General Information of the Protein
Protein ID
PT04361
Protein Name
Protein smoothened
Secondarily
Protein Name
Protein Gx
Gene Name
SMO
Secondarily
Gene Name
SMOH
Sequence
MAAARPARGPELPLLGLLLLLLLGDPGRGAASSGNATGPGPRSAGGSARRSAAVTGPPPPLSHCGRAAPCEPLRYNVCLGSVLPYGATSTLLAGDSDSQEEAHGKLVLWSGLRNAPRCWAVIQPLLCAVYMPKCENDRVELPSRTLCQATRGPCAIVERERGWPDFLRCTPDRFPEGCTNEVQNIKFNSSGQCEVPLVRTDNPKSWYEDVEGCGIQCQNPLFTEAEHQDMHSYIAAFGAVTGLCTLFTLATFVADWRNSNRYPAVILFYVNACFFVGSIGWLAQFMDGARREIVCRADGTMRLGEPTSNETLSCVIIFVIVYYALMAGVVWFVVLTYAWHTSFKALGTTYQPLSGKTSYFHLLTWSLPFVLTVAILAVAQVDGDSVSGICFVGYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKSNHPGLLSEKAASKINETMLRLGIFGFLAFGFVLITFSCHFYDFFNQAEWERSFRDYVLCQANVTIGLPTKQPIPDCEIKNRPSLLVEKINLFAMFGTGIAMSTWVWTKATLLIWRRTWCRLTGQSDDEPKRIKKSKMIAKAFSKRHELLQNPGQELSFSMHTVSHDGPVAGLAFDLNEPSADVSSAWAQHVTKMVARRGAILPQDISVTPVATPVPPEEQANLWLVEAEISPELQKRLGRKKKRRKRKKEVCPLAPPPELHPPAPAPSTIPRLPQLPRQKCLVAAGAWGAGDSCRQGAWTLVSNPFCPEPSPPQDPFLPSAPAPVAWAHGRRQGLGPIHSRTNLMDTELMDADSDF
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Organism
Homo sapiens, Human
Protein Classification
Membrane receptor
>
Frizzled family G protein-coupled receptor
>
Smoothened receptor (frizzled family GPCR)
Function
G protein-coupled receptor which associates with the patched protein (PTCH) to transduce hedgehog protein signaling. Binding of sonic hedgehog (SHH) to its receptor patched prevents inhibition of smoothened (SMO) by patched. When active, SMO binds to and sequesters protein kinase A catalytic subunit PRKACA at the cell membrane, preventing PRKACA-mediated phosphorylation of GLI transcription factors which releases the GLI proteins from PRKACA-mediated inhibition and allows for transcriptional activation of hedgehog pathway target genes (By similarity). Required for the accumulation of KIF7, GLI2 and GLI3 in the cilia (PubMed:19592253). Interacts with DLG5 at the ciliary base to induce the accumulation of KIF7 and GLI2 at the ciliary tip for GLI2 activation (By similarity).
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Uniprot ID
Primary ID:
Q99835

Secondarily ID:
A4D1K5
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Ensembl ID
ENSG00000128602
HGNC ID
HGNC:11119
Subcellular Location
Cell membrane
Cell projection
Cilium
Map of Molecular Bioactivity Related to the Protein
Map of Molecular Bioactivity Related to the Protein

Protein
Cell Line
Compound

Bioactivity Value:

<= 0.1 μM
> 0.1 μM and <= 10 μM
> 10 μM
Imprecise Activity
Table of Molecular Bioactivities Related to the Protein
Cell Line ID: CL000026 , CHO-K1
Compound ID Compound Name Compound Formula
CP0472123
2-{6-[4-(4-Benzylphthalazin-1-yl)piperazin-1-yl]pyridin-3-yl}propan-2-ol
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C27H29N5O
 1
1
IC50 = 8 nM
   TI
   LI
   LO
   TS
CP0455389
1-{6-[4-(4-Benzylphthalazin-1-yl)piperazin-1-yl]pyridin-3-yl}1-methylethylamine
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C27H30N6
 1
1
IC50 = 15 nM
   TI
   LI
   LO
   TS
CP0455398
6-[(S)-4-(4-Benzylphthalazin-1-yl)-3-methylpiperazin-1-yl]nicotinonitrile
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C26H24N6
 1
1
IC50 = 17 nM
   TI
   LI
   LO
   TS
CP0497372
1-{6-[4-(4-Benzylphthalazin-1-yl)piperazin-1-yl]pyridin-3-yl}cyclopropanol
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C27H27N5O
 1
1
IC50 = 21 nM
   TI
   LI
   LO
   TS
CP0502393
6-{4-[4-(4-Chlorobenzyl)phthalazin-1-yl]piperazin-1-yl}nicotinonitrile
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C25H21ClN6
