Drug General Information
Drug ID D00TLP
Drug Name Simeprevir
Synonyms TMC436
Drug Type Small molecular drug
Therapeutic Class Antiinfective Agents
Company Johnson & Johnson
Structure D00TLP
Drug Resistance Mutations
Target Name HCV Serine protease (NS3) Target Info
Gene Name NS3
Uniprot ID POLG_HCVJA(1027-1657)
Species Hepatitis C virus genotype 1b
Reference Sequence APITAYSQQTRGLLGCIITSLTGRDKNQVDGEVQVLSTATQSFLATCVNGVCWTVYHGAG
SKTLAGPKGPITQMYTNVDQDLVGWPAPPGARSMTPCTCGSSDLYLVTRHADVVPVRRRG
DSRGSLLSPRPISYLKGSSGGPLLCPSGHVVGIFRAAVCTRGVAKAVDFIPVESMETTMR
SPVFTDNSSPPAVPQTFQVAHLHAPTGSGKSTKVPAAYAAQGYKVLVLNPSVAATLGFGA
YMSKAHGIEPNIRTGVRTITTGGPITYSTYCKFLADGGCSGGAYDIIICDECHSTDSTTI
LGIGTVLDQAETAGARLVVLATATPPGSITVPHPNIEEVALSNTGEIPFYGKAIPIEAIK
GGRHLIFCHSKKKCDELAAKLTGLGLNAVAYYRGLDVSVIPTSGDVVVVATDALMTGFTG
DFDSVIDCNTCVTQTVDFSLDPTFTIETTTLPQDAVSRAQRRGRTGRGRSGIYRFVTPGE
RPSGMFDSSVLCECYDAGCAWYELTPAETSVRLRAYLNTPGLPVCQDHLEFWESVFTGLT
HIDAHFLSQTKQAGDNLPYLVAYQATVCARAQAPPPSWDQMWKCLIRLKPTLHGPTPLLY
RLGAVQNEVTLTHPITKYIMACMSADLEVVT [Hepatitis C virus genotype
1b]
Targeted Disease HCV infection
Drug Resistance Mutations
Mutation info Missense: A156G [1]
Mutation Frequency 18% of the patiens
Level of Resistance Confer 19 fold resistance
Mutation info Missense: A156T [1]
Level of Resistance Confer 37 fold resistance
Mutation info Missense: A156V [1]
Level of Resistance Confer 196 fold resistance
Mutation info Missense: D168A [1]
Level of Resistance Confer 784 fold resistance
Mutation info Missense: D168E [1]
Mutation Frequency 86 out of 109 sequences
Level of Resistance Confer 38 fold resistance
Mutation info Missense: D168H [1]
Mutation Frequency 86 out of 109 sequences
Level of Resistance Confer 401 fold resistance
Mutation info Missense: D168I [1]
Mutation Frequency 86 out of 109 sequences
Level of Resistance Confer 1800 fold resistance
Mutation info Missense: D168N [1]
Mutation Frequency 86 out of 109 sequences
Level of Resistance Confer 5.5 fold resistance
Mutation info Missense: D168T [1]
Mutation Frequency 86 out of 109 sequences
Level of Resistance Confer 334 fold resistance
Mutation info Missense: D168V [1]
Mutation Frequency 86 out of 109 sequences
Level of Resistance Confer 3100 fold resistance
Mutation info Missense: D168Y [1]
Mutation Frequency 86 out of 109 sequences
Level of Resistance Confer 651 fold resistance
Mutation info Missense: F43I [1]
Level of Resistance Confer 89 fold resistance
Mutation info Missense: F43S + D168E [1]
Level of Resistance Confer 792 fold resistance
Mutation info Missense: F43S + Q80R [1]
Level of Resistance Confer 286 fold resistance
Mutation info Missense: F43S [1]
Level of Resistance Confer 11 fold resistance
Mutation info Missense: F43V [1]
Level of Resistance Confer 99 fold resistance
Mutation info Missense: Q41R [1]
Level of Resistance Confer 1.9 fold resistance
Mutation info Missense: Q80H + D168E [1]
Level of Resistance Confer 145 fold resistance
Mutation info Missense: Q80H [1]
Level of Resistance Confer 3.4 fold resistance
Mutation info Missense: Q80K + R155K [1]
Level of Resistance Confer 420 fold resistance
Mutation info Missense: Q80K [1]
Level of Resistance Confer 7.8 fold resistance
Mutation info Missense: Q80R + D168A [1]
Level of Resistance Confer 2660 fold resistance
Mutation info Missense: Q80R + D168E [1]
Level of Resistance Confer 453 fold resistance
Mutation info Missense: Q80R + R155K [1]
Level of Resistance Confer 305 fold resistance
Mutation info Missense: Q80R [1]
Level of Resistance Confer 6.4 fold resistance
Mutation info Missense: R109K [1]
Level of Resistance Confer 0.5 fold resistance
Mutation info Missense: R155K [1]
Level of Resistance Confer 32 fold resistance
Mutation info Missense: S122A [1]
Level of Resistance Confer 0.9 fold resistance
Mutation info Missense: S122G [1]
Level of Resistance Confer 0.5 fold resistance
Mutation info Missense: S122R [1]
Level of Resistance Confer 21 fold resistance
References
REF 1 In vitro resistance profile of the hepatitis C virus NS3/4A protease inhibitor TMC435. Antimicrob Agents Chemother. 2010 May;54(5):1878-87.

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