Tirabrutinib Hydrochloride

Investigational

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

Molecular Formula	ClH
Molecular Weight	36.461
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	C25H22N6O3
Molecular Weight	454.4806
Charge	0
Count

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

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/23958373	Inhibitor 8504		2.2 nM [IC50]

C_max

Value	Dose	Analyte	Population
611 ng/mL OTHER GOV'T https://www.pmda.go.jp/files/000237315.pdf	160 mg single, oral dose: 160 mg route of administration: Oral experiment type: SINGLE co-administered:	TIRABRUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED
484 ng/mL OTHER GOV'T https://www.pmda.go.jp/files/000237315.pdf	160 mg 1 times / day multiple, oral dose: 160 mg route of administration: Oral experiment type: MULTIPLE co-administered:	TIRABRUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED
971 ng/mL OTHER GOV'T https://www.pmda.go.jp/files/000237315.pdf	320 mg 1 times / day multiple, oral dose: 320 mg route of administration: Oral experiment type: MULTIPLE co-administered:	TIRABRUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED
1220 ng/mL OTHER GOV'T https://www.pmda.go.jp/files/000237315.pdf	320 mg single, oral dose: 320 mg route of administration: Oral experiment type: SINGLE co-administered:	TIRABRUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED
1280 ng/mL OTHER GOV'T https://www.pmda.go.jp/files/000237315.pdf	480 mg single, oral dose: 480 mg route of administration: Oral experiment type: SINGLE co-administered:	TIRABRUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED
1940 ng/mL OTHER GOV'T https://www.pmda.go.jp/files/000237315.pdf	480 mg 1 times / day multiple, oral dose: 480 mg route of administration: Oral experiment type: MULTIPLE co-administered:	TIRABRUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED
961 ng/mL OTHER GOV'T https://www.pmda.go.jp/files/000237315.pdf	300 mg 2 times / day multiple, oral dose: 300 mg route of administration: Oral experiment type: MULTIPLE co-administered:	TIRABRUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED
886 ng/mL OTHER GOV'T https://www.pmda.go.jp/files/000237315.pdf	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	TIRABRUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED
2109 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32583848/	480 mg 1 times / day multiple, oral dose: 480 mg route of administration: Oral experiment type: MULTIPLE co-administered:	TIRABRUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
2860 ng × h/mL OTHER GOV'T https://www.pmda.go.jp/files/000237315.pdf	160 mg single, oral dose: 160 mg route of administration: Oral experiment type: SINGLE co-administered:	TIRABRUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED
2590 ng × h/mL OTHER GOV'T https://www.pmda.go.jp/files/000237315.pdf	160 mg 1 times / day multiple, oral dose: 160 mg route of administration: Oral experiment type: MULTIPLE co-administered:	TIRABRUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED
5370 ng × h/mL OTHER GOV'T https://www.pmda.go.jp/files/000237315.pdf	320 mg 1 times / day multiple, oral dose: 320 mg route of administration: Oral experiment type: MULTIPLE co-administered:	TIRABRUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED
4960 ng × h/mL OTHER GOV'T https://www.pmda.go.jp/files/000237315.pdf	320 mg single, oral dose: 320 mg route of administration: Oral experiment type: SINGLE co-administered:	TIRABRUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED
6790 ng × h/mL OTHER GOV'T https://www.pmda.go.jp/files/000237315.pdf	480 mg single, oral dose: 480 mg route of administration: Oral experiment type: SINGLE co-administered:	TIRABRUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED
12100 ng × h/mL OTHER GOV'T https://www.pmda.go.jp/files/000237315.pdf	480 mg 1 times / day multiple, oral dose: 480 mg route of administration: Oral experiment type: MULTIPLE co-administered:	TIRABRUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED
5510 ng × h/mL OTHER GOV'T https://www.pmda.go.jp/files/000237315.pdf	300 mg 2 times / day multiple, oral dose: 300 mg route of administration: Oral experiment type: MULTIPLE co-administered:	TIRABRUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED
4750 ng × h/mL OTHER GOV'T https://www.pmda.go.jp/files/000237315.pdf	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	TIRABRUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED
12315 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32583848/	480 mg 1 times / day multiple, oral dose: 480 mg route of administration: Oral experiment type: MULTIPLE co-administered:	TIRABRUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
4.96 h OTHER GOV'T https://www.pmda.go.jp/files/000237315.pdf	160 mg single, oral dose: 160 mg route of administration: Oral experiment type: SINGLE co-administered:	TIRABRUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED
4.52 h OTHER GOV'T https://www.pmda.go.jp/files/000237315.pdf	160 mg 1 times / day multiple, oral dose: 160 mg route of administration: Oral experiment type: MULTIPLE co-administered:	TIRABRUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED
4.47 h OTHER GOV'T https://www.pmda.go.jp/files/000237315.pdf	320 mg 1 times / day multiple, oral dose: 320 mg route of administration: Oral experiment type: MULTIPLE co-administered:	TIRABRUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED
4.92 h OTHER GOV'T https://www.pmda.go.jp/files/000237315.pdf	320 mg single, oral dose: 320 mg route of administration: Oral experiment type: SINGLE co-administered:	TIRABRUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED
6.38 h OTHER GOV'T https://www.pmda.go.jp/files/000237315.pdf	480 mg single, oral dose: 480 mg route of administration: Oral experiment type: SINGLE co-administered:	TIRABRUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED
3.07 h OTHER GOV'T https://www.pmda.go.jp/files/000237315.pdf	480 mg 1 times / day multiple, oral dose: 480 mg route of administration: Oral experiment type: MULTIPLE co-administered:	TIRABRUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED
5.79 h OTHER GOV'T https://www.pmda.go.jp/files/000237315.pdf	300 mg 2 times / day multiple, oral dose: 300 mg route of administration: Oral experiment type: MULTIPLE co-administered:	TIRABRUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED
4.37 h OTHER GOV'T https://www.pmda.go.jp/files/000237315.pdf	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	TIRABRUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED
3.3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32583848/	480 mg 1 times / day multiple, oral dose: 480 mg route of administration: Oral experiment type: MULTIPLE co-administered:	TIRABRUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
8.3% OTHER GOV'T https://www.pmda.go.jp/files/000237315.pdf	unknown, unknown		TIRABRUTINIB plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

PubMed

Title	Date	PubMed
Phase I study of tirabrutinib (ONO-4059/GS-4059) in patients with relapsed or refractory B-cell malignancies in Japan.	2019-05	30815927
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
A phase 1 clinical trial of the selective BTK inhibitor ONO/GS-4059 in relapsed and refractory mature B-cell malignancies.	2016-01-28	26542378
Ibrutinib and novel BTK inhibitors in clinical development.	2013-08-19	23958373

Sample Use Guides

In Vivo Use Guide

40 mg tablet administered orally once daily

Route of Administration: Oral

Substance Class	Chemical Created by `admin` on `Mon Mar 31 22:47:32 GMT 2025` Edited by `admin` on `Mon Mar 31 22:47:32 GMT 2025`
Record UNII	U374135N48
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

Tirabrutinib Hydrochloride

Official Name

English

ONO-4059 HYDROCHLORIDE

Preferred 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

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