Target Information
Target General Information | Top | |||||
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Target ID |
T15776
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Target Name |
Pyruvate dehydrogenase kinase 1 (PDHK1)
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Synonyms |
Pyruvate dehydrogenase kinase isoform 1; Pyruvate dehydrogenase (acetyl-transferring) kinase isozyme 1, mitochondrial; PDHK1; PDH kinase 1
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Gene Name |
PDK1
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Target Type |
Clinical trial target
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[1] | ||||
Disease | [+] 1 Target-related Diseases | + | ||||
1 | Insulin-resistance syndrome [ICD-11: 5A44] | |||||
Function |
Kinase that plays a key role in regulation of glucose and fatty acid metabolism and homeostasis via phosphorylation of the pyruvate dehydrogenase subunits PDHA1 and PDHA2. This inhibits pyruvate dehydrogenase activity, and thereby regulates metabolite flux through the tricarboxylic acid cycle, down-regulates aerobic respiration and inhibits the formation of acetyl-coenzyme A from pyruvate. Plays an important role in cellular responses to hypoxia and is important for cell proliferation under hypoxia. Protects cells against apoptosis in response to hypoxia and oxidative stress.
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BioChemical Class |
Kinase
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UniProt ID | ||||||
EC Number |
EC 2.7.11.2
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Sequence |
MRLARLLRGAALAGPGPGLRAAGFSRSFSSDSGSSPASERGVPGQVDFYARFSPSPLSMK
QFLDFGSVNACEKTSFMFLRQELPVRLANIMKEISLLPDNLLRTPSVQLVQSWYIQSLQE LLDFKDKSAEDAKAIYDFTDTVIRIRNRHNDVIPTMAQGVIEYKESFGVDPVTSQNVQYF LDRFYMSRISIRMLLNQHSLLFGGKGKGSPSHRKHIGSINPNCNVLEVIKDGYENARRLC DLYYINSPELELEELNAKSPGQPIQVVYVPSHLYHMVFELFKNAMRATMEHHANRGVYPP IQVHVTLGNEDLTVKMSDRGGGVPLRKIDRLFNYMYSTAPRPRVETSRAVPLAGFGYGLP ISRLYAQYFQGDLKLYSLEGYGTDAVIYIKALSTDSIERLPVYNKAAWKHYNTNHEADDW CVPSREPKDMTTFRSA Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
HIT2.0 ID | T41Z8G |
Drugs and Modes of Action | Top | |||||
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Approved Drug(s) | [+] 1 Approved Drugs | + | ||||
1 | Dichloroacetate | Drug Info | Phase 4 | Insulin-resistant disorder | [2] | |
Patented Agent(s) | [+] 98 Patented Agents | + | ||||
1 | 1,2-dihydroindazolo[4,3-bc][1,5]benzoxazepine derivative 1 | Drug Info | Patented | Solid tumour/cancer | [1] | |
2 | Benzimidazole and imidazopyridine derivative 1 | Drug Info | Patented | Solid tumour/cancer | [1] | |
3 | Benzonaphthyridine derivative 1 | Drug Info | Patented | Solid tumour/cancer | [1] | |
4 | Benzonaphthyridine derivative 2 | Drug Info | Patented | Solid tumour/cancer | [1] | |
5 | Bis-indolylmaleimide derivative 1 | Drug Info | Patented | Solid tumour/cancer | [1] | |
6 | Dibenzo [c,f]-[2,7]naphthyridine derivative 1 | Drug Info | Patented | Solid tumour/cancer | [1] | |
7 | Heteroaryl-carboxamide derivative 1 | Drug Info | Patented | Solid tumour/cancer | [1] | |
8 | Heteroaryl-carboxamide derivative 10 | Drug Info | Patented | Solid tumour/cancer | [1] | |
9 | Heteroaryl-carboxamide derivative 2 | Drug Info | Patented | Solid tumour/cancer | [1] | |
10 | Heteroaryl-carboxamide derivative 3 | Drug Info | Patented | Solid tumour/cancer | [1] | |
