CCG-203971

Alias: CCG203971; CCG 203971; CCG-203971

Cat No.:V3118 Purity: ≥98%

COA Product Data Instructions for use SDS

CCG-203971 is a novel, 2nd generation small-molecule inhibitor of the Rho/MRTF/SRF [RhoA/myocardin-related transcription factor A (MRTF-A)] pathway with an IC50 value of 0.64 μM for SRE.

CCG-203971 Chemical Structure CAS No.: 1443437-74-8
Product category: Ras

This product is for research use only, not for human use. We do not sell to patients.

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Citations by Top Journals: Nature, Cell, Science, etc.

Top Publications Citing lnvivochem Products

Nature 2021, 597(7874):119-125.

Cell 2020,183:1202-1218.e25.

Science Adv 2022: 8, eabm9427.

Nature 597, 119–125 (2021)

Cell Stem Cell 2020,26(6):845-861.e12.

Science Trans Med 2023,15(701):eadd7872.

STTT 2023,8(1):91.

Cell Reports 2023,42(4):112313

Science Trans Med 2023, 15: eadd7872.

Cancer Cell 2021,39(4):529-547.e7.

Cancer Discov 2022,12(4):1106-1127.

Immunity 2023,56(3):620-634.e11.

J Am Chem Soc 2022,144:21831-21836.

Cell 2020,183:1202-1218.e25.

Science Adv 2022:8,eabm9427.

Nature 2021,597(7874):119-125.

Cell 2020,183:1202-1218.e25.

PNAS Nexus 2022,1(3):pgac063.

ACS Nano 2023,17(10):9110-9125.

Biomaterial 2023 Sep16:302:122333.

Purity & Quality Control Documentation

Current batch：

Purity: ≥98%

COA

MSDS

Instructions

Product Description
Bioactivity & Protocols
Physicochemical Properties
Solubility Data
Calculators
Biological Data

Product Description

CCG-203971 is a novel, 2nd generation small-molecule inhibitor of the Rho/MRTF/SRF [RhoA/myocardin-related transcription factor A (MRTF-A)] pathway with an IC50 value of 0.64 μM for SRE. CCG-203971 suppresses the expression of collagen 1 (COL1A2), α-smooth muscle actin (α-SMA), and connective tissue growth factor (CTGF) in SSc fibroblasts as well as fibroblasts stimulated by transforming growth factor β (TGFβ) and lysophosphatidic acid (LPA). At a concentration of 25 μM, CCG-203971 significantly suppresses MKL1 expression induced by TGF-β.

Biological Activity I Assay Protocols (From Reference)

Targets

Rho; SRE.L ( IC50 = 0.64 μM )

ln Vitro

In vitro activity: CCG-203971 suppresses the expression of collagen 1 (COL1A2), α-smooth muscle actin (α-SMA), and connective tissue growth factor (CTGF) in SSc fibroblasts as well as fibroblasts stimulated by transforming growth factor β (TGFβ) and lysophosphatidic acid (LPA)[2].

ln Vivo

CCG-203971 shows encouraging anti-fibrotic activity in a number of animal disease models, including intestinal, pulmonary, and dermal fibrosis, both in vitro and in vivo. CCG-203971 has a half-life of only 1.6 minutes in mouse liver microsomes (MLM), which suggests that it is highly susceptible to oxidative metabolism[1]. Moreover, bleomycin-induced skin thickening and collagen deposition are prevented by CCG-203971 in vivo treatment[2].

Cell Assay

Plated into a 96-well plate, human dermal fibroblasts (2.0 × 10⁴) are cultured in DMEM containing 10% FBS for an entire night. After removing the media, they are replaced with DMEM that contains 0.1% DMSO control or 30 μM CCG-203971 along with 2% FBS. WST-1 dye is added to each well after 72 hours, and the absorbance at 490 nm is measured after 60 minutes.

Animal Protocol

Mice: In C57BL/6 mice (female, 8 weeks old), a local intracutaneous injection of 100 μL of Bleomycin (1 mg/mL) in phosphate-buffered saline (PBS) is administered daily for two weeks in a predetermined area (~1 cm2) on the upper back to induce skin fibrosis. A control is a 100 μL intracutaneous injection of PBS. A total of 21 mice are used, divided into three groups. Two groups are given bleomycin challenges while the first group is given PBS injections. During the first two weeks of the Bleomycin challenge, 100 mg/kg of CCG-203971 administered intraperitoneally twice daily in 50 μL of DMSO is started. The vehicle control system is DMSO. The animal groups are as follows: (1) Bleomycin/DMSO; (2) PBS/DMSO; and (3) Bleomycin/CCG-203971. Following therapy, cervical dislocation is used to humanely kill the animals, and tissue is gathered.

References

[1]. Bioorg Med Chem Lett . 2017 Apr 15;27(8):1744-1749.

[2]. J Pharmacol Exp Ther . 2014 Jun;349(3):480-6.

These protocols are for reference only. InvivoChem does not independently validate these methods.

