Structure of R406 free base
CAS No.: 841290-80-0
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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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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 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
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 << |
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 |
Tags: R406 | R 406 | R-406 | Syk | FLT3 | Apoptosis | Spleen tyrosine kinase | autoimmune disease | B-cell malignancies | inflammation | 841290-80-0
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Code | Phrase |
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P304 | IF INHALED: |
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P303 + P361 + P353 | IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower. |
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P304 + P340 | IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing. |
P304 + P341 | IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
P306 + P360 | IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes. |
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P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
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P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
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H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
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H203 | Explosive; fire, blast or projection hazard |
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H242 | Heating may cause a fire |
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H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
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H290 | May be corrosive to metals |
Health hazards | |
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H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
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H333 | May be harmful if inhaled |
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H335 | May cause respiratory irritation |
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H340 | May cause genetic defects |
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H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
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H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
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