CCG-222740 | CAS#1922098-69-8 | MRTF/SRF inhibitor

MedKoo Cat#: 555497 | Name: CCG-222740

Description:

WARNING: This product is for research use only, not for human or veterinary use.

CCG-222740 is a potent MRTF/SRF inhibitor. CCG-222740 markedly decreased SRF reporter gene activity and showed a greater inhibitory effect on MRTF/SRF target genes than the previously described MRTF-A inhibitor CCG-203971. CCG-222740 was also five times more potent, with an IC50 of 5 μM, in a fibroblast-mediated collagen contraction assay, was less cytotoxic, and a more potent inhibitor of alpha-smooth muscle actin protein expression than CCG-203971.

Chemical Structure

CCG-222740

CAS#1922098-69-8

Theoretical Analysis

MedKoo Cat#: 555497

Name: CCG-222740

CAS#: 1922098-69-8

Chemical Formula: C23H19ClF2N2O3

Exact Mass: 444.1052

Molecular Weight: 444.86

Elemental Analysis: C, 62.10; H, 4.31; Cl, 7.97; F, 8.54; N, 6.30; O, 10.79

Price and Availability

Size	Price	Availability
5mg	USD 110.00	Ready to ship
10mg	USD 190.00	Ready to ship
25mg	USD 350.00	Ready to ship
50mg	USD 550.00	Ready to ship
100mg	USD 950.00	Ready to ship
200mg	USD 1,650.00	Ready to ship
500mg	USD 2,850.00	Ready to ship
1g	USD 3,850.00	Ready to ship

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Related CAS #

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Synonym

CCG-222740; CCG 222740; CCG222740;

IUPAC/Chemical Name

N-(4-chlorophenyl)-5,5-difluoro-1-(3-(furan-2-yl)benzoyl)piperidine-3-carboxamide

InChi Key

PMTPYUTZAJWGPE-UHFFFAOYSA-N

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)

SMILES Code

O=C(C1CN(C(C2=CC=CC(C3=CC=CO3)=C2)=O)CC(F)(F)C1)NC4=CC=C(Cl)C=C4

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO

Shelf Life

>3 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Local delivery of CCG-222740 and CCG-203971 in a validated and clinically relevant rabbit model of scar tissue formation after glaucoma filtration surgery increased the long-term success of the surgery by 67% (P < 0.0005) and 33% (P < 0.01), respectively, and significantly decreased fibrosis and scarring histologically. Unlike mitomycin-C, neither CCG-222740 nor CCG-203971 caused any detectable epithelial toxicity or systemic side effects with very low drug levels measured in the aqueous, vitreous, and serum.

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#B20B02C06

QC Data

View QC data: current batch, Lot#B20B02C06

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

CCG-222740 is a Rho/myocardin-related transcription factor (MRTF) pathway inhibitor.

In vitro activity:

These results show that nanocarrier CCG-222740 formulation significantly decreased ACTA2 gene expression in human conjunctival fibroblasts by 63.0% (p = 0.0468), 61.0% (p = 0.0257) and 71.2% (p = 0.0327) at 2.5, 5 and 10 μM concentrations, respectively, compared to empty liposomes (Fig. 2a). There was a vehicle effect with empty liposomes also causing a decrease in the ACTA2 gene expression compared to untreated cells. Reference: J Nanobiotechnology. 2018; 16: 97. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6258153/

In vivo activity:

As shown by both western blotting and immunohistochemistry, CCG-222740 significantly reduced α-SMA levels in the pancreas of caerulein-stimulated KC mice (p < 0.05) (Fig. 4B,C, Sup Fig. 3). This downregulation occurred in the stellate cells surrounding the acinar structures (Fig. 4C, arrows point to PSCs), as confirmed by IHC. KC mice treated with CCG-222740 showed a significant upregulation in the percentage of CD4 T cells (CD45+, CD3+, CD4+) infiltrating into the pancreas (p = 0.03), 21.6% in the control vs. 27.4% in the treated group (Fig. 5A). A significant downregulation in the percentage of macrophages (CD45+, CD11b+, Gr1−) in the pancreas of treated KC mice (12.2%) compared with the control mice (14.4%) was also observed (p = 0.03), as determined by flow cytometry and immunohistochemistry (Fig. 5B). Reference: Sci Rep. 2019; 9: 7072. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6506531/

