1. Protein Tyrosine Kinase/RTK
  2. Syk
  3. Entospletinib

Entospletinib  (Synonyms: GS-9973)

Cat. No.: HY-15968 Purity: 99.88%
COA Handling Instructions

Entospletinib (GS-9973) is an orally bioavailable, selective Syk inhibitor with an IC50 of 7.7 nM.

For research use only. We do not sell to patients.

Entospletinib Chemical Structure

Entospletinib Chemical Structure

CAS No. : 1229208-44-9

Size Price Stock Quantity
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO
ready for reconstitution
USD 101 In-stock
Solution
10 mM * 1 mL in DMSO USD 101 In-stock
Solid
5 mg USD 92 In-stock
10 mg USD 132 In-stock
50 mg USD 330 In-stock
100 mg USD 530 In-stock
200 mg USD 850 In-stock
500 mg   Get quote  
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Customer Review

Based on 6 publication(s) in Google Scholar

Top Publications Citing Use of Products
  • Biological Activity

  • Protocol

  • Purity & Documentation

  • References

  • Customer Review

Description

Entospletinib (GS-9973) is an orally bioavailable, selective Syk inhibitor with an IC50 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].

MedChemExpress (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 ED50 ranging from 1.2 to 3.9 mg/kg[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Clinical Trial
Molecular Weight

411.46

Formula

C23H21N7O

CAS No.
Appearance

Solid

Color

White to gray

SMILES

C12=NC=CN1C=C(C3=CC4=C(C=C3)C=NN4)N=C2NC5=CC=C(N6CCOCC6)C=C5

Shipping

Room temperature in continental US; may vary elsewhere.

Storage
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 2 years
-20°C 1 year
Solvent & Solubility
In Vitro: 

DMSO : ≥ 43 mg/mL (104.51 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

*"≥" means soluble, but saturation unknown.

Preparing
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
View the 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.

  • Molarity Calculator

  • Dilution Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass
=
Concentration
×
Volume
×
Molecular Weight *

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

Concentration (start)

C1

×
Volume (start)

V1

=
Concentration (final)

C2

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Volume (final)

V2

In Vivo:

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.

  • Protocol 1

    Add each solvent one by one:  10% DMSO    90% Corn Oil

    Solubility: ≥ 2.5 mg/mL (6.08 mM); Clear solution

    This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

g

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
%
DMSO +
+
%
Tween-80 +
%
Saline
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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).
Calculation results:
Working solution concentration: mg/mL
Method for preparing stock solution: mg drug dissolved in μL  DMSO (Stock solution concentration: mg/mL).
The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
 If the continuous dosing period exceeds half a month, please choose this protocol carefully.
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

Purity: 99.88%

References
Cell Assay
[1]

Functional impact on cellular Flt3 activity is determined by measuring compound inhibition of MV-4-11 cell proliferation. A total of 104 cells are diluted in RPMI medium containing 10% FBS in 96-well flat-bottomed tissue culture plates and incubated with compound dilutions for 72 h at 37°C. Alamar blue (10%) is added to the cells, which are incubated for an additional 12-18 h at 37°C, and inhibition of the relative cell numbers is determined by spectrophotometer readings at 570/600 nm.

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[1]

Female Lewis rats (mean mass 178 g, eight per group for collagen arthritis, four per group for normal controls) are anesthetized with isoflurane and injected with 300 μL of Freund’s incomplete adjuvant containing 2 mg/mL bovine type II collagen at the base of the tail and two sites on the back on days 0 and 6. Oral dosing (bid at 12 h intervals) is performed on arthritic days 0-7 with vehicle (Cremophor/ethanol/saline), Entospletinib (GS-9973) (1, 3, or 10 mg/kg), or the reference compound dexamethasone (Dex; 0.075 mg/kg) administered daily (qd). Rats are terminated on arthritis day 16. Efficacy evaluation is based on animal body masses, daily ankle caliper measurements, ankle diameters expressed as the area under the curve (AUC), terminal hind paw masses, and histopathologic evaluation of ankles and knees. PK is measured from plasma samples taken 0, 2, 4, 8, 12, and 24 h post last dose. The paws are fixed in formalin and processed for hemotoxylin (H) and eosin (E) microscopy. H and E sections are scored for bone resorption as follows: (0) normal; (0.5) normal on low magnification but have the earliest hint of small areas of resorption in the metaphysis with no resorption in the tarsal bones; (1) (minimal) small definite areas of resorption in distal tibial trabecular or cortical bone or in the tarsal bones, not readily apparent on low magnification, rare osteoclasts; (2) (mild) more numerous areas (<25% loss of bone in growth plate area) of resorption in distal tibial trabecular or cortical bone and tarsals apparent on low magnification, osteoclasts more numerous; (3) (moderate) obvious resorption of medullary trabecular and cortical bone without full thickness defects in both distal tibial cortices, loss of some medullary trabeculae with 26-50% loss across the growth plate and cortices, some loss in tarsal bones, lesion apparent on low magnification, osteoclasts more numerous; (4) (marked) full or nearly full thickness defects in both distal tibial cortices, often with distortion of the profile of the remaining cortical surface, marked loss of medullary bone of distal tibia (50-100% loss across the growth plate area and cortices and up to 50% loss in small tarsals if minor in tibia), numerous osteoclasts, minor to mild resorption in smaller tarsal bones; (5) (severe) full thickness defects in both distal tibial cortices with >75% loss across the growth plate and both cortices and >50% loss in tarsals, often with distortion of the profile of the remaining cortical surface, marked loss of medullary bone of distal tibia, numerous osteoclasts. Osteoclast counts (5400× fields) are performed on the ankles in the areas of greatest bone resorption.

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References

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 2.4304 mL 12.1518 mL 24.3037 mL 60.7592 mL
5 mM 0.4861 mL 2.4304 mL 4.8607 mL 12.1518 mL
10 mM 0.2430 mL 1.2152 mL 2.4304 mL 6.0759 mL
15 mM 0.1620 mL 0.8101 mL 1.6202 mL 4.0506 mL
20 mM 0.1215 mL 0.6076 mL 1.2152 mL 3.0380 mL
25 mM 0.0972 mL 0.4861 mL 0.9721 mL 2.4304 mL
30 mM 0.0810 mL 0.4051 mL 0.8101 mL 2.0253 mL
40 mM 0.0608 mL 0.3038 mL 0.6076 mL 1.5190 mL
50 mM 0.0486 mL 0.2430 mL 0.4861 mL 1.2152 mL
60 mM 0.0405 mL 0.2025 mL 0.4051 mL 1.0127 mL
80 mM 0.0304 mL 0.1519 mL 0.3038 mL 0.7595 mL
100 mM 0.0243 mL 0.1215 mL 0.2430 mL 0.6076 mL
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Entospletinib Related Classifications

Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

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