Anti-ulcer agent teprenone inhibits hepatitis C virus replication: potential treatment for hepatitis

[Guest guest]

http://www.mdlinx.com/gastroenterology/newsl-article.cfm/3636199/ZZ6806553679256\

39220014/?news_id=511 & newsdt=060911 & subspec_id=144

Anti-ulcer agent teprenone inhibits hepatitis C virus replication: potential

treatment for hepatitis C

Liver International, 06/09/2011 Clinical Article

Ikeda M et al. - The anti-ulcer agent teprenone inhibited hepatitis C virus(HCV)

RNA replication and enhanced statins' inhibitory action against

geranylgeranylation. This newly discovered function of teprenone may improve the

treatment of HCV-associated liver diseases as an adjuvant to statins.

Methods

.. Geranyl compounds [geranylgeraniol, geranylgeranoic acid, vitamin K2 and

teprenone (Selbex)] for their effects on HCV RNA replication using genome-length

HCV RNA-replicating cells (the OR6 assay system) and a JFH-1 infection cell

culture system were tested.

.. Teprenone is the major component of the anti-ulcer agent, Selbex.

.. Anti-HCV activities of the geranyl compounds in combination with interferon

(IFN)-á or statins were also tested.

Results. Among the geranyl compounds tested, only teprenone exhibited anti-HCV

activity at a clinically achievable concentration.

.. However, other anti-ulcer agents tested had no inhibitory effect on HCV RNA

replication.

.. Combination of teprenone and IFN-á exhibited a strong inhibitory effect on HCV

RNA replication.

.. Although teprenone alone did not inhibit geranylgeranylation, surprisingly,

statins' inhibitory action against geranylgeranylation was enhanced by

cotreatment with teprenone.

________________________________________________________________________________

http://www.ingentaconnect.com/content/mksg/liv/2011/00000031/00000006/art00017

Anti-ulcer agent teprenone inhibits hepatitis C virus replication: potential

treatment for hepatitis C

Authors: Ikeda, Masanori1; Kawai, Yoshinari; Mori, Kyoko1; Yano, Masahiko; Abe,

Ken-ichi1; Nishimura, Go1; Dansako, Hiromichi1; Ariumi, Yasuo1; Wakita, Takaji2;

Yamamoto, Kazuhide3; Kato, Nobuyuki1

Source: Liver International, Volume 31, Number 6, July 2011 , pp. 871-880(10)

Publisher: Wiley-Blackwell

Abstract:

Background:

Previously we reported that 3-hydroxy-3-methylglutaryl coenzyme A reductase

inhibitors, statins, inhibited hepatitis C virus (HCV) RNA replication.

Furthermore, recent reports revealed that the statins are associated with a

reduced risk of hepatocellular carcinoma and lower portal pressure in patients

with cirrhosis. The statins exhibited anti-HCV activity by inhibiting

geranylgeranylation of host proteins essential for HCV RNA replication.

Geranylgeranyl pyrophosphate (GGPP) is a substrate for

geranylgeranyltransferase. Therefore, we examined the potential of geranyl

compounds with chemical structures similar to those of GGPP to inhibit HCV RNA

replication.

Methods:

We tested geranyl compounds [geranylgeraniol, geranylgeranoic acid, vitamin K2

and teprenone (Selbex)] for their effects on HCV RNA replication using

genome-length HCV RNA-replicating cells (the OR6 assay system) and a JFH-1

infection cell culture system. Teprenone is the major component of the

anti-ulcer agent, Selbex. We also examined the anti-HCV activities of the

geranyl compounds in combination with interferon (IFN)-á or statins.

Results:

Among the geranyl compounds tested, only teprenone exhibited anti-HCV activity

at a clinically achievable concentration. However, other anti-ulcer agents

tested had no inhibitory effect on HCV RNA replication. The combination of

teprenone and IFN-á exhibited a strong inhibitory effect on HCV RNA replication.

Although teprenone alone did not inhibit geranylgeranylation, surprisingly,

statins' inhibitory action against geranylgeranylation was enhanced by

cotreatment with teprenone.

Conclusions:

The anti-ulcer agent teprenone inhibited HCV RNA replication and enhanced

statins' inhibitory action against geranylgeranylation. This newly discovered

function of teprenone may improve the treatment of HCV-associated liver diseases

as an adjuvant to statins.