	Solvent	mg/mL	mM
Solubility
	DMSO	107.0	240.52
	Ethanol	89.0	200.06

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 444.86 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Tagalakis AD, Madaan S, Larsen SD, Neubig RR, Khaw PT, Rodrigues I, Goyal S, Lim KS, Yu-Wai-Man C. In vitro and in vivo delivery of a sustained release nanocarrier-based formulation of an MRTF/SRF inhibitor in conjunctival fibrosis. J Nanobiotechnology. 2018 Nov 27;16(1):97. doi: 10.1186/s12951-018-0425-3. PMID: 30482196; PMCID: PMC6258153. 2. Leal AS, Misek SA, Lisabeth EM, Neubig RR, Liby KT. The Rho/MRTF pathway inhibitor CCG-222740 reduces stellate cell activation and modulates immune cell populations in KrasG12D; Pdx1-Cre (KC) mice. Sci Rep. 2019 May 8;9(1):7072. doi: 10.1038/s41598-019-43430-0. PMID: 31068602; PMCID: PMC6506531. 3. Yu-Wai-Man C, Spencer-Dene B, Lee RMH, Hutchings K, Lisabeth EM, Treisman R, Bailly M, Larsen SD, Neubig RR, Khaw PT. Local delivery of novel MRTF/SRF inhibitors prevents scar tissue formation in a preclinical model of fibrosis. Sci Rep. 2017 Mar 31;7(1):518. doi: 10.1038/s41598-017-00212-w. PMID: 28364121; PMCID: PMC5428058.

In vitro protocol:

In vivo protocol:

1. Leal AS, Misek SA, Lisabeth EM, Neubig RR, Liby KT. The Rho/MRTF pathway inhibitor CCG-222740 reduces stellate cell activation and modulates immune cell populations in KrasG12D; Pdx1-Cre (KC) mice. Sci Rep. 2019 May 8;9(1):7072. doi: 10.1038/s41598-019-43430-0. PMID: 31068602; PMCID: PMC6506531. 2. Yu-Wai-Man C, Spencer-Dene B, Lee RMH, Hutchings K, Lisabeth EM, Treisman R, Bailly M, Larsen SD, Neubig RR, Khaw PT. Local delivery of novel MRTF/SRF inhibitors prevents scar tissue formation in a preclinical model of fibrosis. Sci Rep. 2017 Mar 31;7(1):518. doi: 10.1038/s41598-017-00212-w. PMID: 28364121; PMCID: PMC5428058.

1: Tagalakis AD, Madaan S, Larsen SD, Neubig RR, Khaw PT, Rodrigues I, Goyal S, Lim KS, Yu-Wai-Man C. In vitro and in vivo delivery of a sustained release nanocarrier-based formulation of an MRTF/SRF inhibitor in conjunctival fibrosis. J Nanobiotechnology. 2018 Nov 27;16(1):97. doi: 10.1186/s12951-018-0425-3. PubMed PMID: 30482196; PubMed Central PMCID: PMC6258153. 2: Yu-Wai-Man C, Spencer-Dene B, Lee RMH, Hutchings K, Lisabeth EM, Treisman R, Bailly M, Larsen SD, Neubig RR, Khaw PT. Local delivery of novel MRTF/SRF inhibitors prevents scar tissue formation in a preclinical model of fibrosis. Sci Rep. 2017 Mar 31;7(1):518. doi: 10.1038/s41598-017-00212-w. PubMed PMID: 28364121; PubMed Central PMCID: PMC5428058.