Identification of GSK625433: A novel clinical candidate for the treatment of hepatitis C.

David Haigh; E.M. Amphlett; G.S. Bravi; H. Bright; V. Chung; C.L. Chambers; A.G. Cheasty; M.A. Convery; M.R. Ellis; R. Fenwick; D.F. Gray; C.D. Hartley; P.D. Howes; R.L. Jarvest; K.J. Medhurst; A. Mehbob; D. Mesogiti; F. Mirzai; F. Nerozzi; N.R. Parry; N. Roughley; T. Skarzynski; M.J. Slater; S.A. Smith; R. Stocker; C.J. Theobald; P.J. Thomas; P.A. Thommes; J.H. Thorpe; C.S. Wilkinson; E. Williams

Identification of GSK625433: A novel clinical candidate for the treatment of hepatitis C.

David Haigh, E.M. Amphlett, G.S. Bravi, H. Bright, V. Chung, C.L. Chambers, A.G. Cheasty, M.A. Convery, M.R. Ellis, R. Fenwick, D.F. Gray, C.D. Hartley, P.D. Howes, R.L. Jarvest, K.J. Medhurst, A. Mehbob, D. Mesogiti, F. Mirzai, F. Nerozzi, N.R. ParryN. Roughley, T. Skarzynski, M.J. Slater, S.A. Smith, R. Stocker, C.J. Theobald, P.J. Thomas, P.A. Thommes, J.H. Thorpe, C.S. Wilkinson, E. Williams

Research output: Contribution to journal › Article › peer-review

Abstract

Hepatitis C is an infection of the liver caused by a pos. single-stranded RNA virus (HCV) which affects 170 million people worldwide. It is responsible for 40-60% of all liver disease and is the major cause of liver transplants in the United States. The HCV NS5B gene encodes the viral RNA-dependent RNA polymerase which is essential for HCV replication. We have previously reported the identification of acylpyrrolidines as potent inhibitors of NS5B; however their activity is attenuated against genotype 1a. The design of improved broader-spectrum compds., capable of effective inhibition of both genotypes 1b and 1a is desirable. An understanding of the binding site and genotype sequence differences was utilized to design compds. with greatly enhanced genotype 1a and 1b potency. Our studies led to the identification of GSK625433, a potent, homochiral inhibitor of these HCV genotypes in both enzyme and sub-genomic replicon cell-based assays. GSK625433 has a good pharmacokinetic profile in pre-clin. animal species, enabling progression to clin. evaluation.

Original language	English
Pages (from-to)	MEDI-015-MEDI-015
Number of pages	1
Journal	Abstracts Of Papers Of The American Chemical Society
Volume	233
Publication status	Published - 2007

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Cite this

Haigh, D., Amphlett, E. M., Bravi, G. S., Bright, H., Chung, V., Chambers, C. L., Cheasty, A. G., Convery, M. A., Ellis, M. R., Fenwick, R., Gray, D. F., Hartley, C. D., Howes, P. D., Jarvest, R. L., Medhurst, K. J., Mehbob, A., Mesogiti, D., Mirzai, F., Nerozzi, F., ... Williams, E. (2007). Identification of GSK625433: A novel clinical candidate for the treatment of hepatitis C. Abstracts Of Papers Of The American Chemical Society, 233, MEDI-015-MEDI-015.

@article{e28d2684e47f49c5a8613db8a0882040,

title = "Identification of GSK625433: A novel clinical candidate for the treatment of hepatitis C.",

abstract = "Hepatitis C is an infection of the liver caused by a pos. single-stranded RNA virus (HCV) which affects 170 million people worldwide. It is responsible for 40-60% of all liver disease and is the major cause of liver transplants in the United States. The HCV NS5B gene encodes the viral RNA-dependent RNA polymerase which is essential for HCV replication. We have previously reported the identification of acylpyrrolidines as potent inhibitors of NS5B; however their activity is attenuated against genotype 1a. The design of improved broader-spectrum compds., capable of effective inhibition of both genotypes 1b and 1a is desirable. An understanding of the binding site and genotype sequence differences was utilized to design compds. with greatly enhanced genotype 1a and 1b potency. Our studies led to the identification of GSK625433, a potent, homochiral inhibitor of these HCV genotypes in both enzyme and sub-genomic replicon cell-based assays. GSK625433 has a good pharmacokinetic profile in pre-clin. animal species, enabling progression to clin. evaluation.",

author = "David Haigh and E.M. Amphlett and G.S. Bravi and H. Bright and V. Chung and C.L. Chambers and A.G. Cheasty and M.A. Convery and M.R. Ellis and R. Fenwick and D.F. Gray and C.D. Hartley and P.D. Howes and R.L. Jarvest and K.J. Medhurst and A. Mehbob and D. Mesogiti and F. Mirzai and F. Nerozzi and N.R. Parry and N. Roughley and T. Skarzynski and M.J. Slater and S.A. Smith and R. Stocker and C.J. Theobald and P.J. Thomas and P.A. Thommes and J.H. Thorpe and C.S. Wilkinson and E. Williams",

year = "2007",

language = "English",

volume = "233",

pages = "MEDI--015--MEDI--015",

journal = "Abstracts Of Papers Of The American Chemical Society",

publisher = "American Chemical Society",

}

Haigh, D, Amphlett, EM, Bravi, GS, Bright, H, Chung, V, Chambers, CL, Cheasty, AG, Convery, MA, Ellis, MR, Fenwick, R, Gray, DF, Hartley, CD, Howes, PD, Jarvest, RL, Medhurst, KJ, Mehbob, A, Mesogiti, D, Mirzai, F, Nerozzi, F, Parry, NR, Roughley, N, Skarzynski, T, Slater, MJ, Smith, SA, Stocker, R, Theobald, CJ, Thomas, PJ, Thommes, PA, Thorpe, JH, Wilkinson, CS & Williams, E 2007, 'Identification of GSK625433: A novel clinical candidate for the treatment of hepatitis C.', Abstracts Of Papers Of The American Chemical Society, vol. 233, pp. MEDI-015-MEDI-015.

TY - JOUR

T1 - Identification of GSK625433: A novel clinical candidate for the treatment of hepatitis C.

AU - Haigh, David

AU - Amphlett, E.M.

AU - Bravi, G.S.

AU - Bright, H.

AU - Chung, V.

AU - Chambers, C.L.

AU - Cheasty, A.G.

AU - Convery, M.A.

AU - Ellis, M.R.

AU - Fenwick, R.

AU - Gray, D.F.

AU - Hartley, C.D.

AU - Howes, P.D.

AU - Jarvest, R.L.

AU - Medhurst, K.J.

AU - Mehbob, A.

AU - Mesogiti, D.

AU - Mirzai, F.

AU - Nerozzi, F.

AU - Parry, N.R.

AU - Roughley, N.

AU - Skarzynski, T.

AU - Slater, M.J.

AU - Smith, S.A.

AU - Stocker, R.

AU - Theobald, C.J.

AU - Thomas, P.J.

AU - Thommes, P.A.

AU - Thorpe, J.H.

AU - Wilkinson, C.S.

AU - Williams, E.

PY - 2007

Y1 - 2007

N2 - Hepatitis C is an infection of the liver caused by a pos. single-stranded RNA virus (HCV) which affects 170 million people worldwide. It is responsible for 40-60% of all liver disease and is the major cause of liver transplants in the United States. The HCV NS5B gene encodes the viral RNA-dependent RNA polymerase which is essential for HCV replication. We have previously reported the identification of acylpyrrolidines as potent inhibitors of NS5B; however their activity is attenuated against genotype 1a. The design of improved broader-spectrum compds., capable of effective inhibition of both genotypes 1b and 1a is desirable. An understanding of the binding site and genotype sequence differences was utilized to design compds. with greatly enhanced genotype 1a and 1b potency. Our studies led to the identification of GSK625433, a potent, homochiral inhibitor of these HCV genotypes in both enzyme and sub-genomic replicon cell-based assays. GSK625433 has a good pharmacokinetic profile in pre-clin. animal species, enabling progression to clin. evaluation.

AB - Hepatitis C is an infection of the liver caused by a pos. single-stranded RNA virus (HCV) which affects 170 million people worldwide. It is responsible for 40-60% of all liver disease and is the major cause of liver transplants in the United States. The HCV NS5B gene encodes the viral RNA-dependent RNA polymerase which is essential for HCV replication. We have previously reported the identification of acylpyrrolidines as potent inhibitors of NS5B; however their activity is attenuated against genotype 1a. The design of improved broader-spectrum compds., capable of effective inhibition of both genotypes 1b and 1a is desirable. An understanding of the binding site and genotype sequence differences was utilized to design compds. with greatly enhanced genotype 1a and 1b potency. Our studies led to the identification of GSK625433, a potent, homochiral inhibitor of these HCV genotypes in both enzyme and sub-genomic replicon cell-based assays. GSK625433 has a good pharmacokinetic profile in pre-clin. animal species, enabling progression to clin. evaluation.

M3 - Article

VL - 233

SP - MEDI-015-MEDI-015

JO - Abstracts Of Papers Of The American Chemical Society

JF - Abstracts Of Papers Of The American Chemical Society

ER -

Identification of GSK625433: A novel clinical candidate for the treatment of hepatitis C.

Abstract

UN SDGs

Fingerprint

Cite this