CGI-1746 [910232-84-7]
Referencia HY-11999-10mg
embalaje : 10mg
Marca : MedChemExpress
CGI-1746 is a potent and highly selective inhibitor of the?Btk?with?IC50?of 1.9 nM.
Para uso exclusivo en investigación. No vendemos a pacientes.
CGI-1746 Estructura química
No. CAS : 910232-84-7
This product is a controlled substance and not for sale in your territory.
Based on 5 publication(s) in Google Scholar
Descripciòn |
CGI-1746 is a potent and highly selective inhibitor of the?Btk?with?IC50?of 1.9 nM. |
||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
IC50 & Target |
IC50: 1.9 nM (Btk) |
||||||||||||
In Vitro |
CGI1746 is specific for Btk, with appr 1,000-fold selectivity over Tec and Src family kinases. In an ATP-free competition binding assay, the dissociation constant for Btk is 1.5 nM. CGI1746 inhibits Btk activity in a new binding mode that stabilizes an inactive nonphosphorylated enzyme conformation. CGI1746 inhibits both auto- and transphosphorylation steps necessary for enzyme activation. CGI1746 completely inhibits anti-IgM-induced murine and human B cell proliferation, with IC50s of 134 nM and 42 nM, respectively, but has no effect on anti-CD3- and anti-CD28-induced T cell proliferation. CGI1746 potently inhibits the proliferation of CD27+IgG+ B cells isolated from the tonsils of four human donors with an average IC50 of 112 nM. In macrophages, CGI1746 abolishes FcγRIII-induced TNFα, IL-1β and IL-6 production. CGI1746 potently inhibits TNFα, IL-1β and, to a lesser extent, IL-6 (three- to eight-fold higher IC50) production in human monocytes stimulated with immobilized or soluble immune complexes[1].?CGI-1746 does not kill cells as well as the irreversible BTK inhibitors at the same drug concentration. CGI-1746 significantly reduces phosphorylation of both the BTK-A and BTK-C proteins, indicating the auto-phosphorylation of the BTK-C isoform is inhibited in a manner similar to BTK-A. CGI-1746 does not kill LNCaP or DU145 prostate cancer cells at the same concentrations as Ibrutinib or AVL-292, but it demonstrates similar inhibition of BTK phosphorylation at tyrosine 233 in the SH3 domain[2]. MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. |
||||||||||||
In Vivo |
CGI1746 abrogates B cell-dependent arthritis. CGI1746 treatment (100 mg/kg, s.c, twice-daily dosing) results in significant inhibition (97%) of overall clinical arthritis scores. CGI1746 treatment substantially reduces TNFα, IL-1β and IL-6, as well as MCP1 and MIP-1α on both the mRNA and protein level in the passive anti-collagen II antibody-induced arthritis (CAIA) model. CGI1746 shows comparable efficacy to TNFα blockade and significantly reduces clinical scores, as well as joint inflammation, in mice or rats with established arthritis[1]. MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. |
||||||||||||
Peso molecular |
579.69 |
||||||||||||
Fòrmula |
C34H37N5O4 |
||||||||||||
No. CAS |
910232-84-7 |
||||||||||||
Appearance |
Solid |
||||||||||||
Color |
White to light yellow |
||||||||||||
SMILES |
O=C(C1=CC=C(C=C1)C(C)(C)C)NC2=CC=CC(C(N=C3NC4=CC=C(C=C4)C(N5CCOCC5)=O)=CN(C3=O)C)=C2C |
||||||||||||
Envío | Room temperature in continental US; may vary elsewhere. |
||||||||||||
Almacenamiento |
|
||||||||||||
Solvente y solubilidad |
In Vitro:
DMSO : ≥ 50 mg/mL (86.25 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO) *"≥" means soluble, but saturation unknown. Preparing
Stock Solutions
View the Complete Stock Solution Preparation Table
*
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol) Concentration (start) × Volume (start) = Concentration (final) × Volume (final) This equation is commonly abbreviated as: C1V1 = C2V2 In Vivo:
Select the appropriate dissolution method based on your experimental animal and administration route.
For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
Dosage mg/kgAnimal weight Dosing volume Number of animals Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
%
DMSO
+
%
+
%
Tween-80
+
%
Saline
The co-solvents required include: DMSO,
. All of co-solvents are available by MedChemExpress (MCE).
, Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Calculation results:
Working solution concentration:
mg/mL
Method for preparing stock solution:
mg
drug dissolved in
μL
DMSO (Stock solution concentration: mg/mL).
The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
Method for preparing in vivo working solution for animal experiments: Take
μL DMSO stock solution, add
μL .
μL , mix evenly, next add
μL Tween 80, mix evenly, then add
μL Saline.
If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
|
||||||||||||
Pureza y Documentación |
Purity: 99.39%
SDS (392 KB)
COA (245 KB) HNMR (158 KB) RP-HPLC (153 KB) LCMS (374 KB) Instrucciones de manejo (2659 KB) |
||||||||||||
Referencias |
|
Complete Stock Solution Preparation Table
*
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
---|
DMSO | 1 mM | 1.7251 mL | 8.6253 mL | 17.2506 mL | 43.1265 mL |
5 mM | 0.3450 mL | 1.7251 mL | 3.4501 mL | 8.6253 mL | |
10 mM | 0.1725 mL | 0.8625 mL | 1.7251 mL | 4.3126 mL | |
15 mM | 0.1150 mL | 0.5750 mL | 1.1500 mL | 2.8751 mL | |
20 mM | 0.0863 mL | 0.4313 mL | 0.8625 mL | 2.1563 mL | |
25 mM | 0.0690 mL | 0.3450 mL | 0.6900 mL | 1.7251 mL | |
30 mM | 0.0575 mL | 0.2875 mL | 0.5750 mL | 1.4375 mL | |
40 mM | 0.0431 mL | 0.2156 mL | 0.4313 mL | 1.0782 mL | |
50 mM | 0.0345 mL | 0.1725 mL | 0.3450 mL | 0.8625 mL | |
60 mM | 0.0288 mL | 0.1438 mL | 0.2875 mL | 0.7188 mL | |
80 mM | 0.0216 mL | 0.1078 mL | 0.2156 mL | 0.5391 mL |
CGI-1746 Related Classifications
- Protein Tyrosine Kinase/RTK Autophagy
- Btk Autophagy