11 | Heteroaryl-carboxamide derivative 4 | Drug Info | Patented | Solid tumour/cancer | [1] | |
12 | Heteroaryl-carboxamide derivative 5 | Drug Info | Patented | Solid tumour/cancer | [1] | |
13 | Heteroaryl-carboxamide derivative 6 | Drug Info | Patented | Solid tumour/cancer | [1] | |
14 | Heteroaryl-carboxamide derivative 7 | Drug Info | Patented | Solid tumour/cancer | [1] | |
15 | Heteroaryl-carboxamide derivative 8 | Drug Info | Patented | Solid tumour/cancer | [1] | |
16 | Heteroaryl-carboxamide derivative 9 | Drug Info | Patented | Solid tumour/cancer | [1] | |
17 | Heterocyclic derivative 10 | Drug Info | Patented | Solid tumour/cancer | [1] | |
18 | Heterocyclic derivative 11 | Drug Info | Patented | Solid tumour/cancer | [1] | |
19 | Heterocyclic derivative 12 | Drug Info | Patented | Solid tumour/cancer | [1] | |
20 | Heterocyclic derivative 13 | Drug Info | Patented | Solid tumour/cancer | [1] | |
21 | Heterocyclic derivative 14 | Drug Info | Patented | Solid tumour/cancer | [1] | |
22 | Heterocyclic derivative 15 | Drug Info | Patented | Solid tumour/cancer | [1] | |
23 | Heterocyclic derivative 16 | Drug Info | Patented | Solid tumour/cancer | [1] | |
24 | Heterocyclic derivative 17 | Drug Info | Patented | Solid tumour/cancer | [1] | |
25 | Heterocyclic derivative 18 | Drug Info | Patented | Solid tumour/cancer | [1] | |
26 | Heterocyclic derivative 19 | Drug Info | Patented | Solid tumour/cancer | [1] | |
27 | Heterocyclic derivative 4 | Drug Info | Patented | Solid tumour/cancer | [1] | |
28 | Heterocyclic derivative 5 | Drug Info | Patented | Solid tumour/cancer | [1] | |
29 | Heterocyclic derivative 6 | Drug Info | Patented | Solid tumour/cancer | [1] | |
30 | Heterocyclic derivative 7 | Drug Info | Patented | Solid tumour/cancer | [1] | |
31 | Heterocyclic derivative 8 | Drug Info | Patented | Solid tumour/cancer | [1] | |
32 | Heterocyclic derivative 9 | Drug Info | Patented | Solid tumour/cancer | [1] | |
33 | Heterocyclic-carboxamide derivative 1 | Drug Info | Patented | Solid tumour/cancer | [1] | |
34 | Heterocyclic-carboxamide derivative 2 | Drug Info | Patented | Solid tumour/cancer | [1] | |
35 | Imidazo quinoline derivative 1 | Drug Info | Patented | Solid tumour/cancer | [1] | |
36 | Indazole derivative 1 | Drug Info | Patented | Solid tumour/cancer | [1] | |
37 | Indolinone derivative 1 | Drug Info | Patented | Solid tumour/cancer | [1] | |
38 | PMID25684022-Compound-EP20041486488 | Drug Info | Patented | Solid tumour/cancer | [1] | |
39 | PMID25684022-Compound-US20120277229 39(1.1) | Drug Info | Patented | Solid tumour/cancer | [1] | |
40 | PMID25684022-Compound-US20120277229 40(1.2) | Drug Info | Patented | Solid tumour/cancer | [1] | |
41 | PMID25684022-Compound-US20120277229 41(1.3) | Drug Info | Patented | Solid tumour/cancer | [1] | |
42 | PMID25684022-Compound-US20120277229 44(1.4) | Drug Info | Patented | Solid tumour/cancer | [1] | |
43 | PMID25684022-Compound-US20120277229 45(1.5) | Drug Info | Patented | Solid tumour/cancer | [1] | |
44 | PMID25684022-Compound-US20130053382 35(1-11) | Drug Info | Patented | Solid tumour/cancer | [1] | |
45 | PMID25684022-Compound-US20130053382 36(3-5) | Drug Info | Patented | Solid tumour/cancer | [1] | |
46 | PMID25684022-Compound-US20130053382 37(4-6) | Drug Info | Patented | Solid tumour/cancer | [1] | |
