Details
Stereochemistry | ACHIRAL |
Molecular Formula | C22H23FN6O5 |
Molecular Weight | 470.4536 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
COC1=CC(NC2=NC=C(F)C(NC3=CC=C4OC(C)(C)C(=O)NC4=N3)=N2)=CC(OC)=C1OC
InChI
InChIKey=NHHQJBCNYHBUSI-UHFFFAOYSA-N
InChI=1S/C22H23FN6O5/c1-22(2)20(30)28-19-13(34-22)6-7-16(27-19)26-18-12(23)10-24-21(29-18)25-11-8-14(31-3)17(33-5)15(9-11)32-4/h6-10H,1-5H3,(H3,24,25,26,27,28,29,30)
Molecular Formula | C22H23FN6O5 |
Molecular Weight | 470.4536 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
R406 (TAMATINIB) is an ATP-competitive inhibitor of spleen tyrosine kinase (Syk), which plays a key role in the signaling of activating Fc receptors and the B-cell receptor (BCR). R406 blocked Syk-dependent FcR-mediated activation of monocytes/macrophages and neutrophils and BCR-mediated activation of B lymphocytes. R406 was selective as assessed using a large panel of Syk-independent cell-based assays representing both specific and general signaling pathways. Consistent with Syk inhibition, oral administration of R406 to mice reduced immune complex-mediated inflammation in a reverse-passive Arthus reaction and two antibody-induced arthritis models. R406 is the active compound of pro-drug Fostamatinib (R-788). Fostamatinib is being developed by Rigel Pharmaceuticals for the treatment of immune thrombocytopenic purpura (ITP) and IgA nephropathy.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL2599 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16946104 |
30.0 nM [Ki] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
|||
Primary | Unknown Approved UseUnknown |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
501 ng/mL |
80 mg single, oral dose: 80 mg route of administration: Oral experiment type: SINGLE co-administered: |
R406 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
2030 ng/mL |
250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered: |
R406 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
3410 ng/mL |
400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered: |
R406 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
3660 ng/mL |
500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered: |
R406 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
3920 ng/mL |
600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered: |
R406 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
306 ng/mL |
80 mg single, oral dose: 80 mg route of administration: Oral experiment type: SINGLE co-administered: |
R406 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
1140 ng/mL |
250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered: |
R406 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
1220 ng/mL |
400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered: |
R406 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
682 ng/mL |
100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered: |
R406 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
605 ng/mL |
75 mg single, oral dose: 75 mg route of administration: Oral experiment type: SINGLE co-administered: |
R406 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
363 ng/mL |
75 mg single, oral dose: 75 mg route of administration: Oral experiment type: SINGLE co-administered: |
R406 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
747 ng/mL |
160 mg 2 times / day multiple, oral dose: 160 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
R406 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
1530 ng/mL |
160 mg 2 times / day steady-state, oral dose: 160 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
R406 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
397 ng/mL |
100 mg 2 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
R406 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
761 ng/mL |
100 mg 2 times / day steady-state, oral dose: 100 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
R406 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
690 ng/mL |
150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered: |
R406 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
425 ng/mL |
150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered: |
R406 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
407 ng/mL |
150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered: |
R406 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
529 ng/mL |
150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered: |
R406 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
692 ng/mL |
150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered: |
R406 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
615 ng/mL |
150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered: |
R406 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
602 ng/mL |
150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered: |
R406 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
582 ng/mL |
150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered: |
R406 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
4410 ng × h/mL |
80 mg single, oral dose: 80 mg route of administration: Oral experiment type: SINGLE co-administered: |
R406 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
18100 ng × h/mL |
250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered: |
R406 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
34900 ng × h/mL |
400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered: |
R406 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
29600 ng × h/mL |
500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered: |
R406 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
36600 ng × h/mL |
600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered: |
R406 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
3150 ng × h/mL |
80 mg single, oral dose: 80 mg route of administration: Oral experiment type: SINGLE co-administered: |
R406 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
13700 ng × h/mL |
250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered: |
R406 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
13400 ng × h/mL |
400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered: |
R406 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
7510 ng × h/mL |
100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered: |
R406 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
6490 ng × h/mL |
75 mg single, oral dose: 75 mg route of administration: Oral experiment type: SINGLE co-administered: |
R406 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
7140 ng × h/mL |
75 mg single, oral dose: 75 mg route of administration: Oral experiment type: SINGLE co-administered: |
R406 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
8250 ng × h/mL |
160 mg 2 times / day multiple, oral dose: 160 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
R406 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
19900 ng × h/mL |
160 mg 2 times / day steady-state, oral dose: 160 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
R406 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
3260 ng × h/mL |
100 mg 2 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
R406 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
6750 ng × h/mL |
150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered: |
R406 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
6110 ng × h/mL |
150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered: |
R406 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
4950 ng × h/mL |
150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered: |
R406 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
6280 ng × h/mL |
150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered: |
R406 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
8970 ng × h/mL |
150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered: |
R406 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
6390 ng × h/mL |
150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered: |
R406 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
6860 ng × h/mL |
150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered: |
