Resistance mutation info of target

Target General Information
Target ID T66505
Target Name Smoothened homolog (SMO) Target Info
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 Resistance Mutation and Corresponding Drugs
Ref 542991(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 8198).
Ref 548818Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800029135)
Ref 532210Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
Ref 542006(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6975).
Ref 1572601A phase II, multicenter, open-label, 3-cohort trial evaluating the efficacy and safety of vismodegib in operable basal cell carcinoma.
Mutation Info Missense: A459V
Drugs
Drug Name Vismodegib Drug Info [556053]
Targeted Disease Basal Cell Carcinoma
Mutation Prevalence 3 out of 12 patients
Mutation Info Missense: C469Y
Drugs
Drug Name Vismodegib Drug Info [556053]
Targeted Disease Basal Cell Carcinoma
Mutation Prevalence 1 out of 12 patients
Mutation Info Missense: D473G
Drugs
Drug Name Vismodegib Drug Info [556033], [556054]
Targeted Disease Basal Cell Carcinoma
Mutation Prevalence 6 out of 14 patients
Mutation Info Missense: D473H
Drugs
Drug Name Saridegib Drug Info [555858]
Targeted Disease Cancer
Drug Name Gdc-0449 Drug Info [555729]
Targeted Disease Primitive Neuroectodermal Tumour Medulloblastoma
Mutation Info Missense: D473N
Drugs
Drug Name Vismodegib Drug Info [556054]
Targeted Disease Basal Cell Carcinoma
Mutation Prevalence 1 out of 30 patients
Mutation Info Missense: D473Y
Drugs
Drug Name Vismodegib Drug Info [556033]
Targeted Disease Basal Cell Carcinoma
Mutation Info Missense: F460L
Drugs
Drug Name Vismodegib Drug Info [556054]
Targeted Disease Basal Cell Carcinoma
Mutation Prevalence 1 out of 30 patients
Mutation Info Missense: G497W
Drugs
Drug Name Vismodegib Drug Info [556033], [556054]
Targeted Disease Basal Cell Carcinoma
Mutation Info Missense: H231R
Drugs
Drug Name Vismodegib Drug Info [556054]
Targeted Disease Basal Cell Carcinoma
Mutation Prevalence 2 out of 30 patients
Mutation Info Missense: L412F
Drugs
Drug Name Vismodegib Drug Info [556033], [556054]
Targeted Disease Basal Cell Carcinoma
Mutation Info Missense: Q477E
Drugs
Drug Name Vismodegib Drug Info [556033], [556054]
Targeted Disease Basal Cell Carcinoma
Mutation Prevalence 1 out of 30 patients
Mutation Info Missense: S533N
Drugs
Drug Name Vismodegib Drug Info [556054]
Targeted Disease Basal Cell Carcinoma
Mutation Info Missense: T241M
Drugs
Drug Name Vismodegib Drug Info [556053]
Targeted Disease Basal Cell Carcinoma
Mutation Prevalence 1 out of 12 patients
Mutation Info Missense: V321A
Drugs
Drug Name Vismodegib Drug Info [556054]
Targeted Disease Basal Cell Carcinoma
Mutation Prevalence 1 out of 30 patients
Mutation Info Missense: V321M
Drugs
Drug Name Vismodegib Drug Info [556027], [556053]
Targeted Disease Basal Cell Carcinoma
Mutation Prevalence 2 out of 12 patients
Mutation Info Missense: W281C
Drugs
Drug Name Vismodegib Drug Info [556033], [556054]
Targeted Disease Basal Cell Carcinoma
Mutation Prevalence 2 out of 30 patients
Mutation Info Missense: W281L
Drugs
Drug Name Vismodegib Drug Info [556027]
Targeted Disease Basal Cell Carcinoma
Mutation Info Missense: W535L
Drugs
Drug Name Vismodegib Drug Info [556033], [556054]
Targeted Disease Basal Cell Carcinoma
Mutation Prevalence 4 out of 30 patients
Mutation Info Missense: W535R
Drugs
Drug Name Vismodegib Drug Info [556054]
Targeted Disease Basal Cell Carcinoma
Mutation Prevalence 4 out of 30 patients
Reference
Ref 555729Smoothened mutation confers resistance to a Hedgehog pathway inhibitor in medulloblastoma. Science. 2009 Oct 23;326(5952):572-4. doi: 10.1126/science.1179386. Epub 2009 Sep 2.
Ref 555858Hedgehog 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. doi: 10.1073/pnas.1114718109. Epub 2012 May 1.
Ref 556027Acquired 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. doi: 10.1016/j.jaad.2014.08.001. Epub 2014 Sep 4.
Ref 556033Smoothened (SMO) receptor mutations dictate resistance to vismodegib in basal cell carcinoma. Mol Oncol. 2015 Feb;9(2):389-97. doi: 10.1016/j.molonc.2014.09.003. Epub 2014 Sep 26.
Ref 556053Genomic analysis of smoothened inhibitor resistance in basal cell carcinoma. Cancer Cell. 2015 Mar 9;27(3):327-41. doi: 10.1016/j.ccell.2015.02.001.
Ref 556054Smoothened variants explain the majority of drug resistance in basal cell carcinoma. Cancer Cell. 2015 Mar 9;27(3):342-53. doi: 10.1016/j.ccell.2015.02.002.

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