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CGI-1746

カタログ番号GC13365

強力で選択的なBTK阻害剤

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CGI-1746 化学構造

Cas No.: 910232-84-7

サイズ 価格 在庫数 個数
10mM (in 1mL DMSO)
$312.00
在庫あり
10mg
$140.00
在庫あり
50mg
$486.00
在庫あり
100mg
$846.00
在庫あり

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Sample solution is provided at 25 µL, 10mM.

Product Documents

Quality Control & SDS

View current batch:

Protocol

Cell experiment [1]:

Cell lines

Human B cells

Preparation method

The solubility of this compound in DMSO is > 29 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months.

Reacting condition

0.003 ~ 10 μM

Applications

In human B cells, CGI-1746 potently inhibited anti-IgM-induced phosphorylation of Btk Tyr223, Btk Tyr551 and PLCγ2 Tyr1217, with an average IC50 value of 2.9 nM. In addition, CGI-1746 lowered the basal phosphorylation levels of Btk Tyr551 and Tyr223, but not the basal phosphorylation of PLCγ2 Tyr1217.

Animal experiment [1]:

Animal models

Collagen-induced arthritis (CIA) mouse model

Dosage form

100 mg/kg; s.c.; b.i.d., from day 12 to day 26

Applications

CGI-1746 significantly inhibited overall clinical arthritis scores (97% inhibition). Moreover, CGI-1746 substantially reduced anti-collagen II (CII) titers.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

[1]. Di Paolo JA, Huang T, Balazs M, et al. Specific Btk inhibition suppresses B cell- and myeloid cell-mediated arthritis. Nat Chem Biol, 2011, 7(1): 41-50.

Background

CGI-1746は、Bruton's tyrosine kinase(BTK)の選択的かつ強力な阻害剤であり、IC50値は1.9 nMです[1][2]。BTKはTecチロシンキナーゼファミリーのメンバーであり、B細胞の分化、増殖および発達に重要な役割を果たしています。それはB細胞性悪性腫瘍、関節リウマチ(RA)、多発性硬化症(MS)およびループスなどの免疫学的障害の治療にとって魅力的なターゲットです[3]。CGI-1746は自己および他己リン酸化両方を強力に阻害します。未リン酸化されたBTKに結合し、非活性酵素状態で安定させます。細胞アッセイでは、CGI-1746がBCR介在性B細胞増殖をブロックし、マクロファージ中のIL-6、IL-1βおよびTNF産生を抑制することが示されています[1]。
実験的マウスモデルでは、CGI-1746が強力な抗関節炎活性を示します[1]。B10.RIIIマウスモデルでは、CGI1746は臨床的関節炎スコアの有意な抑制(97%)をもたらし、デキサメタゾン治療(56%抑制)よりも優れていました[2]。
参考文献:
[1]. Akinleye A, Chen Y, Mukhi N, et al. Ibrutinib and novel BTK inhibitors in clinical development. J Hematol Oncol, 2013, 6: 59.
[2]. Di Paolo JA, Huang T, Balazs M, et al. Specific Btk inhibition suppresses B cell- and myeloid cell-mediated arthritis. Nat Chem Biol, 2011, 7(1): 41-50.
[3]. Young WB、Barbosa J、Blomgren P、et al。強力で選択的なBruton's tyrosine kinase阻害剤:GDC-0834の発見。Bioorg Med Chem Lett、2015年25(6):1333-1337。

Chemical Properties

Cas No. 910232-84-7 SDF
Chemical Name 4-tert-butyl-N-[2-methyl-3-[4-methyl-6-[4-(morpholine-4-carbonyl)anilino]-5-oxopyrazin-2-yl]phenyl]benzamide
Canonical SMILES CC1=C(C=CC=C1NC(=O)C2=CC=C(C=C2)C(C)(C)C)C3=CN(C(=O)C(=N3)NC4=CC=C(C=C4)C(=O)N5CCOCC5)C
Formula C34H37N5O4 M.Wt 579.71
溶解度 ≥ 29 mg/mL in DMSO, ≥ 6.72 mg/mL in EtOH with ultrasonic and warming Storage Store at -20°C
General tips Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month.
To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
Shipping Condition Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.

Complete Stock Solution Preparation Table

Prepare stock solution
1 mg 5 mg 10 mg
1 mM 1.725 mL 8.625 mL 17.25 mL
5 mM 0.345 mL 1.725 mL 3.45 mL
10 mM 0.1725 mL 0.8625 mL 1.725 mL
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計算

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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.

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