CGI-1746 [910232-84-7]

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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

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
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 2 years
-20°C 1 year
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
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 1.7251 mL 8.6253 mL 17.2506 mL
5 mM 0.3450 mL 1.7251 mL 3.4501 mL
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.
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.

  • Calculadora de molaridad

  • Calculadora de dilución

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

Mass
=
Concentration
×
Volume
×
Molecular Weight *

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

This equation is commonly abbreviated as: C1V1 = C2V2

Concentration (start)

C1

×
Volume (start)

V1

=
Concentration (final)

C2

×
Volume (final)

V2

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:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

  • Protocol 1

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

    Solubility: ≥ 2.5 mg/mL (4.31 mM); Clear solution

    This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

    Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
  • Protocol 2

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

    Solubility: 2.5 mg/mL (4.31 mM); Suspended solution; Need ultrasonic

    This protocol yields a suspended solution of 2.5 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

    Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

g

Dosing volume
(per animal)

μL

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
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%

Referencias
  • [1]. Di Paolo, Julie A. et al. Specific Btk inhibition suppresses B cell- and myeloid cell-mediated arthritis. Nature Chemical Biology (2011), 7(1), 41-50  [Content Brief]

    [2]. Kokabee L, et al. Bruton's tyrosine kinase is a potential therapeutic target in prostate cancer. Cancer Biol Ther. 2015;16(11):1604-15  [Content Brief]

Ensayo celular
[2]

5×103 DU145 cells or 104 LNCaP cells per well, grown on 96 well plates for 24h, are treated with 1 to 30 µM BTK inhibitors. Cells are fixed after 72h with 2.5% formaldehyde, and stained with Hoechst 33342. Control cells are treated with DMSO. Cell images are acquired using an IN Cell Analyzer 2200 high content imaging system, with a 20X objective. At least 9 fields are imaged per single well of each experiment. Cell numbers are determined and statistics performed using IN Cell Investigator 3.4 high content image analysis software. Each experiment is replicated 3 times, and data are presented as mean±SD. Results are considered significant if p < 0.05.

MCE no ha confirmado la precisión de estos métodos independientemente. Son solo para referencia.

Referencias
  • [1]. Di Paolo, Julie A. et al. Specific Btk inhibition suppresses B cell- and myeloid cell-mediated arthritis. Nature Chemical Biology (2011), 7(1), 41-50  [Content Brief]

    [2]. Kokabee L, et al. Bruton's tyrosine kinase is a potential therapeutic target in prostate cancer. Cancer Biol Ther. 2015;16(11):1604-15  [Content Brief]

  • [1]. Di Paolo, Julie A. et al. Specific Btk inhibition suppresses B cell- and myeloid cell-mediated arthritis. Nature Chemical Biology (2011), 7(1), 41-50

    [2]. Kokabee L, et al. Bruton's tyrosine kinase is a potential therapeutic target in prostate cancer. Cancer Biol Ther. 2015;16(11):1604-15

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
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CGI-1746 Related Classifications

  • Protein Tyrosine Kinase/RTK Autophagy
  • Btk Autophagy
Help & FAQs

Keywords:

CGI-1746910232-84-7CGI1746CGI 1746BtkAutophagyBruton tyrosine kinaseInhibitorinhibitorinhibit

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HY-15346-5mg
 5mg