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PF-4989216
本产品不向个人销售，仅用作科学研究，不用于任何人体实验及非科研性质的动物实验。
PF-4989216图片
CAS NO:1276553-09-3
规格:≥98%
包装与价格：
包装价格(元)
5mg电议
25mg电议
50mg电议
100mg电议
250mg电议
500mg电议

产品介绍
理化性质和储存条件

Molecular Weight (MW)

380.4

Formula

C18H13FN6OS

CAS No.

1276553-09-3

Storage

-20℃ for 3 years in powder form

-80℃ for 2 years in solvent

Solubility (In vitro)

DMSO: 76 mg/mL (199.8 mM)

Water:<1 mg/mL

Ethanol: 7 mg/mL warming (18.4 mM)

Solubility (In vivo)

Suspended in 0.5% methylcellulose: 1mg/mL

Chemical Name / Synonym

4-(4-cyano-2-fluorophenyl)-2-morpholino-5-(1H-1,2,4-triazol-3-yl)thiophene-3-carbonitrile; PF4989216; PF 4989216; PF-4989216

实验参考方法
In VitroKinase Assay: PF-4989216 (Compound 10) has excellent PI3Kα Ki (0.6 nM), good cellular potency (S473 IC50=79 nM), and good selectivity against mTOR (mTOR Ki=1440 nM). PF-4989216 has PI3Kα Ki less than 1 nM and mTOR Ki more than 1 μM. PF-4989216 also has excellent selectivity over 40 other kinases, and no major CYP inhibitions are observed. Less than 30% inhibition is observed in 1A2, 2C9, 2D6, and 3A4 CYP enzymes at 3 μM.

Cell Assay: SCLC cells are cultured (5,000 cells/well) in a 96-well microtiter plate at 37°C in 5% CO2 in supplier-recommended growth media and compounds are added to each well starting at 10 μM with a 3-fold serial dilution. At 72 hours after compound addition, CellTiter-Glo (CTG) Solution is added per the manufacturer's instructions. Luminescence is read on an Envision plate reader. All experiments are run in duplicate and have been repeated at least three times. Cells NCI-H69, NCI-H1048, NCI-H1436, NCI-H82, NCI-H254, NCI-H526, NCI-H1963, NCI-H146, NCI-H841, Lu99A, Lu134B, and Lu134A cells.

PF-4989216 significantly inhibits cell viability in SCLC cells with a PIK3CA mutation, such as NCI-H69, NCI-H1048, and Lu99A cells. PF-4989216, via PI3K signaling inhibition, blocks cell-cycle progression and reduces cell transformation in SCLCs. In SCLCs with PIK3CA mutation, PF-4989216 induces BIM-mediated apoptosis.

In VivoIn SCID mice bearing NCI-H69 or NCI-H1048 xenograft tumors, PF-4989216 (350 mg/kg, p.o.) inhibits PI3K phosphorylation signaling and induces antitumor activity.
Animal modelSCID mice bearing NCI-H69 or NCI-H1048 xenograft tumors
Formulation & DosageDissolved in in 0.5% methylcellulose; 350 mg/kg; oral administration
References[1] Walls M, et al. Clin Cancer Res. 2014, 20(3), 631-643.
生物活性


PF-4989216 inhibited PI3K downstream signaling in SCLC cells. Clin Cancer Res. 2014, 20(3), 631-643.





PF-4989216 inhibited PI3K phosphorylation signaling and induced antitumor activity in NCI-H1048 xenograft models. Clin Cancer Res. 2014, 20(3), 631-643.


PF-4989216 inhibited PI3K phosphorylation signaling and induced antitumor activity in NCI-H1048 xenograft models. Clin Cancer Res. 2014, 20(3), 631-643.