Document Type: Research article

DOI: 10.1111/j.1478-3231.2011.02499.x

Affiliations:

1: Department of Tumor Virology, Okayama University Graduate School of Medicine,

Dentistry, and Pharmaceutical Sciences, Okayama, Japan 2: Department of Virology

II, National Institute of Infectious Diseases, Tokyo, Japan 3: Department of

Gastroenterology and Hepatology, Okayama University Graduate School of Medicine,

Dentistry, and Pharmaceutical Sciences, Okayama, Japan

Publication date: 2011-07-01

[Guest guest]

http://www.mdlinx.com/gastroenterology/newsl-article.cfm/3636199/ZZ6806553679256\

39220014/?news_id=511 & newsdt=060911 & subspec_id=144

Anti-ulcer agent teprenone inhibits hepatitis C virus replication: potential

treatment for hepatitis C

Liver International, 06/09/2011 Clinical Article

Ikeda M et al. - The anti-ulcer agent teprenone inhibited hepatitis C virus(HCV)

RNA replication and enhanced statins' inhibitory action against

geranylgeranylation. This newly discovered function of teprenone may improve the

treatment of HCV-associated liver diseases as an adjuvant to statins.

Methods

.. Geranyl compounds [geranylgeraniol, geranylgeranoic acid, vitamin K2 and

teprenone (Selbex)] for their effects on HCV RNA replication using genome-length

HCV RNA-replicating cells (the OR6 assay system) and a JFH-1 infection cell

culture system were tested.

.. Teprenone is the major component of the anti-ulcer agent, Selbex.

.. Anti-HCV activities of the geranyl compounds in combination with interferon

(IFN)-á or statins were also tested.

Results. Among the geranyl compounds tested, only teprenone exhibited anti-HCV

activity at a clinically achievable concentration.

.. However, other anti-ulcer agents tested had no inhibitory effect on HCV RNA

replication.

.. Combination of teprenone and IFN-á exhibited a strong inhibitory effect on HCV

RNA replication.

.. Although teprenone alone did not inhibit geranylgeranylation, surprisingly,

statins' inhibitory action against geranylgeranylation was enhanced by

cotreatment with teprenone.

________________________________________________________________________________

http://www.ingentaconnect.com/content/mksg/liv/2011/00000031/00000006/art00017

Anti-ulcer agent teprenone inhibits hepatitis C virus replication: potential

treatment for hepatitis C

Authors: Ikeda, Masanori1; Kawai, Yoshinari; Mori, Kyoko1; Yano, Masahiko; Abe,

Ken-ichi1; Nishimura, Go1; Dansako, Hiromichi1; Ariumi, Yasuo1; Wakita, Takaji2;

Yamamoto, Kazuhide3; Kato, Nobuyuki1

Source: Liver International, Volume 31, Number 6, July 2011 , pp. 871-880(10)

Publisher: Wiley-Blackwell

Abstract:

Background:

Previously we reported that 3-hydroxy-3-methylglutaryl coenzyme A reductase

inhibitors, statins, inhibited hepatitis C virus (HCV) RNA replication.

Furthermore, recent reports revealed that the statins are associated with a

reduced risk of hepatocellular carcinoma and lower portal pressure in patients

with cirrhosis. The statins exhibited anti-HCV activity by inhibiting

geranylgeranylation of host proteins essential for HCV RNA replication.

Geranylgeranyl pyrophosphate (GGPP) is a substrate for

geranylgeranyltransferase. Therefore, we examined the potential of geranyl

compounds with chemical structures similar to those of GGPP to inhibit HCV RNA

replication.

Methods:

We tested geranyl compounds [geranylgeraniol, geranylgeranoic acid, vitamin K2

and teprenone (Selbex)] for their effects on HCV RNA replication using

genome-length HCV RNA-replicating cells (the OR6 assay system) and a JFH-1

infection cell culture system. Teprenone is the major component of the

anti-ulcer agent, Selbex. We also examined the anti-HCV activities of the

geranyl compounds in combination with interferon (IFN)-á or statins.

Results:

Among the geranyl compounds tested, only teprenone exhibited anti-HCV activity

at a clinically achievable concentration. However, other anti-ulcer agents

tested had no inhibitory effect on HCV RNA replication. The combination of

teprenone and IFN-á exhibited a strong inhibitory effect on HCV RNA replication.

Although teprenone alone did not inhibit geranylgeranylation, surprisingly,

statins' inhibitory action against geranylgeranylation was enhanced by

cotreatment with teprenone.

Conclusions:

The anti-ulcer agent teprenone inhibited HCV RNA replication and enhanced

statins' inhibitory action against geranylgeranylation. This newly discovered

function of teprenone may improve the treatment of HCV-associated liver diseases

as an adjuvant to statins.

Document Type: Research article

DOI: 10.1111/j.1478-3231.2011.02499.x

Affiliations:

1: Department of Tumor Virology, Okayama University Graduate School of Medicine,

Dentistry, and Pharmaceutical Sciences, Okayama, Japan 2: Department of Virology

II, National Institute of Infectious Diseases, Tokyo, Japan 3: Department of

Gastroenterology and Hepatology, Okayama University Graduate School of Medicine,

Dentistry, and Pharmaceutical Sciences, Okayama, Japan

Publication date: 2011-07-01