Synonym
AS604850; AS 604850; AS-604850.
IUPAC/Chemical Name
(Z)-5-((2,2-difluorobenzo[d][1,3]dioxol-5-yl)methylene)thiazolidine-2,4-dione
InChi Key
SRLVNYDXMUGOFI-YWEYNIOJSA-N
InChi Code
InChI=1S/C11H5F2NO4S/c12-11(13)17-6-2-1-5(3-7(6)18-11)4-8-9(15)14-10(16)19-8/h1-4H,(H,14,15,16)/b8-4-
SMILES Code
O=C(NC/1=O)SC1=C/C2=CC=C(OC(F)(F)O3)C3=C2
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
Biological target:
AS-604850 is a potent, selective and ATP-competitive PI3Kγ inhibitor with an IC50 value of 0.25 μM and a Ki value of 0.18 μM.
In vitro activity:
Preincubation with AS604850 caused a concentration-dependent inhibition of both EoL-1 cell and human peripheral blood eosinophil chemotactic responses to PAF (Fig. 1, Fig. 2). In contrast, responses to eotaxin were unaffected by the inhibitor at concentrations up to 10 μM.
Reference: Int Immunopharmacol. 2010 Sep;10(9):1017-21. https://pubmed.ncbi.nlm.nih.gov/20685403/
In vivo activity:
AS-604850 treatment attenuated leukocyte infiltration and clinical EAE symptoms, suggesting the protective effects of PI3Kγ inhibition to CNS tissue. This study next determined whether AS-604850 treatment enhanced myelination and axon number in the spinal cord around 24 days after EAE onset by immunostaining MBP and neurofilament or by detecting myelin sheath with LFB staining. Compared to normal control mice, vehicle-treated EAE mice exhibited remarkably reduced myelin and axonal structures in the spinal cord, especially at the lumbar level (Fig. 3A and 4). Consistently, numerous groups reported obvious myelin and axonal loss along the white matter tracts in EAE mice. Nevertheless, EAE mice treated with AS-604850 displayed significantly increased MBP, LFB and NF-staining signals at different white matter areas of the spinal cord (Fig. 3A–C and 4). Therefore, systemic treatment with PI3Kγ inhibitor reduced demyelination and axonal loss in EAE mice.
Reference: Neuroscience. 2013 Dec 3;253:89-99. https://pubmed.ncbi.nlm.nih.gov/24012746/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
112.3 |
393.84 |
| DMSO:PBS (pH 7.2) (1:3) |
0.5 |
1.75 |
| DMF |
20.0 |
70.12 |
| Ethanol |
5.0 |
17.53 |
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
285.22
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:
1. Hasan AM, Mourtada-Maarabouni M, Hameed MS, Williams GT, Dent G. Phosphoinositide 3-kinase gamma mediates chemotactic responses of human eosinophils to platelet-activating factor. Int Immunopharmacol. 2010 Sep;10(9):1017-21. doi: 10.1016/j.intimp.2010.05.014. Epub 2010 Jun 4. PMID: 20685403.
2. Li H, Park D, Abdul-Muneer PM, Xu B, Wang H, Xing B, Wu D, Li S. PI3Kγ inhibition alleviates symptoms and increases axon number in experimental autoimmune encephalomyelitis mice. Neuroscience. 2013 Dec 3;253:89-99. doi: 10.1016/j.neuroscience.2013.08.051. Epub 2013 Sep 3. PMID: 24012746.
In vitro protocol:
1. Hasan AM, Mourtada-Maarabouni M, Hameed MS, Williams GT, Dent G. Phosphoinositide 3-kinase gamma mediates chemotactic responses of human eosinophils to platelet-activating factor. Int Immunopharmacol. 2010 Sep;10(9):1017-21. doi: 10.1016/j.intimp.2010.05.014. Epub 2010 Jun 4. PMID: 20685403.
In vivo protocol:
1. Li H, Park D, Abdul-Muneer PM, Xu B, Wang H, Xing B, Wu D, Li S. PI3Kγ inhibition alleviates symptoms and increases axon number in experimental autoimmune encephalomyelitis mice. Neuroscience. 2013 Dec 3;253:89-99. doi: 10.1016/j.neuroscience.2013.08.051. Epub 2013 Sep 3. PMID: 24012746.
1: Li H, Park D, Abdul-Muneer PM, Xu B, Wang H, Xing B, Wu D, Li S. PI3Kγ inhibition alleviates symptoms and increases axon number in experimental autoimmune encephalomyelitis mice. Neuroscience. 2013 Dec 3;253:89-99. doi: 10.1016/j.neuroscience.2013.08.051. Epub 2013 Sep 3. PubMed PMID: 24012746.
2: Cain RJ, Vanhaesebroeck B, Ridley AJ. Different PI 3-kinase inhibitors have distinct effects on endothelial permeability and leukocyte transmigration. Int J Biochem Cell Biol. 2012 Nov;44(11):1929-36. doi: 10.1016/j.biocel.2012.07.009. Epub 2012 Jul 17. PubMed PMID: 22814170.
3: Sun M, Hillmann P, Hofmann BT, Hart JR, Vogt PK. Cancer-derived mutations in the regulatory subunit p85alpha of phosphoinositide 3-kinase function through the catalytic subunit p110alpha. Proc Natl Acad Sci U S A. 2010 Aug 31;107(35):15547-52. doi: 10.1073/pnas.1009652107. Epub 2010 Aug 16. PubMed PMID: 20713702; PubMed Central PMCID: PMC2932613.
4: Hasan AM, Mourtada-Maarabouni M, Hameed MS, Williams GT, Dent G. Phosphoinositide 3-kinase gamma mediates chemotactic responses of human eosinophils to platelet-activating factor. Int Immunopharmacol. 2010 Sep;10(9):1017-21. doi: 10.1016/j.intimp.2010.05.014. Epub 2010 Jun 4. PubMed PMID: 20685403.
5: Hohenester S, Gates A, Wimmer R, Beuers U, Anwer MS, Rust C, Webster CR. Phosphatidylinositol-3-kinase p110γ contributes to bile salt-induced apoptosis in primary rat hepatocytes and human hepatoma cells. J Hepatol. 2010 Nov;53(5):918-26. doi: 10.1016/j.jhep.2010.05.015. Epub 2010 Jul 17. PubMed PMID: 20675006; PubMed Central PMCID: PMC2949543.
6: Camps M, Rückle T, Ji H, Ardissone V, Rintelen F, Shaw J, Ferrandi C, Chabert C, Gillieron C, Françon B, Martin T, Gretener D, Perrin D, Leroy D, Vitte PA, Hirsch E, Wymann MP, Cirillo R, Schwarz MK, Rommel C. Blockade of PI3Kgamma suppresses joint inflammation and damage in mouse models of rheumatoid arthritis. Nat Med. 2005 Sep;11(9):936-43. Epub 2005 Aug 28. PubMed PMID: 16127437.
