1443437-74-8
1443437-74-8 structure
- Name: CCG 203971
- Chemical Name: N-(4-chlorophenyl)-1-(3-(furan-2-yl)benzoyl)piperidine-3-carboxamide
- CAS Number: 1443437-74-8
- Molecular Formula: C23H21ClN2O3
- Molecular Weight: 408.877
- Catalog: Signaling Pathways GPCR/G Protein Ras
- Create Date: 2018-02-16 12:22:10
- Modify Date: 2024-01-14 08:44:51
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CCG-203971 is a second-generation RhoA/myocardin-related transcription factor A (MRTF-A) inhibitor. CCG-203971 potently targets RhoA/C-activated serum response element (SRE)-luciferase (IC50=6.2 μM).
| Name | N-(4-chlorophenyl)-1-(3-(furan-2-yl)benzoyl)piperidine-3-carboxamide |
|---|---|
| Synonyms |
N-(4-Chlorophenyl)-1-[3-(2-furyl)benzoyl]-3-piperidinecarboxamide
3-Piperidinecarboxamide, N-(4-chlorophenyl)-1-[3-(2-furanyl)benzoyl]- CCG-203971 |
| Description | CCG-203971 is a second-generation RhoA/myocardin-related transcription factor A (MRTF-A) inhibitor. CCG-203971 potently targets RhoA/C-activated serum response element (SRE)-luciferase (IC50=6.2 μM). |
|---|---|
| Related Catalog | |
| Target |
RhoA/MRTF-A[1] |
| In Vitro | CCG-203971, a second-generation Ras homolog gene family, member A (RhoA)/myocardin-related transcription factor A (MRTF-A)/serum response factor (SRF) pathway inhibitor, represses both matrix-stiffness and transforming growth factor beta–mediated fibrogenesis as determined by protein and gene expression in a dose-dependent manner. CCG-203971 significantly represses TGF-β- induced MKL1 expression at 25 μM concentration[1]. Human dermal fibroblasts are plated onto 96-well plates and allowed to grow for 3 days in the presence of 30 μM CCG-203971 or DMSO vehicle. Viable cell density is assessed through enzymatic reduction of the water-soluble tetrazolium dye WST-1. Scleroderma dermal fibroblasts proliferate faster than normal cells, and this is inhibited by CCG-203971[2]. |
| In Vivo | CCG-203971 is tested in a Bleomycin skin injury model. Bleomycin is administered in 50 μL of DMSO intraperitoneally. Preliminary studies show that Bleomycin administered in this manner is well tolerated at 100 mg/kg twice a day. Intradermal Bleomycin for 2 weeks along with the DMSO control (50 μL i.p.) results in marked dermal thickening (P<0.0001) compared with the PBS+DMSO group, which does not receive Bleomycin. CCG-203971 treatment strongly and significantly (P<0.001) suppresses the Bleomycin-induced skin thickening in this model. Skin collagen amounts, assessed by measurement of hydroxyproline content, show similar results. Bleomycin injections promote collagen deposition (P<0.01) and CCG-203971 is able to block this effect (P<0.05)[2]. |
| Cell Assay | Human dermal fibroblasts (2.0×104) are plated into a 96-well plate and grown overnight in DMEM containing 10% FBS. Media are removed and replaced with DMEM containing 2% FBS and 30 μM CCG-203971 or 0.1% DMSO control. After 72 hours WST-1 dye is added to each well, and after 60 minutes absorbance at 490 nm is read using a Wallac Victor2 plate reader[2]. |
| Animal Admin | Mice[2] Skin fibrosis is induced in C57BL/6 mice (female, 8 weeks old) by local intracutaneous injection of 100 μL of Bleomycin (1 mg/mL) in phosphate-buffered saline (PBS), every day for 2 weeks in a defined area (~1 cm2) on the upper back. Intracutaneous injection of 100 μL of PBS is used as a control. Three groups of mice with a total of 21 mice are used. One group receives injections of PBS and the other two are challenged with Bleomycin. Twice-a-day intraperitoneal administration of CCG-203971 (100 mg/kg in 50 μL of DMSO) is initiated together with the first challenge of Bleomycin and continues for 2 weeks. DMSO is used as the vehicle control. The three groups of animals are: (1) PBS/DMSO; (2) Bleomycin/DMSO; and (3) Bleomycin/CCG-203971. After treatment, animals are humanely killed by cervical dislocation, and tissue is collected[2]. |
| References |
| Density | 1.3±0.1 g/cm3 |
|---|---|
| Boiling Point | 656.0±55.0 °C at 760 mmHg |
| Molecular Formula | C23H21ClN2O3 |
| Molecular Weight | 408.877 |
| Flash Point | 350.5±31.5 °C |
| Exact Mass | 408.124084 |
| PSA | 62.55000 |
| LogP | 3.76 |
| Vapour Pressure | 0.0±2.0 mmHg at 25°C |
| Index of Refraction | 1.633 |
| Storage condition | -20℃ |
| Symbol |
GHS07 |
|---|---|
| Signal Word | Warning |
| Hazard Statements | H302 |
| Precautionary Statements | P301 + P312 + P330 |
| RIDADR | NONH for all modes of transport |