NVP-TAE 226
作者：齊岳
發(fā)布時間：2023-08-24
09:17:21
點擊數(shù)：
產(chǎn)品名稱：NVP-TAE 226
產(chǎn)品描述：
| 產(chǎn)品描述 | NVP-TAE226 is an effective FAK inhibitor (IC50: 5.5 nM) and most effective to Pyk2(IC50: 3.5 nM); 10- to 100-fold less effective against IGF-1R, InsR, c-Met, and ALK. |
| 靶點活性 | FAK:5.5 nM, PYK2:3.5 nM |
| 體外活性 | 在體內(nèi)模型中,NVP-TAE226（100 mg/kg,p.o.）對MIA PaCa-2人胰腺腫瘤生長具有顯著抑制效果,但不影響體重.在體內(nèi)模型中,NVP-TAE226劑量依賴性地抑制4T1小鼠乳腺瘤生長和肺轉(zhuǎn)移,這與Y397上FAK的自磷酸化和絲氨酸473上Akt磷酸化的抑制相關(guān).NVP-TAE226（75 mg/kg）使負荷顱內(nèi)膠質(zhì)瘤異種移植小鼠的存活率顯著增加.在人結(jié)腸癌SCID小鼠模型中,NVP-TAE226（100 mg/kg,p.o.）使微血管密度顯著降低. |
| 體內(nèi)活性 | NVP-TAE226（0.1-10 μM）對HMEC1細胞的微管形成具有抑制作用。在血清饑餓的U87細胞中,NVP-TAE226（<1 μM）抑制細胞外基質(zhì)誘導的FAK(Tyr397)自身磷酸化。在U87和U251細胞中,NVP-TAE226（<1 μM）也會抑制IGF-I-誘導的IGF-1R磷酸化及其下游靶點基因活性（如MAPK 和Akt）。在體外膠質(zhì)瘤細胞系人工基底膜侵襲實驗中,與對照組相比, NVP-TAE226（1 μM）對腫瘤細胞侵襲具有抑制效果（>50%）。在caspase-3/7活化和poly(ADP-ribose)聚合酶裂解以及膜聯(lián)蛋白V凋亡試驗中,NVP-TAE226（1 μM）對膠質(zhì)瘤細胞系,包括野生型p53,僅表現(xiàn)出G(2)-M期阻滯,但負荷突變體p53的膠質(zhì)瘤細胞則會出現(xiàn)細胞凋亡。在人成神經(jīng)細胞瘤細胞系SK-N-AS中, NVP-TAE226（5 μM）抑制FAK磷酸化。在人成神經(jīng)細胞瘤細胞系SK-N-AS中,NVP-TAE226（<10 μM）的治療會使細胞活性降低,細胞周期阻滯,以及細胞凋亡增加。在U87和U251細胞中,NVP-TAE226（<10 μM）阻礙腫瘤細胞生長,并減弱G(2)-M細胞周期進程,這與細胞周期素B1和磷酸化cdc2(Tyr15)蛋白質(zhì)表達的減少相關(guān)。 |
| 激酶實驗 | Kinase assay: Kinase activities are assayed in Buffer A or C at 30°C, at a final ATP concentration of 15 μM. Blank values are subtracted and activities calculated as pmoles of phosphate incorporated during a 10 min incubation. Controls are performed with appropriate dilutions of dimethylsulfoxide. In a few cases phosphorylation of the substrate is assessed by autoradiography after SDS-PAGE. GSK-3α/β is purified from porcine brain by affinity chromatography on immobilized axin. It is assayed, following a 1/100 dilution in 1 mg BSA/ml 10 mM DTT, with 5 μl 40 μM GS-1 peptide, a specific GSK-3 substrate, (YRRAAVPPSPSLSRHSSPHQSpEDEEE), in buffer A, in the presence of 15 μM [γ-32P] ATP (3,000 Ci/mmol; 1 mCi/ml) in a final volume of 30 μl. After 30 min incubation at 30°C, 25 μl aliquots of supernatant are spotted onto 2.5 × 3 cm pieces of Whatman P81 phosphocellulose paper, and 20 seconds later, the filters are washed five times (for at least 5 min each time) in a solution of 10 ml phosphoric acid/liter of water. The wet filters are counted in the presence of 1 ml ACS scintillation fluid. |
| 細胞實驗 | Cell cultures are harvested with 0.05% trypsin and seeded in triplicate at 2 × 104 in 24-well culture plates for 24 h before drug treatment. Culture medium is used for mock treatment. Cells are harvested at the indicated day after treatment, and viable cells are counted using the Vi-cell viability analyze(Only for Reference) |
| 別名 | TAE226 |
| 分子量 | 468.94 |
| 分子式 | C23H25ClN6O3 |
| CAS No. | 761437-28-9 |
存儲
Powder: -20°C for 3 years | In solvent: -80°C for 2 years
溶解度
DMSO: 87 mg/mL (185.5 mM)
Ethanol: <1 mg/mL
H2O: <1 mg/mL
( < 1 mg/mL refers to the product slightly soluble or insoluble )
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