Physicochemical Properties

Molecular Formula

C23H21CLN2O3

Molecular Weight

408.88

Exact Mass

408.124

Elemental Analysis

C, 67.56; H, 5.18; Cl, 8.67; N, 6.85; O, 11.74

CAS #

1443437-74-8

Related CAS #

1443437-74-8

PubChem CID

71681561

Appearance

White to off-white solid powder

Density

1.3±0.1 g/cm3

Boiling Point

656.0±55.0 °C at 760 mmHg

Flash Point

350.5±31.5 °C

Vapour Pressure

0.0±2.0 mmHg at 25°C

Index of Refraction

1.633

LogP

3.76

Hydrogen Bond Donor Count

Hydrogen Bond Acceptor Count

Rotatable Bond Count

Heavy Atom Count

Complexity

579

Defined Atom Stereocenter Count

SMILES

ClC1C([H])=C([H])C(=C([H])C=1[H])N([H])C(C1([H])C([H])([H])N(C(C2=C([H])C([H])=C([H])C(C3=C([H])C([H])=C([H])O3)=C2[H])=O)C([H])([H])C([H])([H])C1([H])[H])=O

InChi Key

HERLZBNILRVHQN-UHFFFAOYSA-N

InChi Code

InChI=1S/C23H21ClN2O3/c24-19-8-10-20(11-9-19)25-22(27)18-6-2-12-26(15-18)23(28)17-5-1-4-16(14-17)21-7-3-13-29-21/h1,3-5,7-11,13-14,18H,2,6,12,15H2,(H,25,27)

Chemical Name

N-(4-chlorophenyl)-1-[3-(furan-2-yl)benzoyl]piperidine-3-carboxamide

Synonyms

CCG203971; CCG 203971; CCG-203971

HS Tariff Code

2934.99.9001

Storage

Powder -20°C 3 years

4°C 2 years

In solvent -80°C 6 months

-20°C 1 month

Shipping Condition

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility Data

Solubility (In Vitro)

DMSO: 81~250 mg/mL (198.1~611.4 mM)

Water: < 1mg/mL

Ethanol: ~4 mg/mL (~9.8 mM)

Solubility (In Vivo)

Solubility in Formulation 1: 2.5 mg/mL (6.11 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

Solubility in Formulation 2: ≥ 2.08 mg/mL (5.09 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.08 mg/mL (5.09 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

Solubility in Formulation 4: 10% DMSO: 40% PEG300: 5% Tween-80: 45% saline: ≥ 2.5 mg/mL

(Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.4457 mL	12.2285 mL	24.4571 mL
	5 mM	0.4891 mL	2.4457 mL	4.8914 mL
	10 mM	0.2446 mL	1.2229 mL	2.4457 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

Calculator

Mass

Concentration

Volume

Molecular Weight*

Molarity Calculator allows you to calculate the mass, volume, and/or concentration required for a solution, as detailed below:

Calculate the Mass of a compound required to prepare a solution of known volume and concentration
Calculate the Volume of solution required to dissolve a compound of known mass to a desired concentration
Calculate the Concentration of a solution resulting from a known mass of compound in a specific volume

See Example

An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?

Enter 350.26 in the Molecular Weight (MW) box
Enter 10 in the Concentration box and choose the correct unit (mM)
Enter 5 in the Volume box and choose the correct unit (mL)
Click the “Calculate” button
The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

Concentration (Start)

Volume (Start)

Concentration (End)

Volume (End)

Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:

Enter 10 into the Concentration (Start) box and choose the correct unit (mM)
Enter 25 into the Concentration (End) box and select the correct unit (mM)
Enter 25 into the Volume (End) box and choose the correct unit (mL)
Click the “Calculate” button
The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box

Molecular formula

Total molecular weight

g/mol

Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4 c12h18n3o4
Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter the chemical/molecular formula and click the “Calculate’ button.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (or molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

Volume (to add to vial)

Mass (in vial)

Desired Reconstitution Concentration

Reconstitution Calculator allows you to calculate the volume of solvent required to reconstitute your vial.

Enter the mass of the reagent and the desired reconstitution concentration as well as the correct units
Click the “Calculate” button
The answer appears in the Volume (to add to vial) box

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)

Dosage mg/kg

Average weight of animals g

Dosing volume per animal μL

Number of animals

Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)

% DMSO

% Tween 80

% ddH₂O

Calculation results

Working concentration： mg/mL；

Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O，mix and clarify.

Note： (1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.

Biological Data

CCG-203971

LPA activates fibrotic gene expression in 3T3 fibroblasts in a Rho/MRTF-dependent manner. NIH-3T3 cells were treated with the indicated concentration of CCG-203971 or DMSO for 23 hours. One hour prior to RNA isolation, cells were stimulated with 10μM LPA.J Pharmacol Exp Ther.2014 Jun;349(3):480-6.

SSc-patient dermal fibroblasts show increased expression of fibrosis markers/MRTF target genes, which are inhibited by CCG-203971.J Pharmacol Exp Ther.2014 Jun;349(3):480-6.
Scleroderma dermal fibroblasts proliferate faster than normal cells, and this is inhibited by CCG-203971.J Pharmacol Exp Ther.2014 Jun;349(3):480-6.
CCG-203971 modulates myofibroblast transition of dermal fibroblasts.J Pharmacol Exp Ther.2014 Jun;349(3):480-6.
CCG-203971 prevents bleomycin-induced fibrosis in vivo.J Pharmacol Exp Ther.2014 Jun;349(3):480-6.

CCG-203971

8f (CCG-203971)inhibits bleomycin-induced skin fibrosis in mice. Three groups of mice (n=8) were treated for 14 days with one of the following daily protocols: Control: intracutaneous injections of PBS; Bleo: intracutaneous injections of bleomycin with concurrent oral gavage of vehicle; or Bleo + 8f: intracutaneous injections of bleomycin with concurrent oral gavage of 50 mg/kg8f.Bioorg Med Chem Lett.2017 Apr 15;27(8):1744-1749.