CZC24832
(Synonyms: 5-(2-氨基-8-氟[1,2,4]三唑并[1,5-A]吡啶-6-基)-N-(叔丁基)-3-吡啶磺酰胺,CZC 24832;CZC-24832) 目录号 : GC14798
A PI3Kγ inhibitor
Cas No.:1159824-67-5
Sample solution is provided at 25 µL, 10mM.
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PI3Kγ is one of four class I PI3Ks, a family of dual lipid and protein kinases involved in the regulation of numerous biological processes, such as cell growth, differentiation, survival, proliferation and migration1. A high-throughput chemoproteomics method has benen optimized to enable multiplexed screening resulting in the finding of CZC24832.
In vitro: Plenty of target- and cell-based studies of CZC24832 revealed regulation of interleukin-17–producing T helper cell (TH17) differentiation by PI3Kg, therefore giving selective inhibition of PI3Kg as a potential treatment for inflammatory and autoimmune diseases [1].
In vivo: CZC24832, the first selective inhibitor of phosphoinositide 3-kinase g (PI3Kg), was found to have efficacy in in vivo models of inflammation [1].
Clinical trial: Currenlty no clinical data are available.
Reference:
[1] Bergamini G, Bell K, Shimamura S, Werner T, Cansfield A, Müller K, Perrin J, Rau C, Ellard K, Hopf C, Doce C, Leggate D, Mangano R, Mathieson T, O'Mahony A, Plavec I, Rharbaoui F, Reinhard F, Savitski MM, Ramsden N, Hirsch E, Drewes G, Rausch O, Bantscheff M, Neubauer G. A selective inhibitor reveals PI3Kγ dependence of T(H)17 cell differentiation. Nat Chem Biol. 2012;8(6):576-82.
Cell experiment: | RAW264.7 or THP-1 cells are starved for 2.5 h in serum-free medium before CZC24832 (0.1, 1, 10 and 100 μM) incubation for 30 min at 37°C. RAW264.7 cells are then stimulated for 3 min with C5a at a concentration of 0.6 μM, and THP-1 cells are stimulated with either insulin (1 uM, 10 min) or CSF (50 μg/mL, 5 min) at 37°C and lysed on ice. The detection of AKT phosphorylation (Ser473) is performed using the iBlot system[1]. |
Animal experiment: | Rats[1]Pharmacokinetics and oral bioavailability of CZC24832 are investigated in male Wistar rats following administration of a single intravenous (0.2 mg per kg body weight) or oral dose (10 mg per kg body weight). The dosing vehicle used is 0.5% (w/v) carboxymethyl cellulose in water for oral gavage. The intravenous dosing vehicle is 10% (v/v) DMSO in 30% (v/v) polyethylene glycol (PEG-400). Heparin blood for pharmacokinetic analysis is withdrawn retro-orbitally from mice or sublingually from rats to prepare plasma samples. These are homogenized with 10% (v/v) water and 3 volumes of acetonitrile and analyzed for CZC24832 by HPLC-MS/MS. |
References: [1]. Bergamini G, et al. A selective inhibitor reveals PI3Kγ dependence of T(H)17 cell differentiation. Nat Chem Biol. 2012 Apr 29;8(6):576-82. | |
| Cas No. | 1159824-67-5 | SDF | |
| 别名 | 5-(2-氨基-8-氟[1,2,4]三唑并[1,5-A]吡啶-6-基)-N-(叔丁基)-3-吡啶磺酰胺,CZC 24832;CZC-24832 | ||
| 化学名 | 5-(2-amino-8-fluoro-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-N-tert-butylpyridine-3-sulfonamide | ||
| Canonical SMILES | CC(C)(C)NS(=O)(=O)C1=CN=CC(=C1)C2=CN3C(=NC(=N3)N)C(=C2)F | ||
| 分子式 | C15H17FN6O2S | 分子量 | 364.4 |
| 溶解度 | ≥ 6.07 mg/mL in DMSO with gentle warming | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.7442 mL | 13.7212 mL | 27.4424 mL |
| 5 mM | 0.5488 mL | 2.7442 mL | 5.4885 mL |
| 10 mM | 0.2744 mL | 1.3721 mL | 2.7442 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet