1. PI3K/Akt/mTOR
  2. PI3K
  3. AMG319

AMG319 

製品番号: HY-12948 純度: 98.40%
取扱説明書

AMG319 is a potent and selective PI3Kδ kinase inhibitor with IC50 of 18 nM.

商品は「研究用試薬」です。人や動物の医療用・臨床診断用・食品用としては使用しないように、十分ご注意ください。

AMG319 構造式

AMG319 構造式

CAS 番号 : 1608125-21-8

容量 価格(税別) 在庫状況 数量
無料サンプル (0.5-1 mg)   今すぐ申し込む  
10 mM * 1  mL in DMSO USD 132 在庫あり
Estimated Time of Arrival: December 31
5 mg USD 120 在庫あり
Estimated Time of Arrival: December 31
10 mg USD 216 在庫あり
Estimated Time of Arrival: December 31
50 mg USD 648 在庫あり
Estimated Time of Arrival: December 31
100 mg USD 960 在庫あり
Estimated Time of Arrival: December 31
200 mg   お問い合わせ  
500 mg   お問い合わせ  

* アイテムを追加する前、数量をご選択ください

カスタマーレビュー

Based on 1 publication(s) in Google Scholar

Top Publications Citing Use of Products
  • 生物活性

  • プロトコル

  • 純度とドキュメンテーション

  • 参考文献

  • カスタマーレビュー

製品説明

AMG319 is a potent and selective PI3Kδ kinase inhibitor with IC50 of 18 nM.

IC50 & Target[1]

PI3Kδ

18 nM (IC50)

PI3Kγ

850 nM (IC50)

PI3Kβ

2.7 μM (IC50)

PI3Kα

33 μM (IC50)

体外実験

AMG319 inhibits PI3Kδ, PI3Kγ, PI3Kβ and PI3Kα with IC50s of 18 nM, 850 nM, 2.7 μM and 33 μM, respectively. AMG319, a compound with an IC50 of 16 nM in a human whole blood assay (HWB), excellent selectivity over a large panel of protein kinases, and a high level of in vivo efficacy as measured by two rodent disease models of inflammation. AMG319 has minimal CYP3A4/2D6 inhibition and does not inhibit CYPs (1A2, 2C8, 2C9, 2C19, 2E1, all >20 μM). There is no time dependent inhibition (TDI) against CYPs 3A4, 2D6, 1A2, and 2C9 nor CYP induction (3A4, 2D6, 1A2, 2B6) as measured in hepatocytes. AMG319 is clean in a hERG binding assay (>25 μM), and an Ames micronucleus test proved negative. AMG319 has minimal effects in a BSEP assay up to >200 μM. Additionally, AMG319 is clean in a large side effect profiling panel (CEREP) and has no activity in a large panel of 359 unique protein kinases tested at 10 μM drug concentration[1].

体内実験

The study is performed to determine the correlation between biochemical coverage (i.e., pAKT) with functional activity in vivo. AMG319 achieves this coverage at the 3 mg/kg level, which also coveres the human whole blood assay (HWB) (CD-69) IC90 at trough for a full 24 h period. The lower doses 0.1, 0.3, and 1 mg/kg cover trough concentrations between the HWB IC50 and IC90 and evince partial efficacy. Similarly, the plasma concentration of AMG319 covers the IC90 at the 1 mg/kg dose of the mouse anti-IgM pAKT in vitro assay[1].

臨床実験
分子量

385.40

分子式

C₂₁H₁₆FN₇

CAS 番号

1608125-21-8

SMILES

C[[email protected]](NC1=C2N=CNC2=NC=N1)C3=CC4=CC=C(F)C=C4N=C3C5=NC=CC=C5

輸送条件

Room temperature in continental US; may vary elsewhere.

保管条件
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
溶剤 & 溶解度
体外: 

DMSO : 50 mg/mL (129.74 mM; Need ultrasonic)

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 2.5947 mL 12.9735 mL 25.9471 mL
5 mM 0.5189 mL 2.5947 mL 5.1894 mL
10 mM 0.2595 mL 1.2974 mL 2.5947 mL
*Please refer to the solubility information to select the appropriate solvent.
体内:
  • 1.

    Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% saline

    Solubility: ≥ 2.5 mg/mL (6.49 mM); Clear solution

  • 2.

    Add each solvent one by one:  10% DMSO    90% (20% SBE-β-CD in saline)

    Solubility: ≥ 2.5 mg/mL (6.49 mM); Clear solution

  • 3.

    Add each solvent one by one:  10% DMSO    90% corn oil

    Solubility: ≥ 2.5 mg/mL (6.49 mM); Clear solution

*All of the co-solvents are provided by MCE.
参考文献
キナーゼ実験
[1]

