| Drug General Information |
| Drug ID |
D00TLP
|
| Drug Name |
Simeprevir |
|
| Synonyms |
TMC436 |
| Drug Type |
Small molecular drug |
| Therapeutic Class |
Antiinfective Agents |
| Company |
Johnson & Johnson |
| Structure |
|
| 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.
|