R406 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
9490 ng × h/mL |
150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered: |
R406 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
14.5 h |
80 mg single, oral dose: 80 mg route of administration: Oral experiment type: SINGLE co-administered: |
R406 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
14.9 h |
250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered: |
R406 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
17.8 h |
400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered: |
R406 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
20.9 h |
500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered: |
R406 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
12.9 h |
600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered: |
R406 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
14.8 h |
80 mg single, oral dose: 80 mg route of administration: Oral experiment type: SINGLE co-administered: |
R406 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
16 h |
250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered: |
R406 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
12.1 h |
400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered: |
R406 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
19 h |
100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered: |
R406 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
17.9 h |
75 mg single, oral dose: 75 mg route of administration: Oral experiment type: SINGLE co-administered: |
R406 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
18.4 h |
75 mg single, oral dose: 75 mg route of administration: Oral experiment type: SINGLE co-administered: |
R406 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
19.9 h |
160 mg 2 times / day multiple, oral dose: 160 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
R406 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
14.5 h |
100 mg 2 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
R406 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
20.4 h |
100 mg 2 times / day steady-state, oral dose: 100 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
R406 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
20.5 h |
150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered: |
R406 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
23.8 h |
150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered: |
R406 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
19.6 h |
150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered: |
R406 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
22.1 h |
150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered: |
R406 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
19.4 h |
150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered: |
R406 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
16.7 h |
150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered: |
R406 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
16.1 h |
150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered: |
R406 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
19.2 h |
150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered: |
R406 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
3.7% |
80 mg single, oral dose: 80 mg route of administration: Oral experiment type: SINGLE co-administered: |
R406 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
PubMed
Title | Date | PubMed |
---|---|---|
R406, an orally available spleen tyrosine kinase inhibitor blocks fc receptor signaling and reduces immune complex-mediated inflammation. | 2006 Dec |
|
The Syk-kinase inhibitor R406 impairs platelet activation and monocyte tissue factor expression triggered by heparin-PF4 complex directed antibodies. | 2011 Oct |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/16946104
Pharmacokinetic assessment indicated that R406 was highly bioavailable. R406 plasma concentration increased in a dose-proportional fashion up to 400 mg and then reached a plateau. The maximal R406 concentration was generally reached between 1.2 and 1.3 h after dosing, and the half-life was approximately 15 h.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/19491390
BCR triggering increases CLL cell viability, and 5 uM R406 abrogates BCR-derived survival signals
Substance Class |
Chemical
Created
by
admin
on
Edited
Mon Mar 31 23:32:51 GMT 2025
by
admin
on
Mon Mar 31 23:32:51 GMT 2025
|
Record UNII |
RC3A285J2G
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Record Status |
Validated (UNII)
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Record Version |
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-
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Name | Type | Language | ||
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Preferred Name | English | ||
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Common Name | English | ||
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Common Name | English | ||
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Systematic Name | English | ||
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Systematic Name | English |
Code System | Code | Type | Description | ||
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R-406
Created by
admin on Mon Mar 31 23:32:51 GMT 2025 , Edited by admin on Mon Mar 31 23:32:51 GMT 2025
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PRIMARY | |||
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11213558
Created by
admin on Mon Mar 31 23:32:51 GMT 2025 , Edited by admin on Mon Mar 31 23:32:51 GMT 2025
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PRIMARY | |||
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DB07159
Created by
admin on Mon Mar 31 23:32:51 GMT 2025 , Edited by admin on Mon Mar 31 23:32:51 GMT 2025
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PRIMARY | |||
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DTXSID30458939
Created by
admin on Mon Mar 31 23:32:51 GMT 2025 , Edited by admin on Mon Mar 31 23:32:51 GMT 2025
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PRIMARY | |||
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RC3A285J2G
Created by
admin on Mon Mar 31 23:32:51 GMT 2025 , Edited by admin on Mon Mar 31 23:32:51 GMT 2025
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PRIMARY | |||
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CHEMBL475251
Created by
admin on Mon Mar 31 23:32:51 GMT 2025 , Edited by admin on Mon Mar 31 23:32:51 GMT 2025
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PRIMARY | |||
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841290-80-0
Created by
admin on Mon Mar 31 23:32:51 GMT 2025 , Edited by admin on Mon Mar 31 23:32:51 GMT 2025
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PRIMARY |
Related Record | Type | Details | ||
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TARGET -> INHIBITOR | |||
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TRANSPORTER -> SUBSTRATE |
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METABOLIC ENZYME -> INHIBITOR | |||
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METABOLIC ENZYME -> INHIBITOR | |||
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METABOLIC ENZYME -> INDUCER | |||
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METABOLIC ENZYME -> INHIBITOR | |||
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TARGET -> INHIBITOR |
Related Record | Type | Details | ||
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METABOLITE -> PARENT |
FECAL
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METABOLITE -> PARENT |
PLASMA
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METABOLITE -> PARENT |
PLASMA; URINE
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METABOLITE -> PARENT |
PLASMA
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PRODRUG -> METABOLITE ACTIVE |
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METABOLITE -> PARENT |
Related Record | Type | Details | ||
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ACTIVE MOIETY |
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