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
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
| 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 |
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
Cmax
| Value | Dose | Co-administered | 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 | Co-administered | 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 |
T1/2
| Value | Dose | Co-administered | 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 |
Funbound
| 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 |
|
| 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 |
|
| A phase 1 clinical trial of the selective BTK inhibitor ONO/GS-4059 in relapsed and refractory mature B-cell malignancies. | 2016-01-28 |
|
| Ibrutinib and novel BTK inhibitors in clinical development. | 2013-08-19 |
| Substance Class |
Chemical
Created
by
admin
on
Edited
Mon Mar 31 22:47:32 GMT 2025
by
admin
on
Mon Mar 31 22:47:32 GMT 2025
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| Record UNII |
LXG44NDL2T
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| Record Status |
Validated (UNII)
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| Record Version |
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Official Name | English | ||
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Systematic Name | English | ||
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Systematic Name | English | ||
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Code | English | ||
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Common Name | English | ||
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Code | English |
| Classification Tree | Code System | Code | ||
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NCI_THESAURUS |
C124801
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FDA ORPHAN DRUG |
930322
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admin on Mon Mar 31 22:47:32 GMT 2025 , Edited by admin on Mon Mar 31 22:47:32 GMT 2025
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NCI_THESAURUS |
C129825
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| Code System | Code | Type | Description | ||
|---|---|---|---|---|---|
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LXG44NDL2T
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PRIMARY | |||
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100000172855
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C102876
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Tirabrutinib
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10320
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TIRABRUTINIB
Created by
admin on Mon Mar 31 22:47:32 GMT 2025 , Edited by admin on Mon Mar 31 22:47:32 GMT 2025
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PRIMARY | MedKoo CAT NO.: 205914, CAS NO.: 1351635-67-0Description: ONO4059-Analog, CAS#1351635-67-0, is a potent and selective BTK inhibitor, and is a structural analogue of ONO-4059. ONO4059 is currently under clinical trials. Note: ONO4059 HCl has CAS#1439901-97-9, ONO4059 free base has CAS#1351636-18-4. (Last updated: 5/19/2016).Synonym: ONO4059-Analog, ONO 4059-Analog, ONO-4059-Analog, GS 4059-Analog, GS-4059-Analog, GS4059-Analog.IUPAC/Chemical Name: (S)-9-(1-acryloylpiperidin-3-yl)-6-amino-7-(4-phenoxyphenyl)-7,9-dihydro-8H-purin-8-one | ||
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1351636-18-4
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54755438
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LM-62
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DB15227
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CHEMBL3544928
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| Related Record | Type | Details | ||
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SALT/SOLVATE -> PARENT |
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TARGET -> INHIBITOR |
IRREVERSIBLE INHIBITOR
IC50
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| Related Record | Type | Details | ||
|---|---|---|---|---|
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ACTIVE MOIETY |
Drugs: GS 4059(Primary), Entospletinib, Idelalisib; Indication: B cell lymphoma; Focus: Adverse reactions, Therapeutic Use; Sponsor: Gilead Sciences; Most Recent Events: 26 Jun 2016 Planned number of patients changed from 320 to 338., 10 May 2016 Planned End Date changed from 1 Jun 2018 to 1 Jan 2019., 10 May 2016 Planned primary completion date changed from 1 Jun 2017 to 1 Dec 2018.
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