| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
Rho/MRTF pathway
CCG-222740 targets the Rho/myocardin-related transcription factor (MRTF) pathway. It is a selective MRTF pathway inhibitor. The Rho/MRTF pathway is a critical signaling cascade that regulates the transcription of genes involved in actin cytoskeleton dynamics, cell migration, and fibrosis. By inhibiting this pathway, CCG-222740 prevents the nuclear translocation of MRTF and its subsequent coactivation of serum response factor (SRF), thereby reducing the expression of pro-fibrotic and pro-metastatic genes. |
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| ln Vitro |
CCG-222740 causes a decrease in cyclin D1 and an increase in the protein p27. Using the MTT assay, CCG-222740 treatment reduced CAFs' cell viability with an IC50 of about 10 μM. One of the primary sources of matrix proteins, including multiple isoforms of collagen, in pancreatic cancer is CAFs. In CAFsIn cancer cells, the Rho/MRTF pathway inhibitor CCG-222740 reduces the amounts of collagens I, 2a, and IV as well as α-SMA. Treatment with CCG-222740 causes MRTF to be excluded from the nucleus.[1] |
| ln Vivo |
CCG-222740 dramatically lowers the levels of α-SMA in the pancreas of KC mice stimulated with caerulein.[1] |
| Enzyme Assay |
The activity of CCG-222740 as an MRTF pathway inhibitor is typically assessed using SRF reporter gene assays, where its ability to inhibit SRF-mediated transcription is measured. These assays involve transfecting cells with a luciferase reporter construct driven by SRF response elements. The compound's effect on the expression of MRTF/SRF target genes, such as α-SMA, can be quantified by qRT-PCR or Western blot analysis.
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| Cell Assay |
The culture medium used for murine cancer-associated fibroblasts (CAFs) contains 10% fetal bovine serum (FBS). After treating CAFs with various concentrations of CCG-222740 (740) for 72 hours, the levels of p27 and Cyclin D1 are assessed using western blotting.
In vitro cellular assays for CCG-222740 involve treating various cell types, such as stellate cells or cancer-associated fibroblasts (CAFs), with the compound and assessing cell viability, protein expression, and gene expression. Cell viability is commonly measured using MTT or CellTiter-Glo assays. The compound's ability to inhibit α-SMA expression is assessed by Western blot. Its effect on SRF reporter gene activity is measured using luciferase assays. |
| Animal Protocol |
Nine-week old KC mice
100 mg/kg Oral gavage In vivo animal model protocols for CCG-222740 involve its oral administration to animal models of fibrosis and cancer metastasis. In skin fibrosis models, the compound's ability to reduce collagen deposition and α-SMA expression is assessed. In melanoma metastasis models, its ability to block metastatic spread is evaluated. The compound's effects on disease progression and pharmacodynamic markers of pathway inhibition are typically measured. |
| ADME/Pharmacokinetics |
CCG-222740 is an orally active compound. Specific pharmacokinetic data is not extensively detailed in the available literature, but its oral bioavailability has been demonstrated in preclinical studies. The compound is soluble in DMSO and is typically stored as a solid at -20°C for long-term stability.
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| Toxicity/Toxicokinetics |
Specific toxicological data for CCG-222740 is not extensively detailed in the available literature. As a research compound, it is intended for research use only and not for human consumption. Standard safety assessments would be required for clinical development.
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| References |
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| Additional Infomation |
CCG-222740 (CAS# 1922098-69-8) is a research compound used to study the Rho/MRTF/SRF pathway. It is an orally active and selective inhibitor of the Rho/MRTF pathway. The compound is a potent inhibitor of alpha-smooth muscle actin protein expression and effectively reduces fibrosis in skin and blocks melanoma metastasis. It is not approved for clinical use and is intended for research purposes only.
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| Molecular Formula |
C23H19CLF2N2O3
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|---|---|
| Molecular Weight |
444.858371973038
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| Exact Mass |
444.105
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| Elemental Analysis |
C, 62.10; H, 4.31; Cl, 7.97; F, 8.54; N, 6.30; O, 10.79
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| CAS # |
1922098-69-8
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| Related CAS # |
1922098-69-8
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| PubChem CID |
121317937
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
4.4
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
31
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| Complexity |
657
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1C(CN(CC1(F)F)C(=O)C2=CC=CC(=C2)C3=CC=CO3)C(=O)NC4=CC=C(C=C4)Cl
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| InChi Key |
PMTPYUTZAJWGPE-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H19ClF2N2O3/c24-18-6-8-19(9-7-18)27-21(29)17-12-23(25,26)14-28(13-17)22(30)16-4-1-3-15(11-16)20-5-2-10-31-20/h1-11,17H,12-14H2,(H,27,29)
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| Chemical Name |
N-(4-chlorophenyl)-5,5-difluoro-1-[3-(furan-2-yl)benzoyl]piperidine-3-carboxamide
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| Synonyms |
CCG222740; CCG 222740; CCG-222740
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO: ~125 mg/mL (~281 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.25 mg/mL (5.06 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 22.5 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. Solubility in Formulation 2: 2.25 mg/mL (5.06 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 ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 22.5 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. View More
Solubility in Formulation 3: ≥ 2.25 mg/mL (5.06 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2479 mL | 11.2395 mL | 22.4790 mL | |
| 5 mM | 0.4496 mL | 2.2479 mL | 4.4958 mL | |
| 10 mM | 0.2248 mL | 1.1239 mL | 2.2479 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.
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.
(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.
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