| 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 |
|---|
| Mutation Info |
Missense: A459V |
| Drugs |
| Drug Name |
Vismodegib |
Drug Info |
[1]
|
| Targeted Disease |
Basal Cell Carcinoma |
| Mutation Prevalence |
3 out of 12 patients |
|
| Mutation Info |
Missense: C469Y |
| Drugs |
| Drug Name |
Vismodegib |
Drug Info |
[1]
|
| 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 |
Basal Cell Carcinoma |
| Mutation Prevalence |
6 out of 14 patients |
|
| Mutation Info |
Missense: D473H |
| Drugs |
| Drug Name |
Saridegib |
Drug Info |
[4]
|
| Targeted Disease |
Cancer |
|
| Drug Name |
Gdc-0449 |
Drug Info |
[5]
|
| Targeted Disease |
Primitive Neuroectodermal Tumour Medulloblastoma |
|
| Mutation Info |
Missense: D473N |
| Drugs |
| 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 |
Basal Cell Carcinoma |
|
| Mutation Info |
Missense: F460L |
| Drugs |
| 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 |
Basal Cell Carcinoma |
|
| Mutation Info |
Missense: H231R |
| Drugs |
| 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 |
Basal Cell Carcinoma |
|
| Mutation Info |
Missense: Q477E |
| Drugs |
| 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 |
Basal Cell Carcinoma |
|
| Mutation Info |
Missense: T241M |
| Drugs |
| Drug Name |
Vismodegib |
Drug Info |
[1]
|
| 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 |
Basal Cell Carcinoma |
| Mutation Prevalence |
1 out of 30 patients |
|
| Mutation Info |
Missense: V321M |
| Drugs |
| Drug Name |
Vismodegib |
Drug Info |
[6],
[1]
|
| 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 |
Basal Cell Carcinoma |
| Mutation Prevalence |
2 out of 30 patients |
|
| Mutation Info |
Missense: W281L |
| Drugs |
| Drug Name |
Vismodegib |
Drug Info |
[6]
|
| Targeted Disease |
Basal Cell Carcinoma |
|
| Mutation Info |
Missense: W535L |
| Drugs |
| 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 |
Basal Cell Carcinoma |
| Mutation Prevalence |
4 out of 30 patients |
|
| Reference |
|---|
| REF 1 | Genomic 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 2 | Smoothened (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 3 | Smoothened 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. |
|---|
| REF 4 | 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. doi: 10.1073/pnas.1114718109. Epub 2012 May 1. |
|---|
| REF 5 | Smoothened 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 6 | 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. doi: 10.1016/j.jaad.2014.08.001. Epub 2014 Sep 4. |
|---|
