Synonym
AS1949490; AS-1949490; AS 1949490
IUPAC/Chemical Name
3-[(4-chlorophenyl)methoxy]-N-[(1S)-1-phenylethyl]thiophene-2-carboxamide
InChi Key
RFZPGNRLOKVZJY-AWEZNQCLSA-N
InChi Code
InChI=1S/C20H18ClNO2S/c1-14(16-5-3-2-4-6-16)22-20(23)19-18(11-12-25-19)24-13-15-7-9-17(21)10-8-15/h2-12,14H,13H2,1H3,(H,22,23)/t14-/m0/s1
SMILES Code
O=C(C1=C(OCC2=CC=C(Cl)C=C2)C=CS1)N[C@H](C3=CC=CC=C3)C
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
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:
AS1949490 is a potent and selective SHIP-2 (SH2 domain-containing inositol 5′ phosphatase 2) inhibitor, with an IC50 of 620 nM.
In vitro activity:
Cells were first treated with vehicle or SHIP2 inhibitor AS1949490 for 24 h then treated with 1 mM H2O2 for 1 h. As indicated in Fig. 1A, western blot analysis showed that SHIP2 inhibition enhances H2O2 induced AKT and ERK1/2 phosphorylation. Furthermore, higher phosphorylation of c-Jun N-terminal kinases (JNKs) also was seen in cells treated with AS1949490 (Fig. 1A). Next, this study analyzed the impact of longer H2O2 treatment on the phosphorylation levels of these proteins. Compared to control cells and similar to the observation above, 6 h H2O2 treatment led to sustained phosphorylation of AKT at Ser473 (Fig. 1B–C). To this study’s surprise, ERK1/2 phosphorylation displayed marked and sustained activation in cells treated with AS1949490 and H2O2.
Reference: Arch Biochem Biophys. 2021 Jan 15;697:108667. https://pubmed.ncbi.nlm.nih.gov/33181128/
In vivo activity:
When cultured cortical neurons were exposed to Aβ25–35 (10), survival rate was markedly reduced (Fig. 5A). Pretreatment with AS1949490 (10 μM) significantly increased cell viability in the presence of Aβ25–35, although BDNF (1 ng/ml) had no effect. The protective efficacy of AS1949490 alone was nearly identical to that of AS1949490 plus BDNF. Similarly, when cultured cortical cells (i.e., cells prepared without Ara-C) were exposed to Aβ25–35 (25 μM), marked cell death was detected (Fig. 5B). Pretreatment with 10 μM AS1949490 (Fig. 5B) and higher concentration (10 ng/ml) of BDNF (data not shown) protected the Aβ toxicity, although 1 ng/ml BDNF had no effect. The potency of the effect of AS1949490 alone was not different from that of AS1949490 plus BDNF. These results indicate that AS1949490 directly caused neuroprotection against the Aβ toxicity.
Reference: Eur J Pharmacol. 2019 May 15;851:69-79. https://pubmed.ncbi.nlm.nih.gov/30753865/
|
Solvent |
mg/mL |
mM |
comments |
| Solubility |
| DMSO |
43.6 |
117.24 |
|
| DMSO:PBS (pH 7.2) (1:2) |
0.3 |
0.81 |
|
| DMF |
30.0 |
80.67 |
|
| Ethanol |
28.6 |
76.91 |
|
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
371.88
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 A. Scaffold dependent role of the inositol 5'-phosphatase SHIP2, in regulation of oxidative stress induced apoptosis. Arch Biochem Biophys. 2021 Jan 15;697:108667. doi: 10.1016/j.abb.2020.108667. Epub 2020 Nov 9. PMID: 33181128.
2. Saurus P, Tolvanen TA, Lindfors S, Kuusela S, Holthöfer H, Lehtonen E, Lehtonen S. Inhibition of SHIP2 in CD2AP-deficient podocytes ameliorates reactive oxygen species generation but aggravates apoptosis. Sci Rep. 2017 Sep 6;7(1):10731. doi: 10.1038/s41598-017-10512-w. PMID: 28878342; PMCID: PMC5587593.
