| Identification | Back Directory | [Name]
Fostamatinib | [CAS]
901119-35-5 | [Synonyms]
R788
RT788
CS-883
R788 5MG
R-935788
R7935788
NSC-745942
R788, >=99%
Fostamatinib
R788 free base
R 788;R-788;R788
FostaMatinib (R788)
FostaMatinib DisodiuM
Fostamatinib USP/EP/BP
FOSTAMATINIB (R788);R788
R788 (Fostamatinib, FosD, tamatinib fosdium)
[6-[[5-fluoro-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]amino]-2,2-dimethyl-3-oxopyrido[3,2-b][1,4]oxazin-4-yl]methyl dihydrogen phosphate
6-[[5-Fluoro-2-[(3,4,5-trimethoxyphenyl)amino]-4-pyrimidinyl]amino]-2,2-dimethyl-4-[(phosphonooxy)methyl]-2H-pyrido[3,2-b]-1,4-oxazin-3(4H)-one
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-4-[(phosphonooxy)methyl]-
(6-(5-fluoro-2-(3,4,5-trimethoxyphenylamino)pyrimidin-4-ylamino)-2,2-dimethyl-3-oxo-2,3-dihydropyrido[3,2-b][1,4]oxazin-4-yl)methyl dihydrogen phosphate | [EINECS(EC#)]
618-473-2 | [Molecular Formula]
C23H26FN6O9P | [MDL Number]
MFCD16628163 | [MOL File]
901119-35-5.mol | [Molecular Weight]
580.46 |
| Chemical Properties | Back Directory | [Melting point ]
214° - 217°C | [Boiling point ]
814.2±75.0 °C(Predicted) | [density ]
1.496 | [storage temp. ]
-20°C, Hygroscopic | [solubility ]
DMSO (Slightly), Methanol (Slightly) | [form ]
Solid | [pka]
1.70±0.10(Predicted) | [color ]
White to Off-White | [Stability:]
Hygroscopic |
| Hazard Information | Back Directory | [Uses]
Fostamatinib can be used to treat cancers that have acquired resistance to kinase inhibitors. | [Indications]
Fostamatinib is an FDA-approved first-in-class spleen tyrosine kinase (SYK) inhibitor, specifically indicated for the treatment of adult patients with chronic immune thrombocytopenia (ITP) who have not responded adequately to prior therapies. | [Brand name]
Tavalisse | [General Description]
Class: non-receptor tyrosine kinase;
Treatment: ITP;
Other name: R788;
Oral bioavailability = 100% (prodrug);
Elimination half-life = 15 h (tamatinib);
Protein binding = 98.3% | [Biological Activity]
fostamatinib is a small molecule inhibitor of spleen tyrosine kinase (syk) with ic50 value of 41nm [1].fostamatinib is an orally bioavailable prodrug of r406. it is developed for the treatment of autoimmune diseases. the effective metabolite of fostamatinib, r406, is an atp-competitive inhibitor of syk with ki value of 30nm. r406 also inhibits the activity of other kinases including flt3, lyn (ic50=63nm) and lck (ic50=37nm). it is found that r406 inhibits both bcr and fcr mediated responses in vitro. besides that, r406 also shows effects in other cells types and signalling pathways. in the in vivo assay, fostamatinib shows to be highly active to inhibit fcr-mediated signaling in various animal models of allergy, autoimmunity and inflammation. moreover, fostamatinib also exerts efficacy in sle animal models. treatment of fostamatinib suppresses the established renal and skin disease and reduces lymphadenopathy in the mrl/lpr strain [1]. | [target]
Primary target: SYK | [References]
[1] mcadoo s p, tam f w k. fostamatinib disodium. drugs of the future, 2011, 36(4): 273. |
| Questions And Answer | Back Directory | [Binding Mode]
As shown in the co-crystal structure of
tamatinib-SYK (Fig. 1), the aminopyrimidine moiety
forms two hydrogen bonds with Ala451 of the hinge
region. In addition, there is an atypical hydrogen bond (CH...O=C) between CH at 6 and amide
carbonyl of Glu449 (Fig. 2).
  |
|
|