Tirabrutinib Hydrochloride

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C25H22N6O3.ClH
Molecular Weight	490.942
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cl.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=UQYDCIJFACDXSG-GMUIIQOCSA-N

InChI=1S/C25H22N6O3.ClH/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);1H/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
PI3Kδ inhibitor idelalisib in combination with BTK inhibitor ONO/GS-4059 in diffuse large B cell lymphoma with acquired resistance to PI3Kδ and BTK inhibitors.	2017	28178345
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 Hydrochloride

Official Name

English

GS-4059 HYDROCHLORIDE

Code

English

Tirabrutinib hydrochloride [WHO-DD]

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)-, hydrochloride (1:1)

Systematic Name

English

ONO-4059 HYDROCHLORIDE

Code

English

TIRABRUTINIB HYDROCHLORIDE [JAN]

Common Name

English

TIRABRUTINIB HYDROCHLORIDE [USAN]

Common Name

English

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

Systematic Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

571116