Tirabrutinib

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C25H22N6O3
Molecular Weight	454.4806
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC#CC(=O)N1CC[C@H](C1)N2C(=O)N(C3=C(N)N=CN=C23)C4=CC=C(OC5=CC=CC=C5)C=C4

InChI

InChIKey=SEJLPXCPMNSRAM-GOSISDBHSA-N

InChI=1S/C25H22N6O3/c1-2-6-21(32)29-14-13-18(15-29)31-24-22(23(26)27-16-28-24)30(25(31)33)17-9-11-20(12-10-17)34-19-7-4-3-5-8-19/h3-5,7-12,16,18H,13-15H2,1H3,(H2,26,27,28)/t18-/m1/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/30815927 | https://adisinsight.springer.com/drugs/800036049 | https://clinicaltrials.gov/ct2/show/NCT02983617 | https://clinicaltrials.gov/ct2/show/NCT03100942 | https://rctportal.niph.go.jp/en/detail?trial_id=JapicCTI-184231

Tirabrutinib (also known as ONO-4059 or GS-4059), a second-generation, enhanced-selectivity Bruton's tyrosine kinase inhibitor that demonstrated antitumor activity in preclinical models. Tirabrutinib participated in phase I clinical trial in patients with relapsed or refractory B-cell malignancies, where it was well tolerated and showed promising efficacy. In addition, tirabrutinib is involved in phase II clinical trials to study safety and efficacy in adults with Active Sjogren's syndrome and in adults with chronic lymphocytic leukemia. Besides the drug was studied for the treatment of Waldenstrom's macroglobulinemia and patients with refractory pemphigus.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Tyrosine-protein kinase BTK 24 Target ID: CHEMBL5251 Sources: https://www.ncbi.nlm.nih.gov/pubmed/29457982	Inhibitor 8297		11.0 nM [IC50]
Tyrosine-protein kinase BTK 24 Target ID: CHEMBL5251 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23958373	Inhibitor 8297		2.2 nM [IC50]

PubMed

Title	Date	PubMed
Ibrutinib and novel BTK inhibitors in clinical development.	2013 Aug 19	23958373
A phase 1 clinical trial of the selective BTK inhibitor ONO/GS-4059 in relapsed and refractory mature B-cell malignancies.	2016 Jan 28	26542378
Phase I study of tirabrutinib (ONO-4059/GS-4059) in patients with relapsed or refractory B-cell malignancies in Japan.	2019 May	30815927

Sample Use Guides

In Vivo Use Guide

40 mg tablet administered orally once daily

Route of Administration: Oral

Name

Type

Language

Tirabrutinib

Official Name

English

6-amino-9-[(3R)-1-(but-2-ynoyl)pyrrolidin-3-yl]-7-(4-phenoxyphenyl)-7,9-dihydro-8H-purin-8-one

Systematic Name

English

GS-4059

Code

English

TIRABRUTINIB [USAN]

Common Name

English

8H-Purin-8-one, 6-amino-7,9-dihydro-9-[(3R)-1-(1-oxo-2-butyn-1-yl)-3-pyrrolidinyl]-7-(4-phenoxyphenyl)-

Systematic Name

English

tirabrutinib [INN]

Common Name

English

ONO-4059(FREE BASE)

Code

English

Tirabrutinib [WHO-DD]

Common Name

English

ONO-4059

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C124801