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Chemical Structure| 841290-80-0 Chemical Structure| 841290-80-0

Structure of R406 free base
CAS No.: 841290-80-0

Chemical Structure| 841290-80-0

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

Synonyms: R406; free base

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Product Details of R406 free base

CAS No. :841290-80-0
Formula : C22H23FN6O5
M.W : 470.45
SMILES Code : O=C1NC2=NC(NC3=NC(NC4=CC(OC)=C(OC)C(OC)=C4)=NC=C3F)=CC=C2OC1(C)C
Synonyms :
R406; free base
MDL No. :MFCD09970820
InChI Key :NHHQJBCNYHBUSI-UHFFFAOYSA-N
Pubchem ID :11213558

Safety of R406 free base

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

Related Pathways of R406 free base

RTK

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
CD19-selected spleen lymphocytes 2.5 μM 48 h R406 inhibits the B-cell receptor signaling pathway, leading to decreased expression of Foxm1 and Ccl3, and increased expression of p53. PMC4456291
CH12 cells 1.85 μM 18 h R406 inhibits BCR signaling, reducing phosphorylated proteins including pBTK, but not affecting pSYK. PMC10591993
CH12 cells 1.85 μM 18 h R406 inhibits BCR signaling, enhancing CH12-M and CH12-A sensitivity to FasL vesicles, leading to increased cell death. PMC10591993
chronic lymphocytic leukemia cells 100 μM 1 h To investigate the effect of R406 on chronic lymphocytic leukemia cells, results showed that R406 inhibited the anti-apoptotic effect mediated by sLAG3 PMC5477606
B1-8 splenic B cells 5 μM 60 min To test the effect of Syk inhibitor R406 on B cell activation, results showed that R406 completely blocked the dissociation of BCR oligomers. PMC4067077
TKO-M cells 5 μM 60 min To test the effect of Syk inhibitor R406 on BCR oligomer dissociation, results showed that R406 increased the antigen dose required for BCR oligomer dissociation. PMC4067077
BV2 cells 1 mM 2 h To suppress SYK to mitigate neuroinflammation PMC11467918
microglia 1 mM 24 h Inhibit SYK to detect its effect on microglial inflammatory response PMC6642102
SKOV3 2.5 µM 48 h Inhibited SYK autophosphorylation, reduced cell proliferation PMC5257279
SKOV3TR 2.5 µM Enhanced paclitaxel cytotoxicity PMC5257279
MPSC1 2.5 µM Inhibited cell proliferation PMC5257279
MPSC1TR 2.5 µM Enhanced paclitaxel cytotoxicity PMC5257279
GSC-1 1 μM 48 h R406 significantly inhibited the proliferation of GSC-1 cells, with an IC50 of 0.75 μM. PMC6494878
GSC-2 1 μM 48 h R406 significantly inhibited the proliferation of GSC-2 cells, with an IC50 of 0.89 μM. PMC6494878
U87 10 μM 48 h R406 showed weak inhibitory effect on U87 cells, with an IC50 greater than 1 mM. PMC6494878
U251 10 μM 48 h R406 showed weak inhibitory effect on U251 cells, with an IC50 greater than 1 mM. PMC6494878
C17.2 10 μM 48 h R406 showed no significant toxicity to C17.2 cells. PMC6494878

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
mice K14-HPV16 transgenic mice orally 2.0 g/kg starting at 1 month of age and continuing for a total of 12 weeks R406, by inhibiting Syk kinase activity, prevented the progression from hyperplasia to dysplasia/carcinoma in situ in K14-HPV16 mice. PMC4063283
Mice MPTP-induced Parkinson's disease model Intraperitoneal injection 5 mg/kg Once daily for five consecutive days To suppress SYK to mitigate neuroinflammation PMC11467918
mice MCAO model intraperitoneal injection 5 mg/kg once daily for 3 consecutive days Inhibit SYK to detect its effect on post-ischemic inflammatory response PMC6642102
mice SKOV3c.2 subcutaneous tumor model orally 6.5 mg/kg three-days on/three-days off cycles for four cycles Combination with paclitaxel significantly reduced tumor weight PMC5257279
BALB/c-nu/nu mice Subcutaneous tumor model Intraperitoneal injection 20 mg/kg Once daily until tumor volume reached 1000 mm³ R406 significantly delayed subcutaneous tumor growth and synergized with TMZ to inhibit tumor. PMC6494878

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT01725230 Rheumatoid Arthritis Phase 1 Completed - United States, Kansas ... More >> Research Site Overland Park, Kansas, United States Less <<
NCT01208155 Bioavailability ... More >> Pharmacokinetics Less << Phase 1 Completed - United States, Kansas ... More >> Research Site Overland Park, Kansas, United States Less <<
NCT01245790 Rheumatoid Arthritis ... More >> Renal Impairment Less << Phase 1 Completed - United States, Florida ... More >> Research Site Orlando, Florida, United States Less <<
NCT01355354 Healthy Volunteers ... More >> Rheumatoid Arthritis Less << Phase 1 Completed - United Kingdom ... More >> Research Site London, United Kingdom Less <<
NCT01197781 Drug Drug Interactions ... More >> Healthy Volunteers Less << Phase 1 Completed - United States, Kansas ... More >> Recruiting Site Overland Park, Kansas, United States Less <<
NCT01387308 Healthy Phase 1 Completed - United States, Kansas ... More >> Research Site Overland Park, Kansas, United States Less <<
NCT01276262 Scientific Terminology Rheumat... More >>oid Arthritis, Healthy Female Volunteers, Pharmacokinetics, Oral Contraceptive, Drug-drug Interaction Laymen Terminology Level of Oral Contraceptive in Blood, Oral Contraceptive, Rheumatoid Arthritis, Drug -Drug Interaction Less << Phase 1 Completed - United Kingdom ... More >> Research Site London, United Kingdom Less <<
NCT01336218 Rheumatoid Arthritis ... More >> Healthy Volunteers Less << Phase 1 Completed - United States, Kansas ... More >> Research Site Overland Park, Kansas, United States Less <<
NCT01598571 Healthy Phase 1 Completed - United Kingdom ... More >> Ruddington, Nottingham, United Kingdom Less <<
NCT01311622 Rheumatoid Arthritis ... More >> Healthy Subjects Less << Phase 1 Completed - United Kingdom ... More >> Research Site London, United Kingdom Less <<
NCT01682408 Pharmacokinetics Phase 1 Completed - United States, Kansas ... More >> Overland Park, Kansas, United States Less <<
NCT01222455 Hepatic Impairment ... More >> Healthy Volunteers Pharmacokinetics Amount of R406 in Blood Less << Phase 1 Completed - United States, Florida ... More >> Research Site Orlando, Florida, United States Less <<
NCT01645085 Healthy Volunteers Phase 1 Completed - United States, Kansas ... More >> Overland Park, Kansas, United States Less <<

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.13mL

0.43mL

0.21mL

10.63mL

2.13mL

1.06mL

21.26mL

4.25mL

2.13mL

References

 

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