Structure of Entospletinib
CAS No.: 1229208-44-9
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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.
GS-9973 is a Syk inhibitor with IC50 value of 7.7 nM which is used for the treatment of autoimmune and oncology indications.
Synonyms: GS-9973
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Batch number can be found on the product's label following the word 'Batch'.
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Nanae Asakawa ; Toshiaki Oharaseki ; Yuki Yokouchi ; Noriko Miura ; Naohito Ohno ; Kei Takahashi
Abstract: Background: The activation of innate immunity may be involved in the development of Candida albicans-induced murine vasculitis, which resembles Kawasaki disease (KD)vasculitis. This study aimed to histologically clarify the time course of the development of vasculitis in this model in detail and to estimate the potential role of spleen tyrosine kinase (Syk) inhibitors in KD vasculitis. Methods and Results: DBA/2 male mice were intraperitoneally injected with a vasculitis_x005f_x0002_inducing substance and treated with a Syk inhibitor (R788 or GS-9973). Systemic vasculitis, especially in the aortic annulus area, was histologically evaluated. Regarding lesions in the aortic annulus area, some mice in the untreated control group already showed initiation of vasculitis 1 day after the final injection of a vasculitis-inducing substance. The vasculitis expanded over time. Inflammation occurred more frequently at the aortic root than at the coronary artery. The distribution of inflammatory cells was limited to the intima, intima plus adventitia, or all layers. In the Syk inhibitor-treated groups, only one mouse had vasculitis at all observation periods. The severity and area of the vasculitis were reduced by both Syk inhibitors. Conclusion: Candida albicans-induced murine vasculitis may occur within 1 day after the injection of a vasculitis-inducing substance. Additionally, Syk inhibitors suppress murine vasculitis.
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Keywords: Kawasaki disease ; vasculitis ; Candida albicans ; murine model ; Syk
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CAS No. : | 1229208-44-9 |
Formula : | C23H21N7O |
M.W : | 411.46 |
SMILES Code : | C12=NC=CN1C=C(C3=CC4=C(C=C3)C=NN4)N=C2NC5=CC=C(N6CCOCC6)C=C5 |
Synonyms : |
GS-9973
|
MDL No. : | MFCD28099806 |
InChI Key : | XSMSNFMDVXXHGJ-UHFFFAOYSA-N |
Pubchem ID : | 59473233 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Target |
|
In Vitro:
Cell Line
|
Concentration | Treated Time | Description | References |
MEC-1 cells | 100 nM | 96 hours | GS-5829 significantly inhibits the proliferation of MEC-1 cells, but does not affect cell viability. | PMC7272263 |
CLL cells | 400 nM | 120 hours | GS-5829 significantly induced apoptosis in CLL cells, reducing the percentage of viable cells from 94.8% to 64.4% | PMC7272263 |
NCI-H460/MX20 | 3 μM | 72 hours | GS-9973 reversed the drug resistance of NCI-H460/MX20 cells to mitoxantrone or doxorubicin by blocking ABCG2 efflux activity and downregulating ABCG2 expression at the protein level but did not alter the ABCG2 mRNA expression and subcellular localization of the ABCG2 protein. | PMC8315011 |
HEK293/ABCG2 | 3 μM | 72 hours | GS-9973 significantly increased the cytotoxicity of mitoxantrone and doxorubicin in HEK293/ABCG2 cells, reversing ABCG2-mediated multidrug resistance. | PMC8315011 |
Mouse neutrophils | 0.1 µM, 1 µM, 10 µM | 10 minutes | Entospletinib dose-dependently reduced the cell responses of iμMune complex- or integrin ligand-activated neutrophils, including superoxide release, cell spreading, and cytokine release. | PMC10725968 |
In Vivo:
Species
|
Animal Model
|
Administration | Dosage | Frequency | Description | References |
Mice | GVHD model | Oral | 1 mM | single injection | Entospletinib significantly improved clinical eye scores, alopecia scores, and skin scores in GVHD mice and prolonged survival. 60% of ENTO-treated mice survived to day +120 compared with 10% of placebo-treated mice. | PMC6237454 |
Mice | K/BxN serum transfer arthritis model | Oral | 0.06% or 0.02% | Starting from day +12 after HCT until the end of the experiment | Entospletinib dose-dependently reduced the macroscopic signs of joint inflammation, while it did not affect the health status of the animals. Local neutrophil accumulation and cytokine levels were reduced, while macrophage accumulation and synovial fibroblast numbers were not significantly altered. | PMC10725968 |
Clinical Trial:
NCT Number | Conditions | Phases | Recruitment | Completion Date | Locations |
NCT02521376 | Oncology | PHASE1 | COMPLETED | 2017-10-25 | Clinical Pharmacology of Miami... More >>, Inc. (CPMI), Miami, Florida, United States|Orlando Clinical Research Center, Orlando, Florida, United States|DaVita Clinical Research, Minneapolis, Minnesota, United States|The Texas Liver Institute, San Antonio, Texas, United States|APEX GmBH, Munich, Germany|Auckland Clinical Studies, Auckland, New Zealand Less << |
Bio Calculators | ||||
Preparing Stock Solutions | ![]() |
1mg | 5mg | 10mg |
1 mM 5 mM 10 mM |
2.43mL 0.49mL 0.24mL |
12.15mL 2.43mL 1.22mL |
24.30mL 4.86mL 2.43mL |
Tags: Entospletinib | GS-9973 | GS9973 | GS 9973 | Syk inhibitor | Spleen tyrosine kinase | 1229208-44-9
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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. |
P370 + P376 | In case of fire: Stop leak if safe to Do so. |
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Storage | |
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P401 | |
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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 |
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H311 | Toxic in contact with skin |
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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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