AS-604850
featured

    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 406318

CAS#: 648449-76-7

Description: AS-604850 is a selective PI3Kγ inhibitor, which significantly reduced the number of infiltrated leukocytes in the CNS and ameliorated the clinical symptoms of EAE mice. Treatment with this PI3Kγ inhibitor enhanced myelination and axon number in the spinal cord of EAE mice. PI3Kγ contributes to development of autoimmune CNS inflammation and that PI3Kγ blockade may provide a great potential for treating patients with MS.

Chemical Structure

img
AS-604850
CAS# 648449-76-7
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 406318
Name: AS-604850
CAS#: 648449-76-7
Chemical Formula: C11H5F2NO4S
Exact Mass: 284.99
Molecular Weight: 285.220
Elemental Analysis: C, 46.32; H, 1.77; F, 13.32; N, 4.91; O, 22.44; S, 11.24

Price and Availability

Size Price Availability Quantity
10mg USD 90
25mg USD 150
50mg USD 250
100mg USD 450
200mg USD 750
500mg USD 1250
1g USD 2150
2g USD 3750
5g USD 4950
Bulk inquiry

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

Appearance: Solid powder

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:         

Product Data:
Product Data
Instruction:
View handling instruction
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/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. 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

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.

Recalculate based on batch purity %
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.

Molarity Calculator

Calculate the mass, volume, or concentration required for a solution.
=
x
x
g/mol

*When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and SDS / CoA (available online).

Reconstitution Calculator

The reconstitution calculator allows you to quickly calculate the volume of a reagent to reconstitute your vial. Simply enter the mass of reagent and the target concentration and the calculator will determine the rest.

=
÷

Dilution Calculator

Calculate the dilution required to prepare a stock solution.
x
=
x

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.