| CAS |
No.1159824-67-5 |
| 英文名称 |
CZC-24832 |
| 别名 |
;CS-0710;FD5029; |
| 分子式 |
C15H17FN6O2S |
| 分子量 |
364.4 |
| 溶解性 |
Soluble in DMSO ≥1mg/mL(Need ultrasonic) |
| 纯度 |
≥98% |
| 外观(性状) |
White to off-white Solid |
| 储存条件 |
Powder:2-8℃，2 years;Insolvent(母液):-20℃，6 months;-80℃，1 year |
| EC |
EINECS 200-258-5 |
| MDL |
MFCD22417090 |
| SMILES |
FC1=CC(C2=CC(S(=O)(NC(C)(C)C)=O)=CN=C2)=CN3C1=NC(N)=N3 |
| InChIKey |
RXRZPHQBTHQXSV-UHFFFAOYSA-N |
| InChI |
InChI=1S/C15H17FN6O2S/c1-15(2,3)21-25(23,24)11-4-9(6-18-7-11)10-5-12(16)13-19-14(17)20-22(13)8-10/h4-8,21H,1-3H3,(H2,17,20) |
| PubChem CID |
42623951 |
| 靶点 |
PI3K |
| 通路 |
PI3K/Akt/mTOR |
| 背景说明 |
是一种有效的选择性 PI3Kγ 抑制剂。 |
| 生物活性 |
CZC24832 is a highly selective and potent PI3Kγ inhibitor (IC50=27 nM) with apparent dissociation constants (Kdapp) of 19 nM.[1] |
| In Vitro |
CZC24832 is active in PI3Kγ-dependent cellular C5a-induced AKT Ser473 phosphorylation (IC50=1.2 μM) and N-formyl-methionine-leucinephenylalanine (fMLP)-induced neutrophil migration assays (IC50=1.0 μM)[1]. |
| In Vivo |
CZC24832 shows suitable pharmacokinetic properties including low clearance (0.84 L per h per kg body weight) and high oral bioavailability (37%)， thus allowing further characterization of the inhibitor in rodent models of inflammation. In an IL-8-dependent air pouch model， CZC24832 shows a dose-dependent reduction of granulocyte recruitment (80% inhibition at 10 mg per kg body weight) consistent with the degree of inhibition observed in PI3Kγ-null mice. Mice treated orally with 10 mg CZC24832 per kg body weight twice per day show a substantial decrease of bone and cartilage destruction (53% reduction by histopathological analysis) as well as of overall clinical parameters (38% reduction)[1]. |
| 细胞实验 |
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]. |
| 动物实验 |
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. |
| 数据来源文献 |
[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. |
| 规格 |
1mg 5mg 10mg 25mg 50mg |
| 单位 |
瓶 |
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英语
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