Powder: -20°C for 3 years | In solvent: -80°C for 1 year
CHIR-99021 (CT99021) is an activator of the Wnt/β-catenin signaling pathway and a GSK-3α/β inhibitor (IC50=10/6.7 nM) with selective and oral activity.CHIR-99021 induces cellular autophagy, which enhances self-renewal in mouse and human embryonic stem cells.
パッケージサイズ | 在庫状況 | 単価(税別) | キャンペーン価格 | ||
---|---|---|---|---|---|
無料サンプル 1 mg | |||||
2 mg | 在庫あり | ¥ 9,500 | ¥ 8,000 | ||
5 mg | 在庫あり | ¥ 14,000 | ¥ 11,500 | ||
10 mg | 在庫あり | ¥ 20,500 | ¥ 16,500 | ||
25 mg | 在庫あり | ¥ 40,000 | ¥ 32,000 | ||
50 mg | 在庫あり | ¥ 62,000 | ¥ 50,000 | ||
100 mg | 在庫あり | ¥ 98,500 | ¥ 79,000 | ||
1 mL * 10 mM (in DMSO) | 在庫あり | ¥ 15,000 | ¥ 12,000 |
説明 | CHIR-99021 (CT99021) is an activator of the Wnt/β-catenin signaling pathway and a GSK-3α/β inhibitor (IC50=10/6.7 nM) with selective and oral activity.CHIR-99021 induces cellular autophagy, which enhances self-renewal in mouse and human embryonic stem cells. |
ターゲット&IC50 | GSK-3α:10 nM (cell free), GSK-3β:6.7 nM (cell free) |
In vitro |
METHODS: Mouse stem cells ES-D3 were treated with CHIR-99021 (1-10 µM) for 72 h. Cell growth inhibition was detected using MTT. RESULTS: CHIR-99021 dose-dependently inhibited ES-D3 cell growth with an IC50 of 4.9 µM.[1] METHODS: Mouse embryonic stem cells J1 mESCs and mouse embryoma cells F9 mEC were treated with CHIR-99021 (3 μM) for 24 h. The expression levels of target proteins were detected by immunofluorescence. RESULTS: After CHIR-99021 treatment, β-linker proteins were increased in the cytoplasm and nucleus of J1-mESCs and F9-mEC cells. [2] METHODS: Human Tenon fibroblast HTFs were treated with CHIR-99021 (5 μM) for 48 h, and the expression levels of target proteins were detected by Western Blot. RESULTS: The production of the active form of GSK-3β (p-GSK-3β (Y216)) was significantly reduced by CHIR-99021 treatment. [3] |
In vivo |
METHODS: To test the antitumor activity in vivo, CHIR-99021 (37.5 mg/kg/twice daily on days 0-3, 6-10, 13-17, and 20) was orally administered and paclitaxel (10 mg/kg/one dose on day 0) was intraperitoneally injected into Balb/c nude mice harboring human non-small cell lung cancer tumor H1975. RESULTS: CHIR-99021 and paclitaxel synergistically inhibited NSCLC tumor growth in vivo. [4] METHODS: To investigate whether direct pharmacological inhibition of GSK-3 alters the positive potentiation of alcohol in mice, CHIR-99021 (1-10 mg/kg) was administered by single intraperitoneal injection to C57BL/6J mice with a history of alcohol or sucrose self-administration. RESULTS: CHIR-99021 dose-dependently increased alcohol-enhanced responses with no effect on sucrose self-administration or locomotor activity. ChIR-99021 significantly decreased pGSK-3β expression in all brain regions tested, decreased PICK1 and increased total GluA2 expression only in NAcb. [5] |
キナーゼ試験 | Kinases were purified from SF9 cells through the use of their His or Glu tag. Glu-tagged proteins were purified as described, and His-tagged proteins were purified according to the manufacturer's instructions. Kinase assays were performed in 96-well plates with appropriate peptide substrates in a 300-μl reaction buffer (variations on 50 mM Tris-HCl, pH 7.5, 10 mM MgCl2, 1 mM EGTA, 1 mM dithiothreitol, 25 mMβ-glycerophosphate, 1 mM NaF, and 0.01% bovine serum albumin). Peptides had Km values from 1 to 100 μM. CHIR 99021 or CHIR GSKIA was added in 3.5 μl of Me2SO, followed by ATP to a final concentration of 1 μM. After incubation, triplicate 100-μl aliquots were transferred to Combiplate 8 plates containing 100 μl/well of 50 μM ATP and 20 mM EDTA. After 1 hour, the wells were rinsed five times with phosphate-buffered saline, filled with 200 μl of scintillation fluid, sealed, and counted in a scintillation counter 30 min later. All of the steps were at room temperature. The percentage of inhibition was calculated as 100 × (inhibitor ? no enzyme control)/(Me2SO control ? no enzyme control) [4]. |
細胞研究 | The Wnt/beta-catenin reporter assay was performed with the M50 Super 8× TOPFlash and M51 Super 8× FOPFlash vector containing the firefly luciferase gene under the control of TCF/LEF binding sites or mutated bindings sites. 12,500 cells were seeded overnight on gelatine-coated 96-well plates in LIF-containing ES cell medium. On the next day, the cells were transfected using Lipofectamine with one of the aforementioned vectors plus pGL4.75 [hRluc/CMV] encoding the renilla luciferase reporter gene hRluc as a transfection control. Six hours after transfection the medium was changed to medium devoid of LIF, with reduced serum, and supplemented with 5 μM CHIR-99021. The Dual-Luciferase? reporter assay system was employed 48 and 72 h after the medium change to follow the luminescence reaction using a GloMax?-multi detection system [4]. |
動物実験 | Blood was obtained by shallow tail snipping at lidocaine-anesthetized tips. Blood glucose was measured directly or heparinized plasma was collected for measurement of glucose or insulin. Animals were pre-bled and randomized to vehicle control or GSK-3 inhibitor treatment groups. For glucose tolerance tests (GTTs), animals fasted throughout the procedure with food removal early in the morning, 3 h before the first prebleed (db/db mice), or the previous night, 16 h before the bleed (ZDF rats). When the time course of plasma glucose and insulin changes in fasting ZDF rats was measured, food was removed ~16 h before test agent administration. The glucose challenges in the GTT were 1.35 g/kg i.p. (ipGTT) or 2 g/kg via oral gavage (oGTT). CHIR-99021 were formulated as solutions in 20 mmol/l citrate-buffered 15% Captisol or as fine suspensions in 0.5% carboxymethylcellulose [1]. |
別名 | Laduviglusib, CT99021, CHIR-99021 |
分子量 | 465.34 |
分子式 | C22H18Cl2N8 |
CAS No. | 252917-06-9 |
Powder: -20°C for 3 years | In solvent: -80°C for 1 year
DMSO: 9.3 mg/mL (20 mM)
You can also refer to dose conversion for different animals. 詳細
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CHIR-99021 252917-06-9 Autophagy Cytoskeletal Signaling PI3K/Akt/mTOR signaling Stem Cells GSK-3 Wnt/beta-catenin Glycogen synthase kinase 3 CHIR99021 β-catenin Laduviglusib inhibit CT99021 Beta catenin CT-99021 CHIR 99021 Wnt Inhibitor Glycogen synthase kinase-3 CT 99021 inhibitor