| Drug General Information |
| Drug ID |
D03EDQ
|
| Drug Name |
Vismodegib |
|
| Synonyms |
879085-55-9; GDC-0449; Erivedge; 2-chloro-N-(4-chloro-3-(pyridin-2-yl)phenyl)-4-(methylsulfonyl)benzamide; Vismodegib (GDC-0449); HhAntag691; GDC0449; GDC 0449; UNII-25X868M3DS; CHEMBL473417; CHEBI:66903; 25X868M3DS; NSC755986; AK-77261; 2-chloro-N-[4-chloro-3-(pyridin-2-yl)phenyl]-4-(methylsulfonyl)benzamide; C19H14Cl2N2O3S; 2-chloro-N-(4-chloro-3-pyridin-2-ylphenyl)-4-methylsulfonylbenzamide; 2-chloro-n-(4-chloro-3-(2-pyridinyl)phenyl)-4-(methylsulfonyl)benzamide; Erivedge (TN); Vismodegib (SHH inhibitor); Gdc-0449 |
| Drug Type |
Small molecular drug |
| Company |
Genentech |
| Structure |
|
| Drug Resistance Mutations |
| Target Name |
Smoothened homolog (SMO) |
Target Info |
| Gene Name |
SMO |
| Uniprot ID |
SMO_HUMAN |
| Species |
Homo sapiens |
| Reference Sequence |
MAAARPARGPELPLLGLLLLLLLGDPGRGAASSGNATGPGPRSAGGSARRSAAVTGPPPP
LSHCGRAAPCEPLRYNVCLGSVLPYGATSTLLAGDSDSQEEAHGKLVLWSGLRNAPRCWA
VIQPLLCAVYMPKCENDRVELPSRTLCQATRGPCAIVERERGWPDFLRCTPDRFPEGCTN
EVQNIKFNSSGQCEVPLVRTDNPKSWYEDVEGCGIQCQNPLFTEAEHQDMHSYIAAFGAV
TGLCTLFTLATFVADWRNSNRYPAVILFYVNACFFVGSIGWLAQFMDGARREIVCRADGT
MRLGEPTSNETLSCVIIFVIVYYALMAGVVWFVVLTYAWHTSFKALGTTYQPLSGKTSYF
HLLTWSLPFVLTVAILAVAQVDGDSVSGICFVGYKNYRYRAGFVLAPIGLVLIVGGYFLI
RGVMTLFSIKSNHPGLLSEKAASKINETMLRLGIFGFLAFGFVLITFSCHFYDFFNQAEW
ERSFRDYVLCQANVTIGLPTKQPIPDCEIKNRPSLLVEKINLFAMFGTGIAMSTWVWTKA
TLLIWRRTWCRLTGQSDDEPKRIKKSKMIAKAFSKRHELLQNPGQELSFSMHTVSHDGPV
AGLAFDLNEPSADVSSAWAQHVTKMVARRGAILPQDISVTPVATPVPPEEQANLWLVEAE
ISPELQKRLGRKKKRRKRKKEVCPLAPPPELHPPAPAPSTIPRLPQLPRQKCLVAAGAWG
AGDSCRQGAWTLVSNPFCPEPSPPQDPFLPSAPAPVAWAHGRRQGLGPIHSRTNLMDTEL
MDADSDF [Homo sapiens]
|
| Targeted Disease |
Medulloblastoma |
| Drug Resistance Mutations |
| Mutation info |
Missense: D473H |
[1] |
|
| Mutation info |
Missense: D473G |
[2], [3] |
| Mutation Frequency |
6 out of 14 patients |
|
| Mutation info |
Missense: L412F |
[2], [3] |
|
| Mutation info |
Missense: Q477E |
[2], [3] |
| Mutation Frequency |
1 out of 30 patients |
|
| Mutation info |
Missense: W281C |
[2], [3] |
| Mutation Frequency |
2 out of 30 patients |
|
| Mutation info |
Missense: W535L |
[2], [3] |
| Mutation Frequency |
4 out of 30 patients |
|
| Mutation info |
Missense: V321M |
[4], [5] |
| Mutation Frequency |
2 out of 12 patients |
|
| Mutation info |
Missense: G497W |
[2], [3] |
|
| Mutation info |
Missense: W281L |
[4] |
|
| Mutation info |
Missense: D473Y |
[2] |
|
| Mutation info |
Missense: A459V |
[5] |
| Mutation Frequency |
3 out of 12 patients |
|
| Mutation info |
Missense: C469Y |
[5] |
| Mutation Frequency |
1 out of 12 patients |
|
| Mutation info |
Missense: T241M |
[5] |
| Mutation Frequency |
1 out of 12 patients |
|
| Mutation info |
Missense: D473N |
[3] |
| Mutation Frequency |
1 out of 30 patients |
|
| Mutation info |
Missense: F460L |
[3] |
| Mutation Frequency |
1 out of 30 patients |
|
| Mutation info |
Missense: H231R |
[3] |
| Mutation Frequency |
2 out of 30 patients |
|
| Mutation info |
Missense: S533N |
[3] |
|
| Mutation info |
Missense: V321A |
[3] |
| Mutation Frequency |
1 out of 30 patients |
|
| Mutation info |
Missense: W535R |
[3] |
| Mutation Frequency |
4 out of 30 patients |
|
| Mutation info |
Missense: D473H |
[1] |
|
| Mutation info |
Missense: D473G |
[2], [3] |
| Mutation Frequency |
6 out of 14 patients |
|
| Mutation info |
Missense: L412F |
[2], [3] |
|
| Mutation info |
Missense: Q477E |
[2], [3] |
| Mutation Frequency |
1 out of 30 patients |
|
| Mutation info |
Missense: W281C |
[2], [3] |
| Mutation Frequency |
2 out of 30 patients |
|
| Mutation info |
Missense: W535L |
[2], [3] |
| Mutation Frequency |
4 out of 30 patients |
|
| Mutation info |
Missense: V321M |
[4], [5] |
| Mutation Frequency |
2 out of 12 patients |
|
| Mutation info |
Missense: G497W |
[2], [3] |
|
| Mutation info |
Missense: W281L |
[4] |
|
| Mutation info |
Missense: D473Y |
[2] |
|
| Mutation info |
Missense: A459V |
[5] |
| Mutation Frequency |
3 out of 12 patients |
|
| Mutation info |
Missense: C469Y |
[5] |
| Mutation Frequency |
1 out of 12 patients |
|
| Mutation info |
Missense: T241M |
[5] |
| Mutation Frequency |
1 out of 12 patients |
|
| Mutation info |
Missense: D473N |
[3] |
| Mutation Frequency |
1 out of 30 patients |
|
| Mutation info |
Missense: F460L |
[3] |
| Mutation Frequency |
1 out of 30 patients |
|
| Mutation info |
Missense: H231R |
[3] |
| Mutation Frequency |
2 out of 30 patients |
|
| Mutation info |
Missense: S533N |
[3] |
|
| Mutation info |
Missense: V321A |
[3] |
| Mutation Frequency |
1 out of 30 patients |
|
| Mutation info |
Missense: W535R |
[3] |
| Mutation Frequency |
4 out of 30 patients |
|
| References |
| REF 1 |
Smoothened mutation confers resistance to a Hedgehog pathway inhibitor in medulloblastoma. Science. 2009 Oct 23;326(5952):572-4.
|
| REF 2 |
Smoothened (SMO) receptor mutations dictate resistance to vismodegib in basal cell carcinoma. Mol Oncol. 2015 Feb;9(2):389-97.
|
| REF 3 |
Smoothened variants explain the majority of drug resistance in basal cell carcinoma. Cancer Cell. 2015 Mar 9;27(3):342-53.
|
| REF 4 |
Acquired resistance to the Hedgehog pathway inhibitor vismodegib due to smoothened mutations in treatment of locally advanced basal cell carcinoma. J Am Acad Dermatol. 2014 Nov;71(5):1005-8.
|
| REF 5 |
Genomic analysis of smoothened inhibitor resistance in basal cell carcinoma. Cancer Cell. 2015 Mar 9;27(3):327-41.
|
