Target General Information |
Target ID |
T66505
|
Target Name |
Smoothened homolog (SMO) |
Gene Name |
SMO |
Species |
Homo sapiens |
UniProt ID |
SMO_HUMAN |
Sequence |
MAAARPARGPELPLLGLLLLLLLGDPGRGAASSGNATGPGPRSAGGSARRSAAVTGPPPP LSHCGRAAPCEPLRYNVCLGSVLPYGATSTLLAGDSDSQEEAHGKLVLWSGLRNAPRCWA VIQPLLCAVYMPKCENDRVELPSRTLCQATRGPCAIVERERGWPDFLRCTPDRFPEGCTN EVQNIKFNSSGQCEVPLVRTDNPKSWYEDVEGCGIQCQNPLFTEAEHQDMHSYIAAFGAV TGLCTLFTLATFVADWRNSNRYPAVILFYVNACFFVGSIGWLAQFMDGARREIVCRADGT MRLGEPTSNETLSCVIIFVIVYYALMAGVVWFVVLTYAWHTSFKALGTTYQPLSGKTSYF HLLTWSLPFVLTVAILAVAQVDGDSVSGICFVGYKNYRYRAGFVLAPIGLVLIVGGYFLI RGVMTLFSIKSNHPGLLSEKAASKINETMLRLGIFGFLAFGFVLITFSCHFYDFFNQAEW ERSFRDYVLCQANVTIGLPTKQPIPDCEIKNRPSLLVEKINLFAMFGTGIAMSTWVWTKA TLLIWRRTWCRLTGQSDDEPKRIKKSKMIAKAFSKRHELLQNPGQELSFSMHTVSHDGPV AGLAFDLNEPSADVSSAWAQHVTKMVARRGAILPQDISVTPVATPVPPEEQANLWLVEAE ISPELQKRLGRKKKRRKRKKEVCPLAPPPELHPPAPAPSTIPRLPQLPRQKCLVAAGAWG AGDSCRQGAWTLVSNPFCPEPSPPQDPFLPSAPAPVAWAHGRRQGLGPIHSRTNLMDTEL MDADSDF [Homo sapiens]
|
Drug and Corresponding Resistance Mutations |
Mutation Info |
Missense: A459V |
Drugs |
Drug Name |
Vismodegib |
Drug Info
|
[5] |
Targeted Disease |
Primitive Neuroectodermal Tumour Medulloblastoma |
Mutation Prevalence |
3 out of 12 patients |
|
Drug Name |
Vismodegib |
Drug Info
|
[5] |
Targeted Disease |
Basal Cell Carcinoma |
Mutation Prevalence |
3 out of 12 patients |
|
Mutation Info |
Missense: C469Y |
Drugs |
Drug Name |
Vismodegib |
Drug Info
|
[5] |
Targeted Disease |
Primitive Neuroectodermal Tumour Medulloblastoma |
Mutation Prevalence |
1 out of 12 patients |
|
Drug Name |
Vismodegib |
Drug Info
|
[5] |
Targeted Disease |
Basal Cell Carcinoma |
Mutation Prevalence |
1 out of 12 patients |
|
Mutation Info |
Missense: D473G |
Drugs |
Drug Name |
Vismodegib |
Drug Info
|
[2], [3] |
Targeted Disease |
Primitive Neuroectodermal Tumour Medulloblastoma |
Mutation Prevalence |
6 out of 14 patients |
|
Drug Name |
Vismodegib |
Drug Info
|
[2], [3] |
Targeted Disease |
Basal Cell Carcinoma |
Mutation Prevalence |
6 out of 14 patients |
|
Mutation Info |
Missense: D473H |
Drugs |
Drug Name |
Gdc-0449 |
Drug Info
|
[1] |
Targeted Disease |
Primitive Neuroectodermal Tumour Medulloblastoma |
|
Drug Name |
Gdc-0449 |
Drug Info
|
[1] |
Targeted Disease |
Basal Cell Carcinoma |
|
|
Mutation Info |
Missense: D473N |
Drugs |
Drug Name |
Vismodegib |
Drug Info
|
[3] |
Targeted Disease |
Primitive Neuroectodermal Tumour Medulloblastoma |
Mutation Prevalence |
1 out of 30 patients |
|
Drug Name |
Vismodegib |
Drug Info
|
[3] |
Targeted Disease |
Basal Cell Carcinoma |
Mutation Prevalence |
1 out of 30 patients |
|
Mutation Info |
Missense: D473Y |
Drugs |
Drug Name |
Vismodegib |
Drug Info
|
[2] |
Targeted Disease |
Primitive Neuroectodermal Tumour Medulloblastoma |
|
Drug Name |
Vismodegib |
Drug Info
|
[2] |
Targeted Disease |
Basal Cell Carcinoma |
|
Mutation Info |
Missense: F460L |
Drugs |
Drug Name |
Vismodegib |
Drug Info
|
[3] |
Targeted Disease |
Primitive Neuroectodermal Tumour Medulloblastoma |
Mutation Prevalence |
1 out of 30 patients |
|
Drug Name |
Vismodegib |
Drug Info
|
[3] |
Targeted Disease |
Basal Cell Carcinoma |
Mutation Prevalence |
1 out of 30 patients |
|
Mutation Info |
Missense: G497W |
Drugs |
Drug Name |
Vismodegib |
Drug Info
|
[2], [3] |
Targeted Disease |
Primitive Neuroectodermal Tumour Medulloblastoma |
|
Drug Name |
Vismodegib |
Drug Info
|
[2], [3] |
Targeted Disease |
Basal Cell Carcinoma |
|
Mutation Info |
Missense: H231R |
Drugs |
Drug Name |
Vismodegib |
Drug Info
|
[3] |
Targeted Disease |
Primitive Neuroectodermal Tumour Medulloblastoma |
Mutation Prevalence |
2 out of 30 patients |
|
Drug Name |
Vismodegib |
Drug Info
|
[3] |
Targeted Disease |
Basal Cell Carcinoma |
Mutation Prevalence |
2 out of 30 patients |
|
Mutation Info |
Missense: L412F |
Drugs |
Drug Name |
Vismodegib |
Drug Info
|
[2], [3] |
Targeted Disease |
Primitive Neuroectodermal Tumour Medulloblastoma |
|
Drug Name |
Vismodegib |
Drug Info
|
[2], [3] |
Targeted Disease |
Basal Cell Carcinoma |
|
Mutation Info |
Missense: Q477E |
Drugs |
Drug Name |
Vismodegib |
Drug Info
|
[2], [3] |
Targeted Disease |
Primitive Neuroectodermal Tumour Medulloblastoma |
Mutation Prevalence |
1 out of 30 patients |
|
Drug Name |
Vismodegib |
Drug Info
|
[2], [3] |
Targeted Disease |
Basal Cell Carcinoma |
Mutation Prevalence |
1 out of 30 patients |
|
Mutation Info |
Missense: S533N |
Drugs |
Drug Name |
Vismodegib |
Drug Info
|
[3] |
Targeted Disease |
Primitive Neuroectodermal Tumour Medulloblastoma |
|
Drug Name |
Vismodegib |
Drug Info
|
[3] |
Targeted Disease |
Basal Cell Carcinoma |
|
Mutation Info |
Missense: T241M |
Drugs |
Drug Name |
Vismodegib |
Drug Info
|
[5] |
Targeted Disease |
Primitive Neuroectodermal Tumour Medulloblastoma |
Mutation Prevalence |
1 out of 12 patients |
|
Drug Name |
Vismodegib |
Drug Info
|
[5] |
Targeted Disease |
Basal Cell Carcinoma |
Mutation Prevalence |
1 out of 12 patients |
|
Mutation Info |
Missense: V321A |
Drugs |
Drug Name |
Vismodegib |
Drug Info
|
[3] |
Targeted Disease |
Primitive Neuroectodermal Tumour Medulloblastoma |
Mutation Prevalence |
1 out of 30 patients |
|
Drug Name |
Vismodegib |
Drug Info
|
[3] |
Targeted Disease |
Basal Cell Carcinoma |
Mutation Prevalence |
1 out of 30 patients |
|
Mutation Info |
Missense: V321M |
Drugs |
Drug Name |
Vismodegib |
Drug Info
|
[4], [5] |
Targeted Disease |
Primitive Neuroectodermal Tumour Medulloblastoma |
Mutation Prevalence |
2 out of 12 patients |
|
Drug Name |
Vismodegib |
Drug Info
|
[4], [5] |
Targeted Disease |
Basal Cell Carcinoma |
Mutation Prevalence |
2 out of 12 patients |
|
Mutation Info |
Missense: W281C |
Drugs |
Drug Name |
Vismodegib |
Drug Info
|
[2], [3] |
Targeted Disease |
Primitive Neuroectodermal Tumour Medulloblastoma |
Mutation Prevalence |
2 out of 30 patients |
|
Drug Name |
Vismodegib |
Drug Info
|
[2], [3] |
Targeted Disease |
Basal Cell Carcinoma |
Mutation Prevalence |
2 out of 30 patients |
|
Mutation Info |
Missense: W281L |
Drugs |
Drug Name |
Vismodegib |
Drug Info
|
[4] |
Targeted Disease |
Primitive Neuroectodermal Tumour Medulloblastoma |
|
Drug Name |
Vismodegib |
Drug Info
|
[4] |
Targeted Disease |
Basal Cell Carcinoma |
|
Mutation Info |
Missense: W535L |
Drugs |
Drug Name |
Vismodegib |
Drug Info
|
[2], [3] |
Targeted Disease |
Primitive Neuroectodermal Tumour Medulloblastoma |
Mutation Prevalence |
4 out of 30 patients |
|
Drug Name |
Vismodegib |
Drug Info
|
[2], [3] |
Targeted Disease |
Basal Cell Carcinoma |
Mutation Prevalence |
4 out of 30 patients |
|
Mutation Info |
Missense: W535R |
Drugs |
Drug Name |
Vismodegib |
Drug Info
|
[3] |
Targeted Disease |
Primitive Neuroectodermal Tumour Medulloblastoma |
Mutation Prevalence |
4 out of 30 patients |
|
Drug Name |
Vismodegib |
Drug Info
|
[3] |
Targeted Disease |
Basal Cell Carcinoma |
Mutation Prevalence |
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.
|
REF 6 |
Hedgehog pathway inhibitor saridegib (IPI-926) increases lifespan in a mouse medulloblastoma model. Proc Natl Acad Sci U S A. 2012 May 15;109(20):7859-64.
|