Synonym
GSK-2269557; GSK 2269557; GSK2269557; Nemiralisib HCl; Nemiralisib hydrochloride.
IUPAC/Chemical Name
2-(6-(1H-indol-4-yl)-1H-indazol-4-yl)-5-((4-isopropylpiperazin-1-yl)methyl)oxazole hydrochloride
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
SMILES Code
CC(C)N(CC1)CCN1CC2=CN=C(C3=CC(C4=CC=CC5=C4C=CN5)=CC6=C3C=NN6)O2.[H]Cl
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
Related CAS#
1254036-77-5 (GSK-2269557 HCl salt);
1254036-71-9 (GSK-2269557 free base)
Biological target:
Nemiralisib (GSK2269557 free base) is a potent and highly selective PI3Kδ inhibitor with a pKi of 9.9.
In vitro activity:
Optimization of lead compound 1, through extensive use of structure-based design and a focus on PI3Kδ potency, isoform selectivity, and inhaled PK properties, led to the discovery of clinical candidates 2 (GSK2269557) and 3 (GSK2292767) for the treatment of respiratory indications via inhalation. Compounds 2 and 3 are both highly selective for PI3Kδ over the closely related isoforms and are active in a disease relevant brown Norway rat acute OVA model of Th2-driven lung inflammation.
Reference: J Med Chem. 2015 Sep 24;58(18):7381-99. https://pubmed.ncbi.nlm.nih.gov/26301626/
In vivo activity:
Optimization of lead compound 1, through extensive use of structure-based design and a focus on PI3Kδ potency, isoform selectivity, and inhaled PK properties, led to the discovery of clinical candidates 2 (GSK2269557) and 3 (GSK2292767) for the treatment of respiratory indications via inhalation. Compounds 2 and 3 are both highly selective for PI3Kδ over the closely related isoforms and are active in a disease relevant brown Norway rat acute OVA model of Th2-driven lung inflammation.
Reference: J Med Chem. 2015 Sep 24;58(18):7381-99. https://pubmed.ncbi.nlm.nih.gov/26301626/
|
Solvent |
mg/mL |
mM |
comments |
| Solubility |
| Soluble in DMSO, not in water |
0.0 |
100.00 |
|
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
477.01
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
Down K, Amour A, Baldwin IR, Cooper AW, Deakin AM, Felton LM, Guntrip SB, Hardy C, Harrison ZA, Jones KL, Jones P, Keeling SE, Le J, Livia S, Lucas F, Lunniss CJ, Parr NJ, Robinson E, Rowland P, Smith S, Thomas DA, Vitulli G, Washio Y, Hamblin JN. Optimization of Novel Indazoles as Highly Potent and Selective Inhibitors of Phosphoinositide 3-Kinase δ for the Treatment of Respiratory Disease. J Med Chem. 2015 Sep 24;58(18):7381-99. doi: 10.1021/acs.jmedchem.5b00767. Epub 2015 Sep 3. PMID: 26301626.
In vitro protocol:
Down K, Amour A, Baldwin IR, Cooper AW, Deakin AM, Felton LM, Guntrip SB, Hardy C, Harrison ZA, Jones KL, Jones P, Keeling SE, Le J, Livia S, Lucas F, Lunniss CJ, Parr NJ, Robinson E, Rowland P, Smith S, Thomas DA, Vitulli G, Washio Y, Hamblin JN. Optimization of Novel Indazoles as Highly Potent and Selective Inhibitors of Phosphoinositide 3-Kinase δ for the Treatment of Respiratory Disease. J Med Chem. 2015 Sep 24;58(18):7381-99. doi: 10.1021/acs.jmedchem.5b00767. Epub 2015 Sep 3. PMID: 26301626.
In vivo protocol:
Down K, Amour A, Baldwin IR, Cooper AW, Deakin AM, Felton LM, Guntrip SB, Hardy C, Harrison ZA, Jones KL, Jones P, Keeling SE, Le J, Livia S, Lucas F, Lunniss CJ, Parr NJ, Robinson E, Rowland P, Smith S, Thomas DA, Vitulli G, Washio Y, Hamblin JN. Optimization of Novel Indazoles as Highly Potent and Selective Inhibitors of Phosphoinositide 3-Kinase δ for the Treatment of Respiratory Disease. J Med Chem. 2015 Sep 24;58(18):7381-99. doi: 10.1021/acs.jmedchem.5b00767. Epub 2015 Sep 3. PMID: 26301626.
1: Down KD, Amour A, Baldwin IR, Cooper AW, Deakin AM, Felton LM, Guntrip SB, Hardy C, Harrison ZA, Jones KL, Jones P, Keeling SE, Le J, Livia S, Lucas F, Lunniss CJ, Parr NJ, Robinson E, Rowland P, Smith S, Thomas DA, Vitulli G, Washio Y, Hamblin N. Optimization of Novel Indazoles as Highly Potent and Selective Inhibitors of Phosphoinostide-3-Kinase Delta for the Treatment of Respiratory Disease. J Med Chem. 2015 Aug 24. [Epub ahead of print] PubMed PMID: 26301626.
