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
Drug Name Saridegib Drug Info [6]
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.

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