4-[(4-chlorophenyl)methyl]-1-{7H-pyrrolo[2,3-d]pyrimidin-4-yl}piperidin-4-amine

• ChemBase编号: 73118
• 分子式: C18H20ClN5
• 平均质量: 341.8379
• 单一同位素质量: 341.14072335
• SMILES: n1cnc2c(c1N1CCC(CC1)(N)Cc1ccc(cc1)Cl)cc[nH]2
• Canonical SMILES: Clc1ccc(cc1)CC1(N)CCN(CC1)c1ncnc2c1cc[nH]2
• InChI: InChI=1S/C18H20ClN5/c19-14-3-1-13(2-4-14)11-18(20)6-9-24(10-7-18)17-15-5-8-21-16(15)22-12-23-17/h1-5,8,12H,6-7,9-11,20H2,(H,21,22,23)
• InChIKey: RZIDZIGAXXNODG-UHFFFAOYSA-N

名称和登记号

名称

• IUPAC标准名: 4-[(4-chlorophenyl)methyl]-1-{7H-pyrrolo[2,3-d]pyrimidin-4-yl}piperidin-4-amine
• IUPAC传统名: 4-[(4-chlorophenyl)methyl]-1-{7H-pyrrolo[2,3-d]pyrimidin-4-yl}piperidin-4-amine
• 别名: CCT 128930; CCT-128930; CCT128930

登记号

• CAS号: 1166227-08-2
• PubChem SID: 162038038
• PubChem CID: 17751819

理论计算性质

• 质子供体: 2
• LogD (pH = 5.5): -1.5442048
• LogD (pH = 7.4): 0.40335903
• Log P: 2.9705863
• 摩尔折射率: 97.9473 cm^3
• 极化性: 37.441536 Å^3
• 极化表面积: 70.83 Å^2
• 可自由旋转的化学键: 3
• 里宾斯基五规则: true
• Acid pKa: 13.590311
• 质子受体: 4

分子性质

安全信息

• 保存条件: -20°C

药理学性质

• 作用靶点: Akt

产品相关信息

• 成盐信息: Free Base

详细说明

Selleck Chemicals - S2635

Research Area

• Description: Cancer

Biological Activity

• Description: CCT128930 is a potent, ATP-competitive and selective inhibitor of Akt2 with IC50 of 6 nM.
• Targets: Akt2; PKA; p70S6K
• IC50: 6 nM; 168 nM; 120 nM ^[1]
• In Vitro: CCT128930 exhibits marked antiproliferative activity against PTEN-deficient human tumor cell lines including U87MG human glioblastoma cells, LNCaP human prostate cancer cells and PC3 human prostate cancer cells with GI50 of 6.3 μM, 0.35 μM and 1.9 μM, respectively. Furthermore, CCT128930 causes a G1 arrest in PTEN-null U87MG human glioblastoma cells and Akt pathway blockade. ^[1]
• In Vivo: CCT128930 at 25 mg/kg i.p. shows a marked antitumor effect in established PTEN-null U87MG human glioblastoma xenografts with a treated:control (T/C) ratio of 48% on day 12. In HER2-positive, PIK3CA-mutant BT474 human breast cancer xenografts, CCT128930 at 40 mg/kg also produces a profound antitumor effect with complete growth arrest and a T/C ratio of 29% on day 22. CCT128930 administrated via i.v. reaches a peak concentration of 6.4 μM in plasma and was eliminated with a relatively short half-life, high volume of distribution, and rapid clearance, giving an area under the curve AUC_0-∞ of 4.6 μM h. CCT128930 administrated via i.p. leads to the peak plasma drug concentration of 1.3 μM and the corresponding AUC_0-∞ of 1.3 μM·h. Oral CCT128930 administration leads to the peak plasma concentration of only 0.43 μM and a correspondingly low AUC_0-∞ of 0.4 μM·h. ^[1]

Protocol

• Protocol: Kinase Assay ^[1]
• Kinase assays: Profiling against 50 different human kinases was carried out using 10 μM CCT128930 at an ATP concentration equivalent to the K_m for each enzyme.
• Protocol: Cell Assay ^[1]
• Cell Lines: U87MG, LNCaP and PC3 cells
• Concentrations: 0-18.9 μM
• Incubation Time: 48 hours
• Methods: Cells are seeded in 96-well plates and allowed to attach for 36 hours to ensure exponential growth prior to treatment. In vitro antiproliferative activity is determined using a 96-hour SRB assay. TCA-fixed cells are stained for 30 minutes with 0.4% (wt/vol) SRB dissolved in 1% acetic acid. At the end of the staining period, SRB is removed and cultures are quickly rinsed four times with 1% acetic acid to remove unbound dye. The acetic acid is poured directly into the culture wells from a beaker. This procedure permits rinsing to be performed quickly so that desorption of protein-bound dye does not occur. Residual wash solution is removed by sharply flicking plates over a sink, which ensures the complete removal of rinsing solution. Because of the strong capillary action in 96-well plates, draining by gravity alone often fails to remove the rinse solution when plates are simply inverted. After being rinsed, the cultures are air dried until no standing moisture is visible. Bound dye is solubilized with 10 mM unbuffered Tris base (pH 10.5) for 5 minutes on a gyratory shaker. OD is read in either a UVmax microtiter plate reader or a Beckman DU-70 spectrophotometer. For maximum sensitivity, OD is measured at 564 nm. Because readings are linear with dye concentrations only below 1.8 OD units, however, suboptimal wavelengths are generally used, so that all samples in an experiment remains within the linear OD range. With most cell lines, wavelengths of approximately 490-530 nm works well for this purpose.
• Protocol: Animal Study ^[1]
• Animal Models: PTEN-null U87MG human glioblastoma cells are injected subcutaneously (s.c.) in the right flank of female CrTacNCr-Fox1nu mice. For HER2-positive, PIK3CA-mutant BT474 human breast cancer xenografts, cells are administered s.c. in medium supplemented with Matrigel (1:1) into the mammary fat pads of female mice implanted s.c. with estradiol pellets.
• Formulation: CCT128930 is dissolved in 10% DMSO, 5% Tween 20, and 85% saline.
• Doses: ≤50 mg/kg
• Administration: Administered via i.p.

References

• References: [1] Yap TA, et al. Mol Cancer Ther. 2011, 10(2), 360-371.

参考文献

• Yap TA, et al. Mol Cancer Ther. 2011, 10(2), 360-371.