Home
Resources
Publications
Pharmacokinetic Optimitzation of CCG-203971: Novel Inhibitors of the Rho/MRTF/SRF Transcriptional Pathway as Potential Antifibrotic Therapeutics for Systemic Scleroderma

Pharmacokinetic Optimitzation of CCG-203971: Novel Inhibitors of the Rho/MRTF/SRF Transcriptional Pathway as Potential Antifibrotic Therapeutics for Systemic Scleroderma

Kim M Hutchings, Erika M Lisabeth, Walajapet Rajeswaran, Michael W Wilson, Roderick J Sorenson, Phillip L Campbell, Jeffrey H Ruth, Asif Amin, Pei-Suen Tsou, Jeffrey R Leipprandt, Samuel R Olson, Bo Wen, etc.

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

PMID: 28285914

Abstract:

We recently reported the development of a novel inhibitor of Rho-mediated gene transcription (1, CCG-203971) that is efficacious in multiple animal models of acute fibrosis, including scleroderma, when given intraperitoneally. The modest in vivo potency and poor pharmacokinetics (PK) of this lead, however, make it unsuitable for long term efficacy studies. We therefore undertook a systematic medicinal chemistry effort to improve both the metabolic stability and the solubility of 1, resulting in the identification of two analogs achieving over 10-fold increases in plasma exposures in mice. We subsequently showed that one of these analogs (8f, CCG-232601) could inhibit the development of bleomycin-induced dermal fibrosis in mice when administered orally at 50mg/kg, an effect that was comparable to what we had observed earlier with 1 at a 4-fold higher IP dose.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP1443437748	CCG-203971		1443437-74-8	Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: