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Details

Stereochemistry ACHIRAL
Molecular Formula C22H23FN6O5
Molecular Weight 470.4545
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TAMATINIB

SMILES

CC1(C)C(=Nc2c(ccc(=Nc3c(cnc(Nc4cc(c(c(c4)OC)OC)OC)n3)F)[nH]2)O1)O

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)

HIDE SMILES / InChI

Molecular Formula C22H23FN6O5
Molecular Weight 470.4545
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.

Approval Year

PubMed

PubMed

TitleDatePubMed
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
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

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
BCR triggering increases CLL cell viability, and 5 uM R406 abrogates BCR-derived survival signals
Substance Class Chemical
Created
by admin
on Sat Jun 26 07:26:09 UTC 2021
Edited
by admin
on Sat Jun 26 07:26:09 UTC 2021
Record UNII
RC3A285J2G
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
TAMATINIB
Common Name English
R940406
Common Name English
2H-PYRIDO(3,2-B)-1,4-OXAZIN-3(4H)-ONE, 6-((5-FLUORO-2-((3,4,5-TRIMETHOXYPHENYL)AMINO)-4-PYRIMIDINYL)AMINO)-2,2-DIMETHYL-
Systematic Name English
R-406
Common Name English
6-(5-FLUORO-2-(3,4,5-TRIMETHOXY-PHENYLAMINO)-PYRIMIDIN-4-YLAMINO)-2,2-DIMETHYL-4H-PYRIDO(3,2-B)(1,4)OXAZIN-3-ONE
Systematic Name English
Code System Code Type Description
WIKIPEDIA
R-406
Created by admin on Sat Jun 26 07:26:09 UTC 2021 , Edited by admin on Sat Jun 26 07:26:09 UTC 2021
PRIMARY
PUBCHEM
11213558
Created by admin on Sat Jun 26 07:26:09 UTC 2021 , Edited by admin on Sat Jun 26 07:26:09 UTC 2021
PRIMARY
DRUG BANK
DB07159
Created by admin on Sat Jun 26 07:26:09 UTC 2021 , Edited by admin on Sat Jun 26 07:26:09 UTC 2021
PRIMARY
FDA UNII
RC3A285J2G
Created by admin on Sat Jun 26 07:26:09 UTC 2021 , Edited by admin on Sat Jun 26 07:26:09 UTC 2021
PRIMARY
ChEMBL
CHEMBL475251
Created by admin on Sat Jun 26 07:26:09 UTC 2021 , Edited by admin on Sat Jun 26 07:26:09 UTC 2021
PRIMARY
CAS
841290-80-0
Created by admin on Sat Jun 26 07:26:09 UTC 2021 , Edited by admin on Sat Jun 26 07:26:09 UTC 2021
PRIMARY
Related Record Type Details
TRANSPORTER -> SUBSTRATE
METABOLIC ENZYME -> INHIBITOR
TARGET -> INHIBITOR
R406 bound to the ATP binding pocket of Syk and inhibited its kinase activity as an ATP-competitive inhibitor.
COMPETITIVE INHIBITOR
Ki
METABOLIC ENZYME -> INHIBITOR
METABOLIC ENZYME -> INDUCER
METABOLIC ENZYME -> INHIBITOR
TARGET -> INHIBITOR
inhibited its kinase activity as an ATP-competitive inhibitor (Ki = 30 nM)
COMPETITIVE INHIBITOR
Ki
Related Record Type Details
METABOLITE -> PARENT
FECAL
METABOLITE -> PARENT
PLASMA
METABOLITE -> PARENT
PLASMA; URINE
METABOLITE -> PARENT
PLASMA
PRODRUG -> METABOLITE ACTIVE
METABOLITE -> PARENT
Related Record Type Details
ACTIVE MOIETY