Size | Price | |
---|---|---|
5mg | ||
10mg | ||
25mg | ||
50mg |
Nemiralisib HCl (GSK-2269557; GSK2269557) is a novel and potent PI3Kδ inhibitor currently in clinical trials for the treatment of respiratory diseases such as asthma and COPD. GSK-2269557 is highly selective for PI3Kδ over the closely related isoforms. PI3Kδ is overactive in leukocytes, making it an attractive target for the treatment of inflammatory conditions, such as asthma,6 chronic obstructive pulmonary disease (COPD), and autoimmune diseases.
ln Vitro |
The highly selective nature of nemiralisib hydrochloride for PI3Kδ is about 1000 times greater than that of the closely related isomers PI3Kα (pIC50=5.3), PI3Kβ (pIC50=5.8), and PI3Kγ (pIC50=5.2). Peripheral blood mononuclear (PBMC) assays demonstrate a pIC50 of 9.7 for Nemiralisib hydrochloride-induced inhibition of IFNγ [1].
|
---|---|
ln Vivo |
In order to assess the suitability of this product series for inhalation administration clearance in rat microsomes, Sprague Dawley male rats were used to collect in vivo pharmacokinetic data. Nemiralisib hydrochloride, for example, was given to rats either intravenously or orally at doses of 3 mg/kg and 1 mg/kg, respectively (n = 2 rats/route). In the disease-associated brown Norway rat acute OVA model of type 2 helper T cell (Th2)-driven lung inflammation, nemalisib hydrochloride is effective [1].
|
References |
[1]. Down K et al. Optimization of Novel Indazoles as Highly Potent and Selective Inhibitors of Phosphoinositide 3-Kinase δ for the Treatment of Respiratory Disease
|
Molecular Formula |
C26H29CLN6O
|
---|---|
Molecular Weight |
477.01
|
Exact Mass |
476.20914
|
CAS # |
1254036-77-5
|
Related CAS # |
Nemiralisib;1254036-71-9
|
Appearance |
Typically exists as solids (or liquids in special cases) at room temperature
|
SMILES |
CC(C)N(CC1)CCN1CC2=CN=C(C3=CC(C4=CC=CC5=C4C=CN5)=CC6=C3C=NN6)O2.[H]Cl
|
InChi Key |
GECUEJGEJLAXQA-UHFFFAOYSA-N
|
InChi Code |
InChI=1S/C26H28N6O.ClH/c1-17(2)32-10-8-31(9-11-32)16-19-14-28-26(33-19)22-12-18(13-25-23(22)15-29-30-25)20-4-3-5-24-21(20)6-7-27-24/h3-7,12-15,17,27H,8-11,16H2,1-2H3,(H,29,30)1H
|
Chemical Name |
2-(6-(1H-indol-4-yl)-1H-indazol-4-yl)-5-((4-isopropylpiperazin-1-yl)methyl)oxazole hydrochloride
|
Synonyms |
Nemiralisib HClGSK2269557 GSK 2269557 GSK-2269557 Nemiralisib hydrochloride.
|
HS Tariff Code |
2934.99.9001
|
Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
---|---|
Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80: Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 :Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400  (Please use freshly prepared in vivo formulations for optimal results.) |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 2.0964 mL | 10.4820 mL | 20.9639 mL | |
5 mM | 0.4193 mL | 2.0964 mL | 4.1928 mL | |
10 mM | 0.2096 mL | 1.0482 mL | 2.0964 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.