A PI3K Alphascreen assay is used to measure the activity of a panel of four phosphoinositide 3-kinases: PI3Kα, PI3Kβ, PI3Kγ, and PI3Kδ. Enzyme reaction buffer is prepared using sterile water and 50 mM Tris-HCl, pH 7, 14 mM MgCl2, 2 mM sodium cholate, and 100 mM NaCl. 2 mM DTT is added fresh on the day of the experiment. The Alphascreen buffer is made using sterile water and 10 mM Tris-HCl, pH 7.5, 150 mM NaCl, 0.10% Tween 20, and 30 mM EDTA. Then 1 mM DTT is added fresh on the day of the experiment. Compound source plates used for this assay are 384-well Greiner clear polypropylene plates containing test compounds at 5 mM and diluted 1:2 over 22 concentrations. Columns 23 and 24 contained only DMSO, as these wells comprised the positive and negative controls, respectively. Source plates are replicated by transferring 0.5 μL per well into 384-well Optiplates. Each PI3K isoform is diluted in enzyme reaction buffer to 2× working stocks. PI3Kα is diluted to 1.6 nM, PI3Kβ is diluted to 0.8 nM, PI3Kγ is diluted to 15 nM, and PI3Kδ is diluted to 1.6 nM. PI(4,5)P2 is diluted to 10 μM, and ATP is diluted to 20 μM. This 2× stock is used in the assays for PI3Kα and PI3Kβ. For assay of PI3Kγ and PI3Kδ, PI(4,5)P2 is diluted to 10 μM and ATP is diluted to 8 μM to prepare a similar 2× working stock. Alphascreen reaction solutions are made using beads from the anti-GST Alphascreen kit. Two 4× working stocks of the Alphascreen reagents are made in Alphascreen reaction buffer. In one stock, biotinylated-IP4 is diluted to 40 nM and streptavadin-donor beads are diluted to 80 μg/mL. In the second stock, PIP3-binding protein is diluted to 40 nM and anti-GST-acceptor beads are diluted to 80 μg/mL. The plates are incubated at room temperature for 30 min. Still in the dark, 10 μL/well of the acceptor bead solution is added to columns 1-24 of the plates. The plates are then incubated in the dark for 1.5 h. The plates are read on an Envision multimode plate reader using a 680 nm excitation filter and a 520-620 nm emission filter[1].

MCE はこれらの方法の精度を確認していません。 こちらは参照専用です。

細胞実験
[1]

B cells are purified from human peripheral blood mononuclear cells (PBMCs) by negative selection. Approximately 3×104 purified B cells per well are seeded into a 96-well plate. Compounds (e.g., AMG319) are dissolved in DMSO at a concentration of 10 mM, and a 10-point, 3-fold serial dilution of the compound is carried out in DMSO. Then 0.5 μL of compound is added to each well in duplicates so that the final DMSO concentration is 0.25% and the highest compound concentration is 10 μM. After preincubating for 30 min, B cells are treated with 2 μg/mL of anti-human IgM antibody plus 300 ng/mL human CD40L or 5 ng/mL human IL-4 plus 200 ng/mL of CD40L as a counterscreen to evaluate the off-target effects. The plates are incubated at 37°C and 5% CO2 for 72 h, then pulsed with 0.5 μCi per well 3H thymidine for 18 h, and B cells are collected to count the incorporation of 3H thymidine[1].

MCE はこれらの方法の精度を確認していません。 こちらは参照専用です。

動物実験
[1]

Mice[1]
IgM membrane only homozygous transgenic mice (6- to 12-week-old female) are orally dosed with AMG319 or vehicle control (n=5 per group). At 15 min after treatment, mice are tail iv injected with 50 μg of Endotoxin-free FITC-labeled μ chain specific anti-IgM or PBS only control. Blood and spleen tissue are collected after 30 min of stimulation for drug concentration and B cell pAKT analysis via flow cytometry. Briefly, blood and dispersed splenocytes are fixed with BD Phosflow lyse/fix buffer, pelleted, and permeabilized with cold 90% MeOH. Cells are then stained with pAKT and Alexa-647 secondary and B220-Pacific Blue for FACS analysis. Stimulated B220+/anti-IgM FITC+ B cells are analyzed for pAKT levels with B220+/FITC-B cells from anti-IgM untreated mice serving as a control. Mice are maintained and experiments are performed.
Rats[1]
Female Lewis rats (N=8/dose group) are dosed po with AMG319 or vehicle (2% HPMC, 1% Pluronic F68, 10% Captisol, pH 2.0) once a day for 10 days at various doses. Two hours after the first dosing, 200 μL of PBS containing 60 μg of KLH is administered to each rat intravenously. Ten days after the KLH priming, rats are euthanized and blood is taken by cardiac puncture for the measurement of KLH specific IgG and IgM by ELISA.

MCE はこれらの方法の精度を確認していません。 こちらは参照専用です。

参考文献
  • No file chosen (Maximum size is: 1024 Kb)
  • If you have published this work, please enter the PubMed ID.
  • Your name will appear on the site.
  • モル濃度カルキュレーター

  • 希釈カルキュレーター

The molarity calculator equation

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass   Concentration   Volume   Molecular Weight *
= × ×

The dilution calculator equation

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
× = ×
C1   V1   C2   V2

Keywords:

AMG319AMG 319AMG-319PI3KPhosphoinositide 3-kinaseInhibitorinhibitorinhibit

最近チェックした製品:

オンラインお問い合わせ

Your information is safe with us. * Required Fields.

製品名

 

タイトル

お名前 *

 

PC 用メールアドレス *

電話番号 *

 

勤務先/学校名 *

Department *

 

カスタマ需要量 *

国会或いは地域 *

     

必ず会社名を記載ください。個人への返信は行いません。

メッセージ

バルクお問い合わせ

Inquiry Information

製品名:
AMG319
製品番号:
HY-12948
数量:
MCE 日本正規代理店: