[CAS NO. 1229208-44-9] Entospletinib
PRODUCTS SPECIFICATIONS [1229208-44-9]
DESCRIPTION [1229208-44-9]
Overview
| MDL | MFCD28099806 |
|---|---|
| Molecular Weight | 411.46 |
| Molecular Formula | C23H21N7O |
| SMILES | C12=NC=CN1C=C(C3=CC4=C(C=C3)C=NN4)N=C2NC5=CC=C(N6CCOCC6)C=C5 |
4 Publications Citing Use of MCE
Summary
Entospletinib (GS-9973) is an orally bioavailable, selective Syk inhibitor with an IC 50 of 7.7 nM.
IC50 & Target
IC50: 7.7 nM (Syk)
In Vitro
Entospletinib (GS-9973) shows good bidirectional permeability across Caco-2 cell monolayers in vitro. In cells, Entospletinib (GS-9973) also shows excellent selectivity for Syk, and potently inhibits BCR-mediated activation and proliferation of B-cells as well as immune-complex-stimulated cytokine production in monocytes [1] . The combination of idelalisib and Entospletinib (GS-9973) synergistically inhibits CLL cell viability and further disrupts chemokine signaling [2] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
Entospletinib (GS-9973) (1 mg/kg, p.o.) shows moderate to high bioavailability in rat and dog. In a rat collagen-induced arthritis model, Entospletinib (GS-9973) (1-10 mg/kg, p.o.) significantly inhibits ankle inflammation. Moreover, Entospletinib (GS-9973) also shows disease-modifying activity in multiple histological measurements, including inhibition of pannus formation, cartilage damage, bone resorption, and peritosteal bone formation with ED 50 ranging from 1.2 to 3.9 mg/kg [1] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date | Phase |
|---|---|---|---|---|
| NCT01799889 | Gilead Sciences |
Chronic Lymphocytic Leukemia|Mantle Cell Lymphoma|Diffuse Large B-cell Lymphoma|Non-FL Indolent Non-Hodgkin´s Lymphoma|Follicular Lymphoma
|
March 14, 2013 | Phase 2 |
| NCT02457598 | Gilead Sciences |
B-cell Malignancies
|
June 16, 2015 | Phase 1 |
| NCT03010358 | Alexey Danilov, MD|Gilead Sciences|Oregon Health and Science University|OHSU Knight Cancer Institute |
Anemia|B-Cell Prolymphocytic Leukemia|Grade 1 Follicular Lymphoma|Grade 2 Follicular Lymphoma|Grade 3a Follicular Lymphoma|Hairy Cell Leukemia|Lymphoplasmacytic Lymphoma|Mantle Cell Lymphoma|Marginal Zone Lymphoma|Recurrent Chronic Lymphocytic Leukemia|Recurrent Small Lymphocytic Lymphoma|Refractory Chronic Lymphocytic Leukemia|Refractory Small Lymphocytic Lymphoma|Richter Syndrome
|
July 17, 2017 | Phase 1|Phase 2 |
| NCT02568683 | Gilead Sciences |
Non-Hodgkin Lymphoma
|
February 11, 2016 | Phase 1|Phase 2 |
| NCT03013998 | Beat AML, LLC |
Previously Untreated Acute Myeloid Leukemia
|
November 2016 | Phase 1|Phase 2 |
| NCT02343939 | Gilead Sciences |
Acute Myeloid Leukemia
|
July 1, 2015 | Phase 1|Phase 2 |
| NCT02521376 | Gilead Sciences |
Oncology
|
November 16, 2015 | Phase 1 |
| NCT03135028 | Gilead Sciences |
Hematologic Malignancy|Acute Myeloid Leukemia
|
May 19, 2017 | Phase 1 |
| NCT02404220 | Gilead Sciences |
Acute Lymphoblastic Leukemia
|
May 6, 2015 | Phase 1|Phase 2 |
| NCT05020665 | Kronos Bio |
Nucleophosmin 1-mutated Acute Myeloid Leukemia
|
November 30, 2021 | Phase 3 |
| NCT01796470 | Gilead Sciences |
Chronic Lymphocytic Leukemia|Mantle Cell Lymphoma|Diffuse Large B-cell Lymphoma|Indolent Non-Hodgkin´s Lymphoma
|
June 20, 2013 | Phase 2 |
| NCT03225924 | The Lymphoma Academic Research Organisation |
DLBCL
|
July 26, 2017 | Phase 1|Phase 2 |
| NCT02983617 | Gilead Sciences|German CLL Study Group |
Chronic Lymphocytic Leukemia
|
April 6, 2017 | Phase 2 |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : ≥ 43 mg/mL ( 104.51 mM )
* "≥" means soluble, but saturation unknown.
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 2.4304 mL | 12.1518 mL | 24.3037 mL |
| 5 mM | 0.4861 mL | 2.4304 mL | 4.8607 mL |
| 10 mM | 0.2430 mL | 1.2152 mL | 2.4304 mL |
-
1.
Add each solvent one by one: 10% DMSO >> 90% corn oil
Solubility: ≥ 2.5 mg/mL (6.08 mM); Clear solution
References
- [1] Currie KS, et al. Discovery of GS-9973, a Selective and Orally Efficacious Inhibitor of Spleen Tyrosine Kinase. J Med Chem. 2014 May 8;57(9):3856-73.
- [2] Burke RT, et al. A potential therapeutic strategy for chronic lymphocytic leukemia by combining Idelalisib and GS-9973, a novel spleen tyrosine kinase (Syk) inhibitor. Oncotarget. 2014 Feb 28;5(4):908-15.
Synonyms