919486-40-1
919486-40-1 structure
- Name: AS1517499
- Chemical Name: 4-(benzylamino)-2-[2-(3-chloro-4-hydroxyphenyl)ethylamino]pyrimidine-5-carboxamide
- CAS Number: 919486-40-1
- Molecular Formula: C20H20ClN5O2
- Molecular Weight: 397.85800
- Catalog: Signaling Pathways JAK/STAT Signaling STAT
- Create Date: 2018-12-29 19:05:14
- Modify Date: 2024-01-02 19:18:01
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AS1517499 is a potent STAT6 inhibitor with an IC50 of 21 nM.
| Name | 4-(benzylamino)-2-[2-(3-chloro-4-hydroxyphenyl)ethylamino]pyrimidine-5-carboxamide |
|---|---|
| Synonyms |
unii-2h31hot08t
AS1517499 |
| Description | AS1517499 is a potent STAT6 inhibitor with an IC50 of 21 nM. |
|---|---|
| Related Catalog | |
| Target |
STAT6:21 nM (IC50) |
| In Vitro | AS1517499 shows potent STAT6 inhibition with an IC50 value of 21 nM, and also inhibits IL-4-induced Th2 differentiation of mouse spleen T cells with an IC50 value of 2.3 nM and without influencing T-helper cell 1 (Th1) differentiation induced by IL-12. AS1517499 selectively inhibits Th2 differentiation without affecting Th1 differentiation[1]. In cultured human BSM cells, IL-13 (100 ng/mL) causes a phosphorylation of STAT6 and an up-regulation of RhoA, a monomeric GTPase responsible for Ca2+ sensitization of smooth muscle contraction: both events are inhibited by co-incubation with AS1517499 (100 nM)[2]. |
| In Vivo | In BALB/c mice that are actively sensitized and repeatedly challenged with ovalbumin antigen, an increased IL-13 level in bronchoalveolar lavage fluids and a phosphorylation of STAT6 in bronchial tissues are observed after the last antigen challenge. These mice have an augmented BSM contractility to acetylcholine together with an up-regulation of RhoA in bronchial tissues. Intraperitoneal injections of AS1517499 (10 mg/kg) 1 hour before each ovalbumin exposure inhibits both the antigen-induced up-regulation of RhoA and BSM hyperresponsiveness, almost completely[2]. |
| Cell Assay | Normal human BSM cells (hBSMCs) are maintained in SmBM medium supplemented with 5% fetal bovine serum, 0.5 ng/mL human epidermal growth factor (hEGF), 5 μg/mL insulin, 2 ng/mL human fibroblast growth factor-basic (hFGF-b), 50 μg/mL gentamicin, and 50 ng/mL amphotericin B. Cells are maintained at 37°C in a humidified atmosphere (5% CO2), fed every 48 to 72 hours, and passaged when cells reached 90 to 95% confluence. Then the hBSMCs (passages 7-9) are seeded in 6-well plates and 8-well chamber slides at a density of 3,500 cells/cm2 and, when 80 to 85% confluence observed, cells are cultured without serum for 24 hours before addition of recombin is ant human IL-13. AS1517499 (100 nM) or its vehicle (0.3% DMSO) is treated 30 minutes before the addition of IL-13 (100 ng/mL). In some experiments, AS1517499 is treated 0 (co-incubation), 3, or 12 hours after the addition of IL-13. In another series of experiments, a selective Rho-kinase inhibitor Y-27632 (1 μM) or its vehicle (0.3% DMSO) is also applied 15 minutes before the IL-13 application. At the indicated time after the IL-13 treatment, cells are washed with PBS, immediately collected, and disrupted with 1× SDS sample buffer (250 μL/well), and used for Western blot analyses[2]. |
| Animal Admin | Mice[2] Male BALB/c mice are used. Preparation of a murine model of allergic bronchial asthma, which has an in vivo AHR, is performed. In brief, BALB/c mice (8 wk of age) are actively sensitized by intraperitoneal injections of 8 μg ovalbumin (OVA) with 2 mg Imject Alum on Day 0 and Day 5. The sensitized mice are challenged with aerosolized OVA-saline solution (5 mg/mL) for 30 minutes on Days 12, 16, and 20. A control group of mice received the same immunization procedure but inhaled saline aerosol instead of OVA challenge. The aerosol is generated with an ultrasonic nebulizer and introduced to a Plexiglas chamber box (130×200 mm, 100 mm height) in which the mice are placed. Animals also received intraperitoneal injection with AS1517499 (1 or 10 mg/kg/d; dissolved in 20% DMSO in saline) or its vehicle 1 hour before each antigen inhalation (Days 12, 16, and 20). Twenty-four hours after the last OVA challenge, mice are killed by exsanguination from abdominal aorta under urethane (1.6 g/kg, intraperitoneally) anesthesia. |
| References |
| Molecular Formula | C20H20ClN5O2 |
|---|---|
| Molecular Weight | 397.85800 |
| Exact Mass | 397.13100 |
| PSA | 120.61000 |
| LogP | 2.92920 |
| Storage condition | -20℃ |