3. Tsuneki H, Yoshida H, Okamoto K, Yamaguchi M, Endo K, Nakano A, Tsuda M, Toyooka N, Wada T, Sasaoka T. AS1949490, an inhibitor of 5'-lipid phosphatase SHIP2, promotes protein kinase C-dependent stabilization of brain-derived neurotrophic factor mRNA in cultured cortical neurons. Eur J Pharmacol. 2019 May 15;851:69-79. doi: 10.1016/j.ejphar.2019.02.003. Epub 2019 Feb 10. PMID: 30753865.
4. Suwa A, Yamamoto T, Sawada A, Minoura K, Hosogai N, Tahara A, Kurama T, Shimokawa T, Aramori I. Discovery and functional characterization of a novel small molecule inhibitor of the intracellular phosphatase, SHIP2. Br J Pharmacol. 2009 Oct;158(3):879-87. doi: 10.1111/j.1476-5381.2009.00358.x. Epub 2009 Aug 19. PMID: 19694723; PMCID: PMC2765606.
In vitro protocol:
1. Azzi A. Scaffold dependent role of the inositol 5'-phosphatase SHIP2, in regulation of oxidative stress induced apoptosis. Arch Biochem Biophys. 2021 Jan 15;697:108667. doi: 10.1016/j.abb.2020.108667. Epub 2020 Nov 9. PMID: 33181128.
2. Saurus P, Tolvanen TA, Lindfors S, Kuusela S, Holthöfer H, Lehtonen E, Lehtonen S. Inhibition of SHIP2 in CD2AP-deficient podocytes ameliorates reactive oxygen species generation but aggravates apoptosis. Sci Rep. 2017 Sep 6;7(1):10731. doi: 10.1038/s41598-017-10512-w. PMID: 28878342; PMCID: PMC5587593.
In vivo protocol:
1. Tsuneki H, Yoshida H, Okamoto K, Yamaguchi M, Endo K, Nakano A, Tsuda M, Toyooka N, Wada T, Sasaoka T. AS1949490, an inhibitor of 5'-lipid phosphatase SHIP2, promotes protein kinase C-dependent stabilization of brain-derived neurotrophic factor mRNA in cultured cortical neurons. Eur J Pharmacol. 2019 May 15;851:69-79. doi: 10.1016/j.ejphar.2019.02.003. Epub 2019 Feb 10. PMID: 30753865.
2. Suwa A, Yamamoto T, Sawada A, Minoura K, Hosogai N, Tahara A, Kurama T, Shimokawa T, Aramori I. Discovery and functional characterization of a novel small molecule inhibitor of the intracellular phosphatase, SHIP2. Br J Pharmacol. 2009 Oct;158(3):879-87. doi: 10.1111/j.1476-5381.2009.00358.x. Epub 2009 Aug 19. PMID: 19694723; PMCID: PMC2765606.
1: Ichihara Y, Fujimura R, Tsuneki H, Wada T, Okamoto K, Gouda H, Hirono S, Sugimoto K, Matsuya Y, Sasaoka T, Toyooka N. Rational design and synthesis of 4-substituted 2-pyridin-2-ylamides with inhibitory effects on SH2 domain-containing inositol 5'-phosphatase 2 (SHIP2). Eur J Med Chem. 2013 Apr;62:649-60. doi: 10.1016/j.ejmech.2013.01.014. PubMed PMID: 23434638.
2: Suwa A, Yamamoto T, Sawada A, Minoura K, Hosogai N, Tahara A, Kurama T, Shimokawa T, Aramori I. Discovery and functional characterization of a novel small molecule inhibitor of the intracellular phosphatase, SHIP2. Br J Pharmacol. 2009 Oct;158(3):879-87. doi: 10.1111/j.1476-5381.2009.00358.x. PubMed PMID: 19694723; PubMed Central PMCID: PMC2765606.
