R406 free base
Based on 37 publication(s) in Google Scholar
R406 free base is an orally available and competitive Syk/FLT3 inhibitor for ATP binding with a Ki of 30 nM, potently inhibits Syk kinase activity in vitro with an IC50 of 41 nM, measured at an ATP concentration corresponding to its Km value. R406 free base reduces immune complex-mediated inflammation. R406 free base also inhibits Lyn (IC50=63 nM) and Lck (IC50=37 nM).
For research use only. We do not sell to patients.
- Purity: 99.07%
- CAS No.: 841290-80-0
- Formula: C22H23FN6O5
- Molecular Weight:470.45
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Storage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year
Publications Citing Use of MedChemExpress (MCE) R406 free base
More- Nature. 2026 Jan;649(8098):1032-1041. [Abstract]
- Cell. 2018 Oct 4;175(2):442-457.e23. [Abstract]
- Adv Mater. 2024 Mar 15:e2311283. [Abstract]
- Nat Commun. 2022 Apr 19;13(1):2136. [Abstract]
- Sci Transl Med. 2018 Jul 18;10(450):eaaq1093. [Abstract]
- Exp Hematol Oncol. 2022 Nov 8;11(1):88. [Abstract]
- Theranostics. 2021 May 24;11(15):7308-7321. [Abstract]
- J Adv Res. 2026 Jan 22:S2090-1232(26)00069-X. [Abstract]
- Redox Biol. 2022 Oct:56:102461. [Abstract]
- Arthritis Rheumatol. 2018 Sep;70(9):1419-1428. [Abstract]
- Cell Rep Med. 2025 Jan 16:101922. [Abstract]
- Mater Today Bio. 2024 Mar 22:26:101037. [Abstract]
- J Neuroinflammation. 2024 Dec 3;21(1):318. [Abstract]
- Cell Death Dis. 2025 Aug 7;16(1):595. [Abstract]
- Cell Commun Signal. 2024 Apr 2;22(1):210. [Abstract]
- Blood Adv. 2024 Nov 12;8(21):5653-5662. [Abstract]
- Cell Rep. 2023 Mar 20;42(3):112275. [Abstract]
- Atherosclerosis. 2019 Oct;289:132-142. [Abstract]
- Front Pharmacol. 2022 May 5;13:885053. [Abstract]
- iScience. 2024 Jun 28;27(7):110415. [Abstract]
- iScience. 2024 Mar 27;27(4):109607. [Abstract]
- iScience. 2024 Jan 11;27(2):108869. [Abstract]
- J Biol Chem. 2018 Apr 27;293(17):6410-6433. [Abstract]
- ACS Infect Dis. 2026 Jun 25. [Abstract]
- ACS Infect Dis. 2021 Mar 12;7(3):661-671. [Abstract]
- Life Metab. 2025 Jan 29;4(2):loaf002. [Abstract]
- Mol Immunol. 2024 Jul 31:173:88-98. [Abstract]
- J Pharmacol Sci. 2017 May;134(1):29-36. [Abstract]
- BMC Cardiovasc Disord. 2024 Jul 12;24(1):354. [Abstract]
- Scand J Immunol. 2024 Apr 26:e13371. [Abstract]
- SSRN. 2025 Dec 2.
- Stony Brook University. 2025.
- bioRxiv. 2024 Apr 9.
- SSRN. 2023 Jun 29.
- bioRxiv. 2022 Dec 21, 519945.
- Ann Transl Med. 2019 Dec;7(23):758. [Abstract]
- Nihon University. School of Medicine. 2014 Mar.
