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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
Structure of R-406

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)

HIDE SMILES / InChI

Molecular Formula C22H23FN6O5
Molecular Weight 470.4536
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

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

Targets

Targets

Primary TargetPharmacologyConditionPotency
30.0 nM [Ki]
Conditions
PubMed

PubMed

TitleDatePubMed
Patents

Sample Use Guides

In Vivo Use Guide
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
BCR triggering increases CLL cell viability, and 5 uM R406 abrogates BCR-derived survival signals
Substance Class Chemical
Created
by admin
on Tue Oct 22 02:43:40 UTC 2019
Edited
by admin
on Tue Oct 22 02:43:40 UTC 2019
Record UNII
RC3A285J2G
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
R-406
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
TAMATINIB
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 Tue Oct 22 02:43:40 UTC 2019 , Edited by admin on Tue Oct 22 02:43:40 UTC 2019
PRIMARY
ChEMBL
CHEMBL475251
Created by admin on Tue Oct 22 02:43:40 UTC 2019 , Edited by admin on Tue Oct 22 02:43:40 UTC 2019
PRIMARY
CAS
841290-80-0
Created by admin on Tue Oct 22 02:43:40 UTC 2019 , Edited by admin on Tue Oct 22 02:43:40 UTC 2019
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
R406 bound to the ATP binding pocket of Syk and inhibited its kinase activity as an ATP-competitive inhibitor.
COMPETITIVE INHIBITOR
Ki
TARGET -> INHIBITOR
inhibited its kinase activity as an ATP-competitive inhibitor (Ki = 30 nM)
COMPETITIVE INHIBITOR
Ki
TRANSPORTER -> SUBSTRATE
METABOLIC ENZYME -> INHIBITOR
METABOLIC ENZYME -> INHIBITOR
METABOLIC ENZYME -> INDUCER
METABOLIC ENZYME -> INHIBITOR
Related Record Type Details
PRODRUG -> METABOLITE ACTIVE
Related Record Type Details
ACTIVE MOIETY