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
PubMed
| Title | Date | PubMed |
|---|---|---|
| R406, an orally available spleen tyrosine kinase inhibitor blocks fc receptor signaling and reduces immune complex-mediated inflammation. | 2006 Dec |
|
| B-cell antigen receptor signaling enhances chronic lymphocytic leukemia cell migration and survival: specific targeting with a novel spleen tyrosine kinase inhibitor, R406. | 2009 Jul 30 |
Patents
Sample Use Guides
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
| Substance Class |
Chemical
Created
by
admin
on
Edited
Sat Dec 16 10:58:25 UTC 2023
by
admin
on
Sat Dec 16 10:58:25 UTC 2023
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| Record UNII |
RC3A285J2G
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| Record Status |
Validated (UNII)
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| Code System | Code | Type | Description | ||
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R-406
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11213558
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DB07159
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DTXSID30458939
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RC3A285J2G
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CHEMBL475251
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841290-80-0
Created by
admin on Sat Dec 16 10:58:26 UTC 2023 , Edited by admin on Sat Dec 16 10:58:26 UTC 2023
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| Related Record | Type | Details | ||
|---|---|---|---|---|
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TRANSPORTER -> SUBSTRATE | |||
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TARGET -> INHIBITOR |
R406 bound to the ATP binding pocket of Syk and inhibited its kinase activity as an ATP-competitive inhibitor.
COMPETITIVE INHIBITOR
Ki
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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 |
inhibited its kinase activity as an ATP-competitive inhibitor (Ki = 30 nM)
COMPETITIVE INHIBITOR
Ki
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| 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 |
