Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT8J1S3)

DTT Name Smoothened homolog (SMO)
Synonyms Smo-D473H; SMOH; Protein Gx
Gene Name SMO
DTT Type
Successful target
 [1]
BioChemical Class
GPCR frizzled
UniProt ID
SMO_HUMAN
TTD ID
T66505
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MAAARPARGPELPLLGLLLLLLLGDPGRGAASSGNATGPGPRSAGGSARRSAAVTGPPPP
LSHCGRAAPCEPLRYNVCLGSVLPYGATSTLLAGDSDSQEEAHGKLVLWSGLRNAPRCWA
VIQPLLCAVYMPKCENDRVELPSRTLCQATRGPCAIVERERGWPDFLRCTPDRFPEGCTN
EVQNIKFNSSGQCEVPLVRTDNPKSWYEDVEGCGIQCQNPLFTEAEHQDMHSYIAAFGAV
TGLCTLFTLATFVADWRNSNRYPAVILFYVNACFFVGSIGWLAQFMDGARREIVCRADGT
MRLGEPTSNETLSCVIIFVIVYYALMAGVVWFVVLTYAWHTSFKALGTTYQPLSGKTSYF
HLLTWSLPFVLTVAILAVAQVDGDSVSGICFVGYKNYRYRAGFVLAPIGLVLIVGGYFLI
RGVMTLFSIKSNHPGLLSEKAASKINETMLRLGIFGFLAFGFVLITFSCHFYDFFNQAEW
ERSFRDYVLCQANVTIGLPTKQPIPDCEIKNRPSLLVEKINLFAMFGTGIAMSTWVWTKA
TLLIWRRTWCRLTGQSDDEPKRIKKSKMIAKAFSKRHELLQNPGQELSFSMHTVSHDGPV
AGLAFDLNEPSADVSSAWAQHVTKMVARRGAILPQDISVTPVATPVPPEEQANLWLVEAE
ISPELQKRLGRKKKRRKRKKEVCPLAPPPELHPPAPAPSTIPRLPQLPRQKCLVAAGAWG
AGDSCRQGAWTLVSNPFCPEPSPPQDPFLPSAPAPVAWAHGRRQGLGPIHSRTNLMDTEL
MDADSDF
Function
Binding of sonic hedgehog (SHH) to its receptor patched is thought to prevent normal inhibition by patched of smoothened (SMO). Required for the accumulation of KIF7, GLI2 and GLI3 in the cilia. Interacts with DLG5 at the ciliary base to induce the accumulation of KIF7 and GLI2 at the ciliary tip for GLI2 activation. G protein-coupled receptor that probably associates with the patched protein (PTCH) to transduce the hedgehog's proteins signal.
KEGG Pathway
Hedgehog signaling pathway (hsa04340 )
Pathways in cancer (hsa05200 )
Proteoglycans in cancer (hsa05205 )
Basal cell carcinoma (hsa05217 )
Reactome Pathway
Hedgehog 'off' state (R-HSA-5610787 )
Activation of SMO (R-HSA-5635838 )
Class B/2 (Secretin family receptors) (R-HSA-373080 )

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DTT
2 Approved Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
PF-04449913 DMSB068 Chronic myelomonocytic leukaemia 2A40 Approved [2]
Vismodegib DM5IXKQ Basal cell carcinoma 2C32 Approved [1]
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5 Clinical Trial Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
LDE225 DMM9F25 Basal cell carcinoma 2C32 Phase 2 [3]
LY2940680 DMTJWIQ Solid tumour/cancer 2A00-2F9Z Phase 1/2 [2]
BMS-833923 DM459Q7 Solid tumour/cancer 2A00-2F9Z Phase 1b [4]
LEQ-506 DM5INZP Solid tumour/cancer 2A00-2F9Z Phase 1 [5]
TAK-441 DM7DFBL Solid tumour/cancer 2A00-2F9Z Phase 1 [6]
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75 Patented Agent(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Bicyclic hexapeptide derivative 1 DMWTCM8 N. A. N. A. Patented [7]
Bicyclic hexapeptide derivative 2 DMJP1IK N. A. N. A. Patented [7]
Cyclic sulfonamide derivative 1 DMJMWDV N. A. N. A. Patented [7]
Cyclic sulfonamide derivative 2 DMXSZ5B N. A. N. A. Patented [7]
Cyclic sulfonamide derivative 3 DMBANT7 N. A. N. A. Patented [7]
Cyclic sulfonamide derivative 4 DMWAU49 N. A. N. A. Patented [7]
Imidazo bicyclic iminium derivative 3 DMENYZ0 N. A. N. A. Patented [7]
Imidazo bicyclic iminium derivative 4 DMHRV8J N. A. N. A. Patented [7]
Imidazo bicyclic iminium derivative 5 DMS8GIU N. A. N. A. Patented [7]
Imidazo bicyclic iminium derivative 6 DMEP5MJ N. A. N. A. Patented [7]
Imidazo bicyclic iminium derivative 7 DM0Y4X8 N. A. N. A. Patented [7]
Imidazo bicyclic iminium derivative 8 DMBMFPC N. A. N. A. Patented [7]
Imidazo bicyclic iminium derivative 9 DMQXCT1 N. A. N. A. Patented [7]
Isoflavone derivative 1 DMMCWH9 N. A. N. A. Patented [8]
Isoflavone derivative 2 DMTWAH3 N. A. N. A. Patented [8]
Isoflavone derivative 3 DMYFKR2 N. A. N. A. Patented [8]
Isoflavone derivative 4 DMYRU7I N. A. N. A. Patented [8]
Isoflavone derivative 5 DM2GL47 N. A. N. A. Patented [8]
Isoflavone derivative 6 DM2ZYVL N. A. N. A. Patented [8]
Isoflavone derivative 7 DMNCHBL N. A. N. A. Patented [8]
Isoflavone derivative 8 DMN0XJQ N. A. N. A. Patented [8]
Isoflavone derivative 9 DMA78MD N. A. N. A. Patented [8]
PMID25726713-Compound-10 DMZ73D9 N. A. N. A. Patented [7]
PMID25726713-Compound-11 DMN42OT N. A. N. A. Patented [7]
PMID25726713-Compound-12 DMD3AHN N. A. N. A. Patented [7]
PMID25726713-Compound-13 DM8LZ60 N. A. N. A. Patented [7]
PMID25726713-Compound-14 DM6ORB9 N. A. N. A. Patented [7]
PMID25726713-Compound-15 DM67WM4 N. A. N. A. Patented [7]
PMID25726713-Compound-16 DM3BOZP N. A. N. A. Patented [7]
PMID25726713-Compound-17 DM9MFUN N. A. N. A. Patented [7]
PMID25726713-Compound-18 DMP7C5L N. A. N. A. Patented [7]
PMID25726713-Compound-19 DMQJZLI N. A. N. A. Patented [7]
PMID25726713-Compound-20 DMZOG9S N. A. N. A. Patented [7]
PMID25726713-Compound-21 DMB0DS5 N. A. N. A. Patented [7]
PMID25726713-Compound-22 DMJUHXB N. A. N. A. Patented [7]
PMID25726713-Compound-23 DMEXNOP N. A. N. A. Patented [7]
PMID25726713-Compound-24 DMMFK2Q N. A. N. A. Patented [7]
PMID25726713-Compound-25 DMLCPWT N. A. N. A. Patented [7]
PMID25726713-Compound-26 DMJ8MXZ N. A. N. A. Patented [7]
PMID25726713-Compound-27 DMTL73W N. A. N. A. Patented [7]
PMID25726713-Compound-28 DMYM60P N. A. N. A. Patented [7]
PMID25726713-Compound-29 DM3QU80 N. A. N. A. Patented [7]
PMID25726713-Compound-30 DMFBHAC N. A. N. A. Patented [7]
PMID25726713-Compound-31 DMN13BI N. A. N. A. Patented [7]
PMID25726713-Compound-32 DMIFH8T N. A. N. A. Patented [7]
PMID25726713-Compound-33 DMEQ9BN N. A. N. A. Patented [7]
PMID25726713-Compound-34 DMCXDKS N. A. N. A. Patented [7]
PMID25726713-Compound-35 DMYCABN N. A. N. A. Patented [7]
PMID25726713-Compound-36 DMYPT63 N. A. N. A. Patented [7]
PMID25726713-Compound-37 DMGXOJK N. A. N. A. Patented [7]
PMID25726713-Compound-38 DM4XJST N. A. N. A. Patented [7]
PMID25726713-Compound-39 DMVL25C N. A. N. A. Patented [7]
PMID25726713-Compound-42 DM5E2B3 N. A. N. A. Patented [7]
PMID25726713-Compound-43 DME9QCM N. A. N. A. Patented [7]
PMID25726713-Compound-44 DMEFA20 N. A. N. A. Patented [7]
PMID25726713-Compound-45 DMR8OVI N. A. N. A. Patented [7]
PMID25726713-Compound-46 DM27DQP N. A. N. A. Patented [7]
PMID25726713-Compound-47 DMXE5KM N. A. N. A. Patented [7]
PMID25726713-Compound-48 DMSIOUA N. A. N. A. Patented [7]
PMID25726713-Compound-49 DM2CT4G N. A. N. A. Patented [7]
PMID25726713-Compound-50 DM3BDFV N. A. N. A. Patented [7]
PMID25726713-Compound-51 DMF0OW4 N. A. N. A. Patented [7]
PMID25726713-Compound-56 DMUHEP8 N. A. N. A. Patented [7]
PMID25726713-Compound-57 DMMZHB1 N. A. N. A. Patented [7]
PMID25726713-Compound-58 DMPDX3L N. A. N. A. Patented [7]
PMID25726713-Compound-59 DMBF1OG N. A. N. A. Patented [7]
PMID25726713-Compound-60 DMR8HSU N. A. N. A. Patented [7]
PMID25726713-Compound-61 DMYXK7I N. A. N. A. Patented [7]
PMID25726713-Compound-62 DMXNLTR N. A. N. A. Patented [7]
PMID25726713-Compound-63 DMT0QLO N. A. N. A. Patented [7]
PMID25726713-Compound-64 DM6A8TS N. A. N. A. Patented [7]
Pyrimidine derivative 19 DMLPO0K N. A. N. A. Patented [7]
Pyrimidine derivative 20 DMQUEDK N. A. N. A. Patented [7]
Pyrimidine derivative 21 DMELA2F N. A. N. A. Patented [7]
Pyrimidine derivative 22 DMN64AK N. A. N. A. Patented [7]
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⏷ Show the Full List of 75 Patented Agent(s)
4 Investigative Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
1-Benzyl-4-(4-phenylpiperazin-1-yl)phthalazine DM4NGUL Discovery agent N.A. Investigative [9]
AZD8542 DM0HTXO Discovery agent N.A. Investigative [10]
CYCLOPAMINE DMEM2SW Discovery agent N.A. Investigative [11]
SMOi2-17 DMABIX1 Solid tumour/cancer 2A00-2F9Z Investigative [10]
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Molecular Expression Atlas (MEA) of This DTT

Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This DTT
Disease Name ICD 11 Studied Tissue p-value Fold-Change Z-score
Skin cancer 2C82 Skin 4.01E-06 -0.18 -0.35
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References

1 Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
2 Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
3 Inhibition of Hedgehog signalling by NVP-LDE225 (Erismodegib) interferes with growth and invasion of human renal cell carcinoma cells. Br J Cancer. 2014 Sep 9;111(6):1168-79.
4 Clinical pipeline report, company report or official report of Exelixis (2011).
5 Discovery of NVP-LEQ506, a second-generation inhibitor of smoothened. ChemMedChem. 2013 Aug;8(8):1261-5.
6 TAK-441, a novel investigational smoothened antagonist, delays castration-resistant progression in prostate cancer by disrupting paracrine hedgehog signaling. Int J Cancer. 2013 Oct 15;133(8):1955-66.
7 Hedgehog inhibitors: a patent review (2013 - present).Expert Opin Ther Pat. 2015 May;25(5):549-65.
8 Evaluation of WO2014207069 A1: Multitarget Hedgehog pathway inhibitors and uses thereof.Expert Opin Ther Pat. 2016;26(4):529-35.
9 1-amino-4-benzylphthalazines as orally bioavailable smoothened antagonists with antitumor activity. J Med Chem. 2009 Jul 9;52(13):3954-68.
10 URL: 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. (Target id: 239).
11 Identification and structure-activity relationships of ortho-biphenyl carboxamides as potent Smoothened antagonists inhibiting the Hedgehog signali... Bioorg Med Chem Lett. 2009 Jan 15;19(2):328-31.