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Cell Migration/Invasion Assay
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WB
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Flow Cytometry
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IP
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WB
Biological Activity
Ki: 30 nM (Syk)[1]
IC50: 41 nM (Syk)[1]
FLT3[1]
IC50: 63 nM (Lyn), 37 nM (Lck)[2]
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| B-cell | EC50 |
48 nM
Compound: 3, R406
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Inhibition of SYK in human B-cells cells assessed as reduction in FcepsilonR1/FcgammaR-mediated signaling responses
Inhibition of SYK in human B-cells cells assessed as reduction in FcepsilonR1/FcgammaR-mediated signaling responses
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[PMID: 22257213] |
| Bone marrow cell | IC50 |
147 nM
Compound: 2
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Inhibition of IL3 dependent proliferation in C57/B16 mouse bone marrow cells using [3H]thymidine by liquid scintillation counting
Inhibition of IL3 dependent proliferation in C57/B16 mouse bone marrow cells using [3H]thymidine by liquid scintillation counting
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[PMID: 24726806] |
| HUVEC | EC50 |
36 nM
Compound: 1, R406
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Inhibition of KDR in VEGF-stimulated HUVEC assessed as phosphorylation after 1 hr incubation
Inhibition of KDR in VEGF-stimulated HUVEC assessed as phosphorylation after 1 hr incubation
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[PMID: 24779514] |
| MV4-11 | EC50 |
10 nM
Compound: 1, R406
|
Inhibition of Flt3 in human MV411 cells assessed as assessed as proliferation after 72 hrs incubation by spectrophotometry
Inhibition of Flt3 in human MV411 cells assessed as assessed as proliferation after 72 hrs incubation by spectrophotometry
|
[PMID: 24779514] |
| Ramos | EC50 |
53 nM
Compound: 1, R406
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Inhibition of Syk in antihuman IgM-stimulated human Ramos cells assessed as decrease in BCR-mediated BLNK phosphorylation by cellular assay
Inhibition of Syk in antihuman IgM-stimulated human Ramos cells assessed as decrease in BCR-mediated BLNK phosphorylation by cellular assay
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[PMID: 24779514] |
| Ramos | IC50 |
457 nM
Compound: 2
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Inhibition of Syk in anti IgM-stimulated human Ramos cells assessed as BLNK phosphorylation by cellular assay
Inhibition of Syk in anti IgM-stimulated human Ramos cells assessed as BLNK phosphorylation by cellular assay
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[PMID: 24726806] |
| SK-N-SH | EC50 |
80 nM
Compound: 3, R406
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Inhibition of Ret in human SK-N-SH cells
Inhibition of Ret in human SK-N-SH cells
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[PMID: 22257213] |
| TF-1 | EC50 |
13 nM
Compound: 1, R406
|
Inhibition of Jak2 in erythropoietin-stimulated human TF1 cells assessed as assessed as phospho-Stat5 after 1 hr incubation
Inhibition of Jak2 in erythropoietin-stimulated human TF1 cells assessed as assessed as phospho-Stat5 after 1 hr incubation
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[PMID: 24779514] |
| THP-1 | EC50 |
171 nM
Compound: 3, R406
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Inhibition of SYK in human THP1 cells assessed as reduction in FcepsilonR1/FcgammaR-mediated signaling responses
Inhibition of SYK in human THP1 cells assessed as reduction in FcepsilonR1/FcgammaR-mediated signaling responses
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[PMID: 22257213] |
R406 inhibits adenosine A3 receptor (IC50=0.081 μM), adenosine transporter (IC50=1.84 μM), and monoamine transporter (IC50=2.74 μM)[1].
R406 inhibits Huh7 hepatocyte, A549 epithelial, and H1299 lung cancer lines with EC50s of 15.1, 2.9 and 6.3 μM, respectively[1].
R406 inhibits phosphorylation of Syk substrate LAT in mast cells and BLNK/SLP65 in B cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:Cultured human mast cells (CHMC)
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Concentration:0.016, 0.08, 0.4, 2 µM
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Incubation Time:40 minutes
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Result:Inhibited all other kinases tested at 5 to 100 fold less potency than Syk as judged by phosphorylation of target proteins.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Female Balb/c mice (6-8 weeks) with CAIA[1]
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Dosage:5 and 10 mg/kg
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Administration:Administered orally, b.i.d, for 14 days, starting 4 hours after antibody challenge on day 0.
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Result:Reduced inflammation and swelling, and the arthritis progressed more slowly in treated animals than in vehicle controls.
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Animal Model:Female C57BL/6 mice with arthritis[1]
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Dosage:10 mg/kg
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Administration:Administered orally one hour before serum injection; b.i.d; for 13 days
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Result:Delayed the onset and reduced the severity of clinical arthritis. Paw thickening and clinical arthritis were reduced by approximately 50%.
Chemical Information
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CAS No. 841290-80-0
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Appearance Solid
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Molecular Weight 470.45
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Formula C22H23FN6O5
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Color White to light yellow
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SMILES
COC1=CC(NC2=NC(NC3=NC(N4)=C(C=C3)OC(C)(C)C4=O)=C(C=N2)F)=CC(OC)=C1OC
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 2 years -20°C 1 year
Publications (37)
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Journal Impact Factor
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Most Recent
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Nature
2026 Jan;649(8098):1032-1041. PMID: 41299171 -
Cell
2018 Oct 4;175(2):442-457.e23. PMID: 30290143
R406 free base purchased from MedChemExpress. Usage Cited in: Cell. 2018 Oct 4;175(2):442-457.e23. [Abstract]
Syk inhibitors (R406 (5 μM) and Piceatannol) are added during the induction of trastuzumab-dependent BT-474 phagocytosis. The binding of the phagosome marker Rab7 to AIM2 in macrophages are evaluated by co-immunoprecipitation.
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Adv Mater
Glycocalyx-Mimicking Nanoparticles with Differential Organ Selectivity for Drug Delivery and Therapy. [Abstract]2024 Mar 15:e2311283. PMID: 38489768 -
Nat Commun
A loss-of-adhesion CRISPR-Cas9 screening platform to identify cell adhesion-regulatory proteins and signaling pathways. [Abstract]2022 Apr 19;13(1):2136. PMID: 35440579
R406 free base purchased from MedChemExpress. Usage Cited in: Nat Commun. 2022 Apr 19;13(1):2136. [Abstract]
Comparison of pharmacological inhibitors with the corresponding guides of positive and negative controls for BCR-controlled adhesion. Top plots: Namalwa cells pretreated with 100 nM ibrutinib (BTK inhibitor), 1 μM R406 (Fostamatinib, SYK inhibitor, 1 ), 100 nM wortmannin (pan-PI3K inhibitor), 50 μM PD-98059 (MEK1/2 inhibitor), 2.5 μM MK-2206 (AKT1/2/3 inhibitor), or DMSO control, were stimulated with αIgM or PMA, and allowed to adhere to fibronectin-coated surfaces. Bar graphs are presented as normalized mean + SEM (100% = untreated αIgM-stimulated cells). Bottom plots: MA plots of αIgM-induced adhesion relative to PMA-induced adhesion; the guides of the corresponding genes targeted by the inhibitors of the top plots are highlighted.
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Sci Transl Med
PP2A inhibition is a druggable MEK inhibitor resistance mechanism in KRAS-mutant lung cancer cells. [Abstract]2018 Jul 18;10(450):eaaq1093. PMID: 30021885 -
Exp Hematol Oncol
Gut fungi enhances immunosuppressive function of myeloid-derived suppressor cells by activating PKM2-dependent glycolysis to promote colorectal tumorigenesis. [Abstract]2022 Nov 8;11(1):88. PMID: 36348389
R406 free base purchased from MedChemExpress. Usage Cited in: Exp Hematol Oncol. 2022 Nov 8;11(1):88. [Abstract]
R406 (1-2 μM; 18-24 h) markedly inhibited C. tropicalis-induced PKM2 Tyr105 phosphorylation and PKM2 nuclear translocation in MDSCs by suppressing Syk.
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Theranostics
Adjuvant-free peptide vaccine targeting Clec9a on dendritic cells can induce robust antitumor immune response through Syk/IL-21 axis. [Abstract]2021 May 24;11(15):7308-7321. PMID: 34158852
R406 free base purchased from MedChemExpress. Usage Cited in: Theranostics. 2021 May 24;11(15):7308-7321. [Abstract]
The induction of IL-21 secretion by CBP-12-OVA was inhibited by R406, an inhibitor of Syk phosphorylation. FL-DCs were incubated with 2.5 µM R406 for 1 h, and then cultured with 100 µg/mL of the indicated peptides for 6 h at 37 °C. IL-21 positive frequency was determined by ICS assay.
