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Chemical Structure| 841290-81-1 Chemical Structure| 841290-81-1

Structure of R406
CAS No.: 841290-81-1

Chemical Structure| 841290-81-1

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R406 is an orally available and competitive Syk/FLT3 inhibitor for ATP binding with a Ki of 30 nM. It potently inhibits Syk kinase activity in vitro with an IC50 of 41 nM, measured at an ATP concentration corresponding to its Km value. R406 reduces immune complex-mediated inflammation and also inhibits Lyn (IC50 = 63 nM) and Lck (IC50 = 37 nM).

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Product Details of R406

CAS No. :841290-81-1
Formula : C28H29FN6O8S
M.W : 628.63
SMILES Code : COC1=C(C=C(C=C1OC)NC2=NC(NC3=NC(N4)=C(C=C3)OC(C)(C)C4=O)=C(C=N2)F)OC.OS(C5=CC=CC=C5)(=O)=O
MDL No. :MFCD18385012
InChI Key :UXDRJPYSTZHIOE-UHFFFAOYSA-N
Pubchem ID :11984591

Safety of R406

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Related Pathways of R406

RTK

Isoform Comparison

Biological Activity

Target
  • FLT3

  • Syk

    Syk, IC50:41 nM

In Vitro:

Cell Line
Concentration Treated Time Description References
Kidney tubular epithelial cell line (P cells) 200 nM 48 hours To evaluate the effect of R406 (active metabolite of Fostamatinib) on MUC1 protein levels. Results showed that R406 significantly reduced MUC1 abundance on the plasma membrane and increased its intracellular distribution. Cell Rep Med. 2020 Oct 29;1(8):100137.
Ly6Chigh monocytes 1 μM R406 16 hours Evaluate the effect of R406 on M-CSF stimulated monocyte to macrophage differentiation. Results showed R406 blocked the differentiation process. Basic Res Cardiol. 2016 Mar;111(2):20.
Bone marrow cells 0.1 μM and 1 μM R406 5 days Evaluate the effect of R406 on GM-CSF/IL-3 stimulated colony formation of bone marrow cells. Results showed R406 significantly reduced colony formation. Basic Res Cardiol. 2016 Mar;111(2):20.
Spleen B-cells from TCL1 Tg mice 2.5 μM 48 h Suppression of Foxm1 and Ccl3 expression, indicating that R406 regulates Foxm1 and Ccl3 expression through inhibition of BCR signaling Leukemia. 2015 Jun;29(6):1350-9.
Chronic Lymphocytic Leukemia cells 100 μM 1 h R406, as a SYK inhibitor, was used to study its effects on Chronic Lymphocytic Leukemia cells. The results showed that R406 could block the anti-apoptotic effects of LAG3-Fc on CLL cells. Haematologica. 2017 May;102(5):874-882.
B1-8 B cells 5 μM 60 min To study the effect of Syk inhibitor R406 on B cell activation, results showed that R406 completely blocked the dissociation of BCR oligomers. Elife. 2014 Jun 24;3:e02069.
CH12 cells 1.85μM 18 h R406 inhibits BCR signaling, reducing phosphorylated proteins (including pBTK), but pSYK remains unchanged. Immunity. 2023 Oct 10;56(10):2373-2387.e8.
I29 cells 1.85μM 18 h R406 inhibits BCR signaling, reducing phosphorylated proteins (including pBTK), but pSYK remains unchanged. Immunity. 2023 Oct 10;56(10):2373-2387.e8.
BV2 cells 1 mM 24 h Inhibition of SYK activity to alleviate neuroinflammation Neural Regen Res. 2024 Jun 1;19(6):1375-1384.
SKOV3 cells 2.5 µM 48 h Inhibited SYK autophosphorylation, reduced cell proliferation Cancer Cell. 2015 Jul 13;28(1):82-96.
SKOV3TR cells 2.5 µM Enhanced cytotoxicity when combined with paclitaxel Cancer Cell. 2015 Jul 13;28(1):82-96.
microglia 1 mM 24 h Inhibit SYK kinase, reduce inflammatory response Cell Death Dis. 2019 Jul 19;10(8):555.
U87 10 μM 48 h R406 had minimal inhibitory effect on U87 cells, with an IC50 greater than 1 mM. Cell Death Dis. 2019 May 1;10(5):358.
C17.2 10 μM 48 h R406 was non-toxic to C17.2 cells, even at a concentration of 10 μM. Cell Death Dis. 2019 May 1;10(5):358.
U251 10 μM 48 h R406 had minimal inhibitory effect on U251 cells, with an IC50 greater than 1 mM. Cell Death Dis. 2019 May 1;10(5):358.
GSC-1 1 μM 48 h R406 significantly inhibited the proliferation of GSC-1 cells, with an IC50 of 0.75 μM. Cell Death Dis. 2019 May 1;10(5):358.
GSC-2 1 μM 48 h R406 significantly inhibited the proliferation of GSC-2 cells, with an IC50 of 0.89 μM. Cell Death Dis. 2019 May 1;10(5):358.
Monocytes 2 mM 24 h To investigate the effects of R406 on red blood cell phagocytosis and TNF-α production. The results showed that R406 significantly reduced red blood cell phagocytosis and TNF-α production Haematologica. 2024 Feb 1;109(2):444-457.

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Mice K14-HPV16 transgenic mice Oral 2.0 g/kg/day Starting at 1 month of age, continuing to 4 months of age In K14-HPV16 mice, fostamatinib (R788) inhibited Syk kinase activity and effectively blocked progression from low-grade hyperplasia to high-grade dysplasia. Cancer Cell. 2014 Jun 16;25(6):809-821
C57BL/6J mice MPTP-induced Parkinson's disease model Intraperitoneal injection 5 mg/kg Once daily for 5 consecutive days Inhibition of SYK activity to alleviate neuroinflammation Neural Regen Res. 2024 Jun 1;19(6):1375-1384.
Nude mice SKOV3c.2 subcutaneous tumor model Intraperitoneal injection 6.5 mg/kg Every three days, multiple cycles Significantly reduced tumor weight when combined with paclitaxel Cancer Cell. 2015 Jul 13;28(1):82-96.
C57BL/6J mice Middle cerebral artery occlusion model Intraperitoneal injection 5 mg/kg Once daily for 3 consecutive days Inhibit SYK kinase, reduce inflammatory response and neuronal injury Cell Death Dis. 2019 Jul 19;10(8):555.
BALB/c-nu/nu mice Subcutaneous tumor model Intraperitoneal injection 20 mg/kg Daily, continuous treatment R406 significantly inhibited tumor growth initiated by GSC-1 cells, and the combination with TMZ showed enhanced efficacy. Cell Death Dis. 2019 May 1;10(5):358.

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

1.59mL

0.32mL

0.16mL

7.95mL

1.59mL

0.80mL

15.91mL

3.18mL

1.59mL

 

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