 1
1
IC50 = 25 nM
   TI
   LI
   LO
   TS
CP0457490
6-{4-[4-(4-Cyanobenzyl)phthalazin-1-yl]piperazin-1-yl}nicotinonitrile
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C26H21N7
 1
1
IC50 = 34 nM
   TI
   LI
   LO
   TS
CP0498345
6-[(R)-4-(4-Benzylphthalazin-1-yl)-2-methylpiperazin-1-yl]nicotinonitrile
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C26H24N6
 1
1
IC50 = 34 nM
   TI
   LI
   LO
   TS
CP0422210
6-[(S)-4-(4-Benzylphthalazin-1-yl)-2-methylpiperazin-1-yl]nicotinonitrile
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C26H24N6
 1
1
IC50 = 59 nM
   TI
   LI
   LO
   TS
CP0397016
1-{6-[4-(4-Benzylphthalazin-1-yl)piperazin-1-yl]pyridin-3-yl}ethanol
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C26H27N5O
 1
1
IC50 = 67 nM
   TI
   LI
   LO
   TS
CP0452552
(+/-)-2-{6-[4-(4-Benzylphthalazin-1-yl)piperazin-1-yl]pyridin-3-yl}propane-1,2-diol
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C27H29N5O2
 1
1
IC50 = 70 nM
   TI
   LI
   LO
   TS
CP0452558
6-{4-[4-(3-Chlorobenzyl)phthalazin-1-yl]piperazin-1-yl}nicotinonitrile
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C25H21ClN6
 1
1
IC50 = 82 nM
   TI
   LI
   LO
   TS
CP0387836
1-Benzyl-4-[4-(5-trifluoromethylpyridin-2-yl)piperazin-1-yl]phthalazine
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C25H22F3N5
 1
1
IC50 = 95 nM
   TI
   LI
   LO
   TS
CP0422211
6-{4-[4-(4-Fluorobenzyl)phthalazin-1-yl]piperazin-1-yl}nicotinonitrile
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C25H21FN6
 1
1
IC50 = 103 nM
   TI
   LI
   LO
   TS
CP0457488
6-[4-(4-Benzylphthalazin-1-yl)piperazin-1-yl]nicotinonitrile
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C25H22N6
 1
1
IC50 = 112 nM
   TI
   LI
   LO
   TS
CP0374377
6-{4-[4-(4-Trifluoromethylbenzyl)phthalazin-1-yl]piperazin-1-yl}nicotinonitrile
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C26H21F3N6
 1
1
IC50 = 185 nM
   TI
   LI
   LO
   TS
CP0452554
N-[[6-[4-(4-benzylphthalazin-1-yl)piperazin-1-yl]pyridin-3-yl]methyl]acetamide
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C27H28N6O
 1
1
IC50 = 196 nM
   TI
   LI
   LO
   TS
CP0387837
6-[(R)-4-(4-Benzylphthalazin-1-yl)-3-methylpiperazin-1-yl]nicotinonitrile
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C26H24N6
 1
1
IC50 = 217 nM
   TI
   LI
   LO
   TS
CP0374376
7-Benzyl-4-[4-(5-trifluoromethylpyridin-2-yl)piperazin-1-yl]furo[2,3-d]pyridazine
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C23H20F3N5O
 1
1
IC50 = 230 nM
   TI
   LI
   LO
   TS
CP0457489
6-[4-(4-Benzylphthalazin-1-yl)piperazin-1-yl]pyridine-3-sulfonicAcid Amide
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C24H24N6O2S
 1
1
IC50 = 306 nM
   TI
   LI
   LO
   TS
CP0474046
6-[4-(4-Benzylphthalazin-1-yl)[1,4]diazepan-1-yl]nicotinonitrile
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C26H24N6
 1
1
IC50 = 391 nM
   TI
   LI
   LO
   TS
CP0498346
4-(1-Benzyl-1H-indol-3-yl)-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-5'-carbonitrile
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C26H24N4
 1
1
IC50 = 401 nM
   TI
   LI
   LO
   TS
CP0457491
[6-[4-(4-benzylphthalazin-1-yl)piperazin-1-yl]pyridin-3-yl]methanol
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C25H25N5O
 1
1
IC50 = 484 nM
   TI
   LI
   LO
   TS
CP0374378
1-[6-[4-(4-benzylphthalazin-1-yl)piperazin-1-yl]pyridin-3-yl]-N,N-dimethylmethanamine
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C27H30N6
 1
1
IC50 = 654 nM
   TI