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J Adv Res
METTL3 promotes neutrophil extracellular trap formation via SYK/ERK/MEK signaling during acute lung injury. [Abstract]2026 Jan 22:S2090-1232(26)00069-X. PMID: 41579954 -
Redox Biol
HDAC11 negatively regulates antifungal immunity by inhibiting Nos2 expression via binding with transcriptional repressor STAT3. [Abstract]2022 Oct:56:102461. PMID: 36087429 -
Arthritis Rheumatol
Translational Biomarkers and Ex Vivo Models of Joint Tissues as a Tool for Drug Development in Rheumatoid Arthritis. [Abstract]2018 Sep;70(9):1419-1428. PMID: 29669391 -
Cell Rep Med
MFGE8 induces anti-PD-1 therapy resistance by promoting extracellular vesicle sorting of PD-L1. [Abstract]2025 Jan 16:101922. PMID: 39842432 -
Mater Today Bio
2024 Mar 22:26:101037. PMID: 38586870 -
J Neuroinflammation
Metformin attenuates central sensitization by regulating neuroinflammation through the TREM2-SYK signaling pathway in a mouse model of chronic migraine. [Abstract]2024 Dec 3;21(1):318. PMID: 39627853 -
Cell Death Dis
Activation of AKT via a dual mechanism enhances the susceptibility of melanoma cells to glucose deprivation. [Abstract]2025 Aug 7;16(1):595. PMID: 40774947 -
Cell Commun Signal
Mitochondria-mediated ferroptosis induced by CARD9 ablation prevents MDSCs-dependent antifungal immunity. [Abstract]2024 Apr 2;22(1):210. PMID: 38566195 -
Blood Adv
Activating pyruvate kinase improves red blood cell integrity by reducing band 3 tyrosine phosphorylation. [Abstract]2024 Nov 12;8(21):5653-5662. PMID: 39265169 -
Cell Rep
Pharmacological boosting of cGAS activation sensitizes chemotherapy by enhancing antitumor immunity. [Abstract]2023 Mar 20;42(3):112275. PMID: 36943864 -
Atherosclerosis
Inhibition of vascular neointima hyperplasia by FGF21 associated with FGFR1/Syk/NLRP3 inflammasome pathway in diabetic mice. [Abstract]2019 Oct;289:132-142. PMID: 31513948 -
Front Pharmacol
Inhibition of Spleen Tyrosine Kinase Restores Glucocorticoid Sensitivity to Improve Steroid-Resistant Asthma. [Abstract]2022 May 5;13:885053. PMID: 35600871 -
iScience
Decoding sunitinib resistance in ccRCC: Metabolic-reprogramming-induced ABAT and GABAergic system shifts. [Abstract]2024 Jun 28;27(7):110415. PMID: 39100925 -
iScience
SWI/SNF complex-mediated chromatin remodeling in Candida glabrata promotes immune evasion. [Abstract]2024 Mar 27;27(4):109607. PMID: 38632999 -
iScience
Heat-killed Mycobacterium tuberculosis induces trained immunity in vitro and in vivo administered systemically or intranasally. [Abstract]2024 Jan 11;27(2):108869. PMID: 38318361 -
J Biol Chem
Aspartyl proteases in Candida glabrata are required for suppression of the host innate immune response. [Abstract]2018 Apr 27;293(17):6410-6433. PMID: 29491142 -
ACS Infect Dis
Coordinated Regulation of TLR2 Signaling by Neu1 Sialidase and the Siglec-5/Siglec-14 Receptor Pair During Mycoplasma pneumoniae Infection. [Abstract]2026 Jun 25. PMID: 42350323 -
ACS Infect Dis
Sialylated Lipooligosaccharide Contributes to Glaesserella parasuis Penetration of Porcine Respiratory Epithelial Barrier. [Abstract]2021 Mar 12;7(3):661-671. PMID: 33645216 -
Life Metab
Intermittent fasting inhibits platelet activation and thrombosis through the intestinal metabolite indole-3-propionate. [Abstract]2025 Jan 29;4(2):loaf002. PMID: 40078933 -
Mol Immunol
Tanshinone I limits inflammasome activation of macrophage via docking into Syk to alleviate DSS-induced colitis in mice. [Abstract]2024 Jul 31:173:88-98. PMID: 39088935 -
J Pharmacol Sci
Effects of a spleen tyrosine kinase inhibitor on progression of the lupus nephritis in mice. [Abstract]2017 May;134(1):29-36. PMID: 28479222
R406 free base purchased from MedChemExpress. Usage Cited in: J Pharmacol Sci. 2017 May;134(1):29-36. [Abstract]
The effects of R406 treatment on the phosphorylation of 3BP2 and p38MAPK in white blood cells from the spleens of NZB/W F1 mice. (A) The phosphorylation of the 3BP2 and (B) the phosphorylation of p38MAPK in the renal cortex of control and R406-treated mice.
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BMC Cardiovasc Disord
Sodium tanshinone IIA sulfonate protects vascular relaxation in ApoE-knockout mice by inhibiting the SYK-NLRP3 inflammasome-MMP2/9 pathway. [Abstract]2024 Jul 12;24(1):354. PMID: 38992615 -
Scand J Immunol
Isoliquiritigenin limits inflammasome activation of macrophage via docking into Syk to alleviate murine non-alcoholic fatty liver disease. [Abstract]2024 Apr 26:e13371. PMID: 38671579 -
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Ann Transl Med
Upregulated miR-155 inhibits inflammatory response induced by C. albicans in human monocytes derived dendritic cells via targeting p65 and BCL-10. [Abstract]2019 Dec;7(23):758. PMID: 32042774 -
Solvent & Solubility
DMSO : 25 mg/mL (53.14 mM; ultrasonic and warming and heat to 60°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: 2.5 mg/mL (5.31 mM); Suspended solution; Need ultrasonic
This protocol yields a suspended solution of 2.5 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Purity & Documentation
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Data Sheet (277 KB)
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SDS (393 KB)
- English - EN (393 KB)
- Français - FR (393 KB)
- Deutsch - DE (393 KB)
- Norwegian - NO (393 KB)
- Español - ES (393 KB)
- Swedish - SV (393 KB)
- Italian - IT (393 KB)
- Korean - KR (393 KB)
- Portuguese - PT (393 KB)
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Handling Instructions (2659 KB)
References
[1]. Sylvia Braselmann, et al. R406, an orally available spleen tyrosine kinase inhibitor blocks fc receptor signaling and reduces immune complex-mediated inflammation. J Pharmacol Exp Ther. 2006 Dec;319(3):998-1008. [Content Brief]
[2]. Hoon-Suk Cha , et al. A novel spleen tyrosine kinase inhibitor blocks c-Jun N-terminal kinase-mediated gene expression in synoviocytes. J Pharmacol Exp Ther. 2006 May;317(2):571-8. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.1256 mL | 10.6281 mL | 21.2562 mL | 53.1406 mL |
| 5 mM | 0.4251 mL | 2.1256 mL | 4.2512 mL | 10.6281 mL | |
| 10 mM | 0.2126 mL | 1.0628 mL | 2.1256 mL | 5.3141 mL | |
| 15 mM | 0.1417 mL | 0.7085 mL | 1.4171 mL | 3.5427 mL | |
| 20 mM | 0.1063 mL | 0.5314 mL | 1.0628 mL | 2.6570 mL | |
| 25 mM | 0.0850 mL | 0.4251 mL | 0.8502 mL | 2.1256 mL | |
| 30 mM | 0.0709 mL | 0.3543 mL | 0.7085 mL | 1.7714 mL | |
| 40 mM | 0.0531 mL | 0.2657 mL | 0.5314 mL | 1.3285 mL | |
| 50 mM | 0.0425 mL | 0.2126 mL | 0.4251 mL | 1.0628 mL |