PF-AKT400 - CAS:1004990-28-6 - CAS号查询_生物试剂_化学试剂_分析试剂

中文名称:	PF-AKT400
英文名称:	PF-AKT400
别名:	(S)-N-[[3-氨基-1-(5-乙基-7H-吡咯并[2,3-d]嘧啶-4-基)吡咯烷-3-基]甲基]-2,4-二氟苯甲酰胺;(S)-N-[[3-氨基-1-(5-乙基-7H-吡咯并[2,3-D]嘧啶-4-基)吡咯烷-3-基]甲基]-2,4-二氟苯甲酰胺 AKT protein kinase inhibitor;N-{[(3s)-3-Amino-1-(5-Ethyl-7h-Pyrrolo[2,3-D]pyrimidin-4-Yl)pyrrolidin-3-Yl]methyl}-2,4-Difluorobenzamide
CAS No:	1004990-28-6	分子式:	C₂₀H₂₂F₂N₆O	分子量:	400.43
CAS No:	1004990-28-6
分子式:	C₂₀H₂₂F₂N₆O
分子量:	400.43

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P11734 PF-AKT400 ≥95% (psaitong)

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包装规格：

5mg 10mg 50mg 100mg in glass bottle

溶解性：

溶于DMSO(≥100mg/mL）

产品描述：

基本信息

产品编号：	P11734
产品名称：	PF-AKT400
CAS:	1004990-28-6	储存条件	粉末	-20℃	四年

分子式：	C20H22F2N6O		溶于液体	-80℃	6个月
分子量：	400.43			-20℃	1个月
化学名：	AKT protein kinase inhibitor;N-{[(3s)-3-Amino-1-(5-Ethyl-7h-Pyrrolo[2,3-D]pyrimidin-4-Yl)pyrrolidin-3-Yl]methyl}-2,4-Difluorobenzamide
Solubility (25°C)：
体外:	DMSO
	Ethanol
	Water
体内(现配现用):
＜1mg/ml表示微溶或不溶。
普西唐提供的所有化合物浓度为内部测试所得，实际溶液度可能与公布值有所偏差，属于正常的批间细微差异现象。
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。

制备储备液

浓度溶液体积质量	1mg	5mg	10mg
1mM	2.4973mL	12.4866mL	24.9732mL
5mM	0.4995mL	2.4973mL	4.9946mL
10mM	0.2497mL	1.2487mL	2.4973mL

生物活性

产品描述	一种有效的,ATP竞争性的选择性Akt抑制剂，对PKBα(IC50=0.5nM)的选择性比PKA (IC50=450nM)高900倍。
靶点	PKBα 0.5nM (IC50)	PKA 450nM (IC50)
体外研究	PF-AKT400 (Compound 42) provides significantly enhanced selectivity for Akt relative to earlier leads such as spiroindoline 2.Free IC50 and EC50 values are estimated for phospho-S6 reduction (110nM) and Akt hyperphosphorylation (216nM),respectively.These values corresponded well to the cellular IC50 for PF-AKT400 in U87 cells measuring p-GSK-3α(310nM).
体内研究	PF-AKT400 is subsequently evaluated for modulation of Akt in tumors and in multiple in vivo mouse models of antitumor efficacy.It is active in a PC3 prostate carcinoma xenograft experiment,with 75% TGI observed at 100mg/kg b.i.d.dosing for 10 days.In a colorectal carcinoma (Colo205) xenograft study,PF-AKT400 produces 60% TGI at 150mg/kg b.i.d.after 10 days.Most intriguingly,in combination with Rapamycin (10mg/kg,ip),75mg/kg b.i.d.(10 days) of PF-AKT400 results in 98% TGI in an additional PC3 prostate carcinoma xenograft study compared to 56% TGI and 66% TGI with PF-AKT400 and Rapamycin as single agents.To define the in vivo potency of PF-AKT400 (Compound 42) in the PC3 xenograft model, oral administration of 25,75,and 100mg/kg PF-AKT400 is performed with blood and tumor sampling over time.Immunoblot analysis of detergentsoluble extracts derived from PC3 tumors shows a significant reduction of S6 phosphorylation,and hyperphosphorylation of Akt upon treatment at doses that produced significant tumor growth inhibition.Plasma drug concentrations peak rapidly after oral administration of doses between 25-100mg/kg (Tmax=0.5h).Peak PD responses of phospho-S6 and phospho-Akt are observed at approximately 2-4h and 1h post-administration of PF-AKT400,respectively.The time-course of PD marker response is well described by a PK/PD model at doses that ranged from no efficacy (25mg/kg) to maximal efficacy (100mg/kg).

推荐实验方法(仅供参考)

激酶实验：

A fluorescence polarization IMAP type assay is used. An amount of 15μL of diluted PF-AKT400 (Compound 42) in DMSO is mixed with 60μL of reaction buffer (10mM Tris-HCl,pH 7.5,10mM MgCl2,0.1mM EGTA,0.01% Triton-X100,1mM DTT).Then 5μL of the compound/buffer mixture,10μL of a solution containing 4μM ATP and 40nM fluorescent-labeled Crosstide (Tamara-labeled GRPRTSSFAEG peptide),and 5μL of Akt1 protein (lacking the pleckstrin homology (PH) domain,containing an Asp at position 473,and prephosphorylated at Thr 308) in reaction buffer are combined.After a 90 min incubation,IMAP beads are added and plates are read (lamp filter,544nm;emission filter,615nm).The same procedure can be applied to full length Akt1 to provide similar results. All IC50 values are the geometric mean of at least n=2 determinations.

动物实验:

Mice

Studies to describe the PK/PD relationship for PF-AKT400 are performed in male SCID/Beige mice bearing subcutaneous PC3 prostate carcinoma xenografts.Once tumors reach about ~300mm3 in size,PF-AKT400 is formulated in 0.5% methylcellulose vehicle and administered orally to 3 mice per dose group.Plasma and tumors are harvested over time,tumor lysates prepared,and the levels of phospho S6 reduction and phospho Akt induction are evaluated by immunoblot.

保存条件：

-20℃

UN码：

HazardClass：

危害声明：

安全说明：

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参考文献 & 客户发表文献

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质量 (g) = 浓度 (mol/L) x 体积 (L) x 分子量 (g/mol)

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质量 =

浓度 *

体积 *

分子量

*选择对应的单位 *空出希望得到的变量，填写另外两个变量

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* = *

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C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):

摩尔浓度计算公式

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