CCG-203971, a novel inhibitor of Rho-mediated gene transcription. CCG-203971 is efficacious in multiple animal models of acute fibrosis, including scleroderma, when given intraperitoneally[3]. CCG-203971 inhibits PC-3 cell migration with an IC50 of 4.2 μM[4]. CCG-203971 has a significant reduction of melanoma metastasis and bleomycin- induced fibrosis[5]. CCG-203971, is also a novel small-molecule inhibitor of MRTF/SRF-regulated transcription, inhibits expression of connective tissue growth factor (CTGF), α-smooth muscle actin (α-SMA), and collagen 1 (COL1A2) in both SSc fibroblasts and in lysophosphatidic acid (LPA)-and transforming growth factor β (TGFβ)-stimulated fibroblasts. In vivo treatment with CCG-203971 also prevented bleomycin-induced skin thickening and collagen deposition[6].
CCG-203971 细胞实验
Cell Line
Concentration
Treated Time
Description
References
CCL-210 fibroblasts
30 μmol/L
8 hours
To assess the effect of CCG-203971 on Fas-mediated apoptosis. Results showed that CCG-203971 significantly enhanced Fas-mediated apoptosis.
Am J Pathol. 2015 Apr;185(4):969-86.
IMR-90 fibroblasts
30 μmol/L
16 hours
To assess the effect of CCG-203971 on Fas-mediated apoptosis. Results showed that CCG-203971 significantly enhanced Fas-mediated apoptosis.
Am J Pathol. 2015 Apr;185(4):969-86.
CCL-210 fibroblasts
30 μmol/L
24 hours
To assess the effect of CCG-203971 on TGF-β1-induced fibronectin expression. Results showed that 30 μmol/L CCG-203971 completely abrogated TGF-β1-induced fibronectin deposition.
Am J Pathol. 2015 Apr;185(4):969-86.
CCL-210 fibroblasts
30 μmol/L
24 hours
To assess the effect of CCG-203971 on TGF-β1-induced α-SMA expression. Results showed that 30 μmol/L CCG-203971 significantly suppressed TGF-β1-mediated α-SMA expression.
Am J Pathol. 2015 Apr;185(4):969-86.
IMR-90 fibroblasts
30 μmol/L
24 hours
To assess the effect of CCG-203971 on MRTF-A nuclear localization. Results showed that CCG-203971 significantly reduced MRTF-A nuclear localization.
Am J Pathol. 2015 Apr;185(4):969-86.
Rat lens epithelial cells
5 μM
48 hours
To investigate the effect of CCG-203971 on TGFβ-induced EMT in lens epithelial cells. Results showed that CCG-203971 prevented TGFβ-induced nuclear accumulation of MRTF-A and αSMA expression.
Mol Med. 2016 Dec;22:713-723.
SK-Mel-147
10 μM
72 hours
Inhibits cellular migration and invasion, decreases MRTF target gene expression, and causes G1 cell cycle arrest
Mol Cancer Ther. 2017 Jan;16(1):193-204.
Human pulmonary artery endothelial cells (HPAECs)
5 mmol/L
72 hours
To evaluate the effect of CCG-203971 on PI hypoxia-induced senescence in HPAECs. Results showed that CCG-203971 treatment reduced the number of SA-β-gal positive cells, decreased p16INK4A gene expression and SASP factor concentrations (IL-1, TNF-α, and MCP1), improved HPAEC proliferation, and reduced the proportion of apoptotic cells.
Biomedicines. 2023 Aug 23;11(9):2351.
Human colonic fibroblast CCD-18co
1, 3, 10, 17.5, 25 μM
24 to 48 hours
CCG-203971 inhibited TGF-β-induced α SMA and collagen I protein expression and repressed the expression of MKL1, MYLK, ACTA2, and col1A1 genes at the transcriptional level.
Inflamm Bowel Dis. 2014 Jan;20(1):154-65.
MCF10A cells
20 μM
16-36 hours
Inhibition of the Rho/MRTF/SRF pathway, reducing protrusion formation of MCF10A cells on stiff matrices.
Cell Commun Signal. 2022 Oct 13;20(1):158.
C2C12 mouse myoblasts
20 µM
24 hours
To assess the effect of CCG-203971 on cell viability, results showed significant reduction in cell viability at 20 µM concentration.
Cells. 2024 Feb 24;13(5):392.
WI-38 human lung fibroblasts
20 µM
24 hours
To assess the effect of CCG-203971 on cell viability, results showed significant reduction in cell viability at 20 µM concentration.
Cells. 2024 Feb 24;13(5):392.
CCG-203971 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
C57BL/6 mice
Bleomycin-induced lung fibrosis model
Intraperitoneal injection
100 mg/kg
Twice daily, from day 11 to day 21
To assess the effect of CCG-203971 on lung fibrosis. Results showed that CCG-203971 significantly reduced lung collagen content and promoted myofibroblast apoptosis.
Am J Pathol. 2015 Apr;185(4):969-86.
Mice
Mammary acinar organoid model
In vitro culture
20 μM
16-36 hours
Inhibition of the Rho/MRTF/SRF pathway, reducing protrusion formation of mammary acinar organoids on stiff matrices.
Cell Commun Signal. 2022 Oct 13;20(1):158.
CBA/J mice
SL1344:CBA/J fibrosis model
Oral gavage
100 mg/kg/day
Twice daily for 7 days
To evaluate the anti-fibrotic efficacy of CCG-203971 in the SL1344:CBA/J fibrosis model. Results showed that CCG-203971 significantly repressed fibrotic genes COL1A1 and IGF-1, as well as inflammatory genes IL-1β and IL-6.
J Crohns Colitis. 2017 Jun 1;11(6):724-736
NOD SCID mice
Melanoma lung metastasis model
Intraperitoneal injection
100 mg/kg
Twice daily for 18 days
Significantly reduces the number and size of lung metastases, lowering total lung tumor burden
Mol Cancer Ther. 2017 Jan;16(1):193-204.
Mice
Bleomycin-induced skin fibrosis model
Oral gavage
50 mg/kg/day
Once daily for 14 days
Assessed the preventive effect of CCG-257081 on skin fibrosis, showing significant reduction in skin thickening and collagen content
Once on day 18, and twice per day on days 19 and 20
CCG-203971 inhibits the Rho-MRTF-SRF signaling pathway, enhancing the anti-tumor effects of chemotherapy and suppressing the migration of chemoresistant C1498 cells.
Inflamm Regen. 2020 Jul 6;40:15
Rats
PI hypoxia model
Intraperitoneal injection
0.15 mg/kg
Once daily for 21 days
To evaluate the effect of CCG-203971 on PI hypoxia-induced senescence and pulmonary arterial remodeling in lung tissue. Results showed that CCG-203971 treatment reduced senescence markers (SA-β-gal positive cells, p16INK4A gene expression, and SASP factor concentrations) and improved pulmonary arterial wall thickness, collagen fiber deposition, and smooth muscle hyperplasia.
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