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We have a deep understanding of the key factors of cyclosporin drug R & D. In this field, we have established the novel chemistry for synthesizing novel cyclosporin analogs. So far, many novel derivatives have been completed. We are currently a leading research group in the field of cyclosporin chemistry and able to provide the consulting services for the novel cyclosporin analog drug R & D.

Cyclosporin and analogs possess anti-viral (HIV and HCV) and anti-inflammatory activities. The analogs may also be useful in promoting hair growth and in the treatment of neurodegenerative diseases.

Extensive research has shown that cyclosporin A and its analogs inhibit cyclophilin and therefore have anti HIV activity (Cell, 1993, 73, 1067-1078; Nature, 1994, 372, 359-362; Nature, 1994, 372, 363-365; Antimicrob Agents Chemother. 1994, 38, 1763-1772; Cell, 1996, 87, 1285-1294; Nature Medicine, 2003, 9, 1138-1143; J. Biol. Chem. 2003, 278, 43202-43213).

Recently, it has been discovered that cyclosporins inhibit both HCV replicons and infectious viruses in vitro; its cellular target, cyclophilin (CyP) B plays a critical role in HCV genome replication (Molecular Cell, 2005, 19, 111-122). In addition, a clinical trial of cyclosporin A combined with interferon in the treatment of HCV patients in Japan confirmed that it is more effective than interferon monotherapy (J Gastroenterol 2003, 38, 567–572).

Non-immunosuppressive cyclosporin analog, NIM-811, Debio-025 and SCY-635 have been developed and are being tested in patients with chronic HCV infection.

In vitro testing, Debio-025 was found to be a potent inhibitor against HCV replication with a unique resistance profile; it was able to completely prevent the development of BILN-2061 and VX-950 resistant replicons (Antiviral Research, 2007, 74, A39).

In phase Ib trials, DEBIO-025 resulted in an average viral load reduction of 3.6 log10 (Hepatology, 2006, 44, 4S1, 609A). No viral rebounds were observed in patients while receiving DEBIO-025 monotherapy. Moreover, no selection for viral resistance to DEBIO-025 or another cyclophilin inhibitor, NIM-811 (Novartis compound), has been observed in patients to date (Update on New Hepatitis C Virus Therapies, 2007 Clinical Care Options, page 17; Program and abstracts of the 57th Annual Meeting of the American Association for the Study of Liver Diseases; October 27-31, 2006, Boston, Massachusetts, Abstract 1130; Hepatology. 2006, 43, 761-770; Program and abstracts of the 13th Conference on Retroviruses and Opportunistic Infections; February 5-8, 2006, Denver, Colorado, Abstract 516; Antimicrob Agents Chemother. 2006, 50, 2976-2982; Biochem Biophys Res Commun. 2006, 343, 879-884).

In phase II trials, results from a double-blind, placebo-controlled study of Debio-025 during 29 days in combination with Pegasys (pegylated Interferon alpha-2a) in HCV genotype 1 and 4 patients vs. treatment with Pegasys monotherapy were released. There were a total of 90 patients in the study. Results showed a 4.6 log10 decrease in HCV RNA in the 600 mg/day arm and a 4.8 log10 decrease in HCV RNA in 1000 mg/day arm. This compares to 2.49 log10 in the Pegasys plus placebo arm and 2.20 log10 decrease in HCV RNA in the Debio 1000 mg/day monotherapy arm (Cilinical Update – Debio 025 in Hepatitis C, Medical News Today, April 29, 2008; http://www.medicalnewstoday.com/articles/105591.php).

News of the 15-days phase 1b clinical trial for SCY-635 was released on April 27, 2009. SCY-635 was well-tolerated with no serious adverse events, no discontinuations, and no dose-limiting toxicities. At the dose of 900 mg/day arm tested in the study, SCY-635 exhibited clinically relevant antiviral activity. All treated patients showed a viral load reduction with a group mean maximum decrease of 2.2 log10 on the last day of the study (p<0.05 for the day 15 comparison).

Clearly, cyclosporin analogs have become very promising drug candidates for the treatment of HCV infections in combination with interferon or polymerase and protease inhibitors (Expert Opin. Investig. Drugs , 2007, 16, 1345-1354).

S & T Global’s founder has worked on cyclosporin drug R & D for many years. He has completed the challenging chemistry necessary for clinical cyclosporin analog production and for novel analog syntheses. So far, many cyclosporin analogs have been synthesized and the structure-activity relationship from such analogs have been established. Because of this, S & T Global possesses a special background and a unique expertise in conducting the complicated cyclosporin chemistry for drug R & D. We can provide the consulting services for cyclosporin drug R & D based on our deep understanding in this field.

Our work at a glance

(2006) Another non-immunosuppressive cyclosporin analog was synthesized.

(2005) A non-immunosuppressive cyclosporin analog was synthesized. This compound has a very good cyclophilin binding activity (IC50 is about 2-3 nM).

(2004) We tested our novel cyclosprorin analog for the first time for anti HCV activity. The cell assay completed in the South Research Institute proved that the compound was positive against HCV replication in the replicon cell.




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