Synonym
AS 605240; AS605240; AS-605240.
IUPAC/Chemical Name
(E)-5-(quinoxalin-6-ylmethylene)thiazolidine-2,4-dione
InChi Key
SQWZFLMPDUSYGV-UXBLZVDNSA-N
InChi Code
InChI=1S/C12H7N3O2S/c16-11-10(18-12(17)15-11)6-7-1-2-8-9(5-7)14-4-3-13-8/h1-6H,(H,15,16,17)/b10-6+
SMILES Code
O=C(NC/1=O)SC1=C\C2=CC=C3N=CC=NC3=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-605240 is a specific and orally active inhibitor of the PI3Kγ, with an IC50 of 8 nM, and a Ki of 7.8 nM.
In vitro activity:
T-cells were stimulated in the presence of HLA-matched (DR401+) antigen-presenting-cells and a specific GAD65-peptide at different concentrations of the PI3Kγ-inhibitor, AS605240. As shown in Fig 4 proliferation of the T-cell-clone was significantly reduced when cultured in the presence of AS605240, even at low concentrations of the drug suggesting relevance of this pathway in T-cell activation and proliferation in human autoreactive-T-cells.
Reference: PLoS One. 2017; 12(1): e0169695. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5231340/
In vivo activity:
Treatment with AS605240 at indicated doses (5, 15 and 25 mg/kg) significantly (p < 0.01 and p < 0.001) decreased escape latency compared with the STZ group. The standard donepezil treated group showed similar effects as compared with 25 mg/kg of AS605240 treated group (p < 0.001). Similar effects were observed in the spatial probe test with the platform removed. STZ treated rats had a significantly (p < 0.001) decreased amount of time spent in the target quadrant than the control group rats. However, the amount of time spent in the target quadrant by the rats in the AS605240 treated groups was much longer than that in the STZ group (Figure 3B(Fig. 3), p < 0.01 and p < 0.001), supporting a protective effect on learning and memory.
Reference: EXCLI J. 2020; 19: 71–85. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7003642/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
1.7 |
6.76 |
| DMF |
0.2 |
0.78 |
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
257.27
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. Azzi J, Thueson L, Moore R, Abdoli R, Reijonen H, Abdi R. PI3Kγ Deficient NOD-Mice Are Protected from Diabetes by Restoring the Balance of Regulatory to Effector-T-Cells. PLoS One. 2017 Jan 12;12(1):e0169695. doi: 10.1371/journal.pone.0169695. PMID: 28081180; PMCID: PMC5231340.
2. Silveira AB, Laranjeira AB, Rodrigues GO, Leal PC, Cardoso BA, Barata JT, Yunes RA, Zanchin NI, Brandalise SR, Yunes JA. PI3K inhibition synergizes with glucocorticoids but antagonizes with methotrexate in T-cell acute lymphoblastic leukemia. Oncotarget. 2015 May 30;6(15):13105-18. doi: 10.18632/oncotarget.3524. PMID: 25869207; PMCID: PMC4537002.
3. Alluri R, Ambati SR, Routhu K, Kopalli SR, Koppula S. Phosphoinositide 3-kinase inhibitor AS605240 ameliorates streptozotocin-induced Alzheimer's disease like sporadic dementia in experimental rats. EXCLI J. 2020 Jan 6;19:71-85. doi: 10.17179/excli2019-1997. PMID: 32038117; PMCID: PMC7003642.
4. Shang S, Liu L, Wu X, Fan F, Hu E, Wang L, Ding Y, Zhang Y, Lu X. Inhibition of PI3Kγ by AS605240 Protects tMCAO Mice by Attenuating Pro-Inflammatory Signaling and Cytokine Release in Reactive Astrocytes. Neuroscience. 2019 Sep 1;415:107-120. doi: 10.1016/j.neuroscience.2019.06.001. Epub 2019 Jun 11. PMID: 31195053.
In vitro protocol:
1. Azzi J, Thueson L, Moore R, Abdoli R, Reijonen H, Abdi R. PI3Kγ Deficient NOD-Mice Are Protected from Diabetes by Restoring the Balance of Regulatory to Effector-T-Cells. PLoS One. 2017 Jan 12;12(1):e0169695. doi: 10.1371/journal.pone.0169695. PMID: 28081180; PMCID: PMC5231340.
2. Silveira AB, Laranjeira AB, Rodrigues GO, Leal PC, Cardoso BA, Barata JT, Yunes RA, Zanchin NI, Brandalise SR, Yunes JA. PI3K inhibition synergizes with glucocorticoids but antagonizes with methotrexate in T-cell acute lymphoblastic leukemia. Oncotarget. 2015 May 30;6(15):13105-18. doi: 10.18632/oncotarget.3524. PMID: 25869207; PMCID: PMC4537002.
In vivo protocol:
1. Alluri R, Ambati SR, Routhu K, Kopalli SR, Koppula S. Phosphoinositide 3-kinase inhibitor AS605240 ameliorates streptozotocin-induced Alzheimer's disease like sporadic dementia in experimental rats. EXCLI J. 2020 Jan 6;19:71-85. doi: 10.17179/excli2019-1997. PMID: 32038117; PMCID: PMC7003642.
2. Shang S, Liu L, Wu X, Fan F, Hu E, Wang L, Ding Y, Zhang Y, Lu X. Inhibition of PI3Kγ by AS605240 Protects tMCAO Mice by Attenuating Pro-Inflammatory Signaling and Cytokine Release in Reactive Astrocytes. Neuroscience. 2019 Sep 1;415:107-120. doi: 10.1016/j.neuroscience.2019.06.001. Epub 2019 Jun 11. PMID: 31195053.
1: Azzi J, Moore RF, Elyaman W, Mounayar M, El Haddad N, Yang S, Jurewicz M, Takakura A, Petrelli A, Fiorina P, Ruckle T, Abdi R. The novel therapeutic effect of phosphoinositide 3-kinase-γ inhibitor AS605240 in autoimmune diabetes. Diabetes. 2012 Jun;61(6):1509-18. doi: 10.2337/db11-0134. Epub 2012 Mar 8. PubMed PMID: 22403300; PubMed Central PMCID: PMC3357271.
2: Song LF, Jiang W, Qing Y, Hu XH, Li Y, Tong QY, Wu XH. [The antagonistic effect of PI3K-gamma inhibitor AS605240 on cardiac hypertrophy and cardiac fibrosis induced by isoproterenol in rats]. Sichuan Da Xue Xue Bao Yi Xue Ban. 2011 Jul;42(4):471-4. Chinese. PubMed PMID: 21866628.
3: Wei X, Han J, Chen ZZ, Qi BW, Wang GC, Ma YH, Zheng H, Luo YF, Wei YQ, Chen LJ. A phosphoinositide 3-kinase-gamma inhibitor, AS605240 prevents bleomycin-induced pulmonary fibrosis in rats. Biochem Biophys Res Commun. 2010 Jun 25;397(2):311-7. doi: 10.1016/j.bbrc.2010.05.109. Epub 2010 May 26. PubMed PMID: 20510675.
4: Jin K, Song LF, He CM, Wang ZL, Hu XH, Wu XH. [Intervention effect of PI3Kgamma inhibitor AS605240 on autoimmune myocarditis in mice]. Sichuan Da Xue Xue Bao Yi Xue Ban. 2009 Sep;40(5):817-20, 825. Chinese. PubMed PMID: 19950590.
