approval by the FDA in November 2019 based on clinical trial results that demonstrated an 84% overall response rate from zanubrutinib therapy in patients with mantle cell lymphoma (MCL). On August 31, 2021, the Food and Drug Administration approved zanubrutinib for adult patients with Waldenström’s macroglobulinemia (WM).

CNS Activity

Curator's Comment:: Zanubrutinib possesses an inferior ability to pass through BBB compared to ibrutinib and tirabrutinib.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: Q06187
Gene ID: 695.0
Gene Symbol: BTK
Target Organism: Homo sapiens (Human)
0.3 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
BRUKINSA

Approved Use

indicated for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy
Primary
Brukinsa

Approved Use

zanubrutinib (Brukinsa, BeiGene) for adult patients with Waldenström’s macroglobulinemia

Launch Date

1.63036804E12

Sample Use Guides

160 mg orally twice daily or 320 mg orally once daily; swallow whole with water and with or without food
Route of Administration: Oral
The in vitro cell-based activity of zanubrutinib on BTK was evaluated in mantle cell lymphoma (MCL) cell lines and showed that BTK was inhibited with an IC50 of 1.8 nM. In vitro activity was evaluated on a panel of 23 hematologic cancer cell lines. Zanubrutinib demonstrated the most prominent growth inhibitory activity on 3 MCL cell lines and a diffuse large B-cell lymphoma (DLBCL) cell line.
Substance Class Chemical
Created
by admin
on Sat Jun 26 03:59:40 UTC 2021
Edited
by admin
on Sat Jun 26 03:59:40 UTC 2021
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
BRUKINSA
Brand 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 [ORANGE BOOK]
Common Name English
ZANUBRUTINIB [INN]
Common Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 756920
Created by admin on Sat Jun 26 03:59:40 UTC 2021 , Edited by admin on Sat Jun 26 03:59:40 UTC 2021
FDA ORPHAN DRUG 527616
Created by admin on Sat Jun 26 03:59:40 UTC 2021 , Edited by admin on Sat Jun 26 03:59:40 UTC 2021
FDA ORPHAN DRUG 757020
Created by admin on Sat Jun 26 03:59:40 UTC 2021 , Edited by admin on Sat Jun 26 03:59:40 UTC 2021
FDA ORPHAN DRUG 757120
Created by admin on Sat Jun 26 03:59:40 UTC 2021 , Edited by admin on Sat Jun 26 03:59:40 UTC 2021
EU-Orphan Drug EU/3/19/2167
Created by admin on Sat Jun 26 03:59:40 UTC 2021 , Edited by admin on Sat Jun 26 03:59:40 UTC 2021
FDA ORPHAN DRUG 527516
Created by admin on Sat Jun 26 03:59:40 UTC 2021 , Edited by admin on Sat Jun 26 03:59:40 UTC 2021
NCI_THESAURUS C124801
Created by admin on Sat Jun 26 03:59:40 UTC 2021 , Edited by admin on Sat Jun 26 03:59:40 UTC 2021
NCI_THESAURUS C129825
Created by admin on Sat Jun 26 03:59:40 UTC 2021 , Edited by admin on Sat Jun 26 03:59:40 UTC 2021
FDA ORPHAN DRUG 527416
Created by admin on Sat Jun 26 03:59:40 UTC 2021 , Edited by admin on Sat Jun 26 03:59:40 UTC 2021
Code System Code Type Description
CAS
1691249-45-2
Created by admin on Sat Jun 26 03:59:40 UTC 2021 , Edited by admin on Sat Jun 26 03:59:40 UTC 2021
PRIMARY
RXCUI
2262435
Created by admin on Sat Jun 26 03:59:40 UTC 2021 , Edited by admin on Sat Jun 26 03:59:40 UTC 2021
PRIMARY
NCI_THESAURUS
C141428
Created by admin on Sat Jun 26 03:59:40 UTC 2021 , Edited by admin on Sat Jun 26 03:59:40 UTC 2021
PRIMARY
DRUG BANK
DB15035
Created by admin on Sat Jun 26 03:59:40 UTC 2021 , Edited by admin on Sat Jun 26 03:59:40 UTC 2021
PRIMARY
DRUG CENTRAL
5353
Created by admin on Sat Jun 26 03:59:40 UTC 2021 , Edited by admin on Sat Jun 26 03:59:40 UTC 2021
PRIMARY
PUBCHEM
135565884
Created by admin on Sat Jun 26 03:59:40 UTC 2021 , Edited by admin on Sat Jun 26 03:59:40 UTC 2021
PRIMARY
CAS
1651179-04-2
Created by admin on Sat Jun 26 03:59:40 UTC 2021 , Edited by admin on Sat Jun 26 03:59:40 UTC 2021
NO STRUCTURE GIVEN
FDA UNII
AG9MHG098Z
Created by admin on Sat Jun 26 03:59:40 UTC 2021 , Edited by admin on Sat Jun 26 03:59:40 UTC 2021
PRIMARY
INN
10555
Created by admin on Sat Jun 26 03:59:40 UTC 2021 , Edited by admin on Sat Jun 26 03:59:40 UTC 2021
PRIMARY
EVMPD
SUB195236
Created by admin on Sat Jun 26 03:59:40 UTC 2021 , Edited by admin on Sat Jun 26 03:59:40 UTC 2021
PRIMARY
Related Record Type Details
METABOLIC ENZYME -> INDUCER
Zanubrutinib is a weak inducer of CYP3A4 and CYP2C19 in vivo.
WEAK
EXCRETED UNCHANGED
URINE
BINDER->LIGAND
Zanubrutinib is approximately 94.2% bound to human plasma proteins in vitro, independent of concentration.
BINDING
EXCRETED UNCHANGED
FECAL
METABOLIC ENZYME -> INDUCER
Zanubrutinib induces CYP2B6 in vitro.
TARGET -> INHIBITOR
IRREVERSIBLE INHIBITOR
TRANSPORTER -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
MAJOR
TRANSPORTER -> INHIBITOR
METABOLIC ENZYME -> INDUCER
Zanubrutinib is a weak inducer of CYP3A4 and CYP2C19 in vivo.
WEAK
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
blood-to-plasma ratio PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC
Tmax PHARMACOKINETIC ORAL ADMINISTRATION

Volume of Distribution PHARMACOKINETIC