   LI
   LO
   TS
CP0497373
6-[4-(4-Benzylphthalazin-1-yl)piperazin-1-yl]nicotinamide
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C25H24N6O
 1
1
IC50 = 724 nM
   TI
   LI
   LO
   TS
CP0452555
1-Benzyl-4-(4-pyridin-2-yl-piperazin-1-yl)phthalazine
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C24H23N5
 1
1
IC50 = 1243 nM
   TI
   LI
   LO
   TS
CP0387803
6-[4-(4-Benzylphthalazin-1-yl)piperazin-1-yl]nicotinic Acid
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C25H23N5O2
 1
1
IC50 = 2261 nM
   TI
   LI
   LO
   TS
CP0407677
4-{4-[4-(5-Cyanopyridin-2-yl)piperazin-1-yl]phthalazin-1-ylmethyl}benzoic Acid Methyl Ester
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C27H24N6O2
 1
1
IC50 = 2929 nM
   TI
   LI
   LO
   TS
CP0428583
1-Benzyl-4-(4-phenylpiperazin-1-yl)phthalazine
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C25H24N4
 1
1
IC50 = 4237 nM
   TI
   LI
   LO
   TS
CP0387801
4-Benzyl-7-[4-(5-trifluoromethylpyridin-2-yl)piperazin-1-yl]furo[2,3-d]pyridazine
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C23H20F3N5O
 1
1
IC50 > 5000 nM
   TI
   LI
   LO
   TS
CP0387805
4-{4-[4-(5-Cyanopyridin-2-yl)piperazin-1-yl]phthalazin-1-ylmethyl}benzoic Acid
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C26H22N6O2
 1
1
IC50 > 5000 nM
   TI
   LI
   LO
   TS
CP0397036
4-[1-(4-Benzylphthalazin-1-yl)piperidin-4-yl]benzonitrile
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C27H24N4
 1
1
IC50 > 5000 nM
   TI
   LI
   LO
   TS
CP0397039
7-Benzyl-4-[4-(5-trifluoromethylpyridin-2-yl)piperazin-1-yl]-1Himidazo[4,5-d]pyridazine
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C22H20F3N7
 1
1
IC50 > 5000 nM
   TI
   LI
   LO
   TS
CP0428584
1-Pyridin-4-ylmethyl-4-(4-pyridin-2-ylpiperazin-1-yl)phthalazine
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C23H22N6
 1
1
IC50 > 5000 nM
   TI
   LI
   LO
   TS
CP0431427
6-[4-(4-Benzylisoquinolin-1-yl)piperazin-1-yl]nicotinonitrile
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C26H23N5
 1
1
IC50 > 5000 nM
   TI
   LI
   LO
   TS
CP0455276
6-[4-(1-Benzylisoquinolin-4-yl)piperazin-1-yl]nicotinonitrile
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C26H23N5
 1
1
IC50 > 5000 nM
   TI
   LI
   LO
   TS
Biochemical Assays
Compound ID Compound Name Compound Formula
CP0068085
2-chloro-N-(4-chloro-3-(pyridin-2-yl)phenyl)-4-(methylsulfonyl)benzamide
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C19H14Cl2N2O3S
 3
1 EC50 = 2 nM
2 IC50 = 20 nM
3 Kd = 97.5 nM
CP0326988
LEQ-506
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C25H32N6O
 1
1 IC50 < 100 nM
Clinical Information about the Protein
Target 1 ( Smoothened homolog (SMO) )
Target Type Successful Target
Disease 4 Target-related Diseases  4
1 Chronic myelomonocytic leukaemia [ICD-11: 2A40]
2 Basal cell carcinoma [ICD-11: 2C32]
3 Skin cancer [ICD-11: 2C30-2C37]
4 Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Approved Drug(s) 2 Approved Drugs  2
1 PF-04449913 Approved
Chronic myelomonocytic leukaemia
2 Vismodegib Approved
Basal cell carcinoma
Clinical Trial Drug(s) 4 Clinical Trial Drugs  4
1 LDE225 Phase 2
Skin cancer
2 LY2940680 Phase 1/2
Solid tumour/cancer
3 LEQ-506 Phase 1
Solid tumour/cancer
4 TAK-441 Phase 1
Solid tumour/cancer
Target 2 ( Smoothened D473H mutant (SMO D473H) )
Target Type Patented-recorded Target
Similar Protein(s) and Bioactivity Statistics
90% Identity
Protein ID Protein Name Protein Organism
PT02397 Protein smoothened Mus musculus, Mouse