47 | PMID25684022-Compound-US20130053382 38(5-7) | Drug Info | Patented | Solid tumour/cancer | [1] | |
48 | PMID25684022-Compound-WO2004087707 | Drug Info | Patented | Solid tumour/cancer | [1] | |
49 | PMID25684022-Compound-WO2006015124 | Drug Info | Patented | Solid tumour/cancer | [1] | |
50 | PMID25684022-Compound-WO2008005457 | Drug Info | Patented | Solid tumour/cancer | [1] | |
51 | PMID25684022-Compound-WO2008079988 | Drug Info | Patented | Solid tumour/cancer | [1] | |
52 | PMID25684022-Compound-WO2008107444 | Drug Info | Patented | Solid tumour/cancer | [1] | |
53 | PMID25684022-Compound-WO2009153313 | Drug Info | Patented | Solid tumour/cancer | [1] | |
54 | PMID25684022-Compound-WO2010127754 | Drug Info | Patented | Solid tumour/cancer | [1] | |
55 | PMID25684022-Compound-WO2011137219 35(1-11) | Drug Info | Patented | Solid tumour/cancer | [1] | |
56 | PMID25684022-Compound-WO2011137219 36(3-5) | Drug Info | Patented | Solid tumour/cancer | [1] | |
57 | PMID25684022-Compound-WO2011137219 37(4-6) | Drug Info | Patented | Solid tumour/cancer | [1] | |
58 | PMID25684022-Compound-WO2011137219 38(5-7) | Drug Info | Patented | Solid tumour/cancer | [1] | |
59 | PMID25684022-Compound-WO2012135799 42(1.4) | Drug Info | Patented | Solid tumour/cancer | [1] | |
60 | PMID25684022-Compound-WO2012135799 43(1.5) | Drug Info | Patented | Solid tumour/cancer | [1] | |
61 | Pyrazole derivative 61 | Drug Info | Patented | Solid tumour/cancer | [1] | |
62 | Pyrazolopyridines and imidazopyridine derivative 1 | Drug Info | Patented | Solid tumour/cancer | [1] | |
63 | Pyridinone carboxamide derivative 1 | Drug Info | Patented | Solid tumour/cancer | [1] | |
64 | Pyrido[4,3-d]pyrimidin-5(6H)-one derivative 1 | Drug Info | Patented | Solid tumour/cancer | [1] | |
65 | Pyrimidine derivative 3 | Drug Info | Patented | Solid tumour/cancer | [1] | |
66 | Pyrimidinone derivative 1 | Drug Info | Patented | Solid tumour/cancer | [1] | |
67 | Thiazole carboxamide derivative 1 | Drug Info | Patented | Solid tumour/cancer | [1] | |
68 | Thiazole carboxamide derivative 10 | Drug Info | Patented | Solid tumour/cancer | [1] | |
69 | Thiazole carboxamide derivative 11 | Drug Info | Patented | Solid tumour/cancer | [1] | |
70 | Thiazole carboxamide derivative 12 | Drug Info | Patented | Solid tumour/cancer | [1] | |
71 | Thiazole carboxamide derivative 13 | Drug Info | Patented | Solid tumour/cancer | [1] | |
72 | Thiazole carboxamide derivative 14 | Drug Info | Patented | Solid tumour/cancer | [1] | |
73 | Thiazole carboxamide derivative 15 | Drug Info | Patented | Solid tumour/cancer | [1] | |
74 | Thiazole carboxamide derivative 16 | Drug Info | Patented | Solid tumour/cancer | [1] | |
75 | Thiazole carboxamide derivative 17 | Drug Info | Patented | Solid tumour/cancer | [1] | |
76 | Thiazole carboxamide derivative 18 | Drug Info | Patented | Solid tumour/cancer | [1] | |
77 | Thiazole carboxamide derivative 19 | Drug Info | Patented | Solid tumour/cancer | [1] | |
78 | Thiazole carboxamide derivative 2 | Drug Info | Patented | Solid tumour/cancer | [1] | |
79 | Thiazole carboxamide derivative 20 | Drug Info | Patented | Solid tumour/cancer | [1] | |
80 | Thiazole carboxamide derivative 21 | Drug Info | Patented | Solid tumour/cancer | [1] | |
81 | Thiazole carboxamide derivative 22 | Drug Info | Patented | Solid tumour/cancer | [1] | |
82 | Thiazole carboxamide derivative 23 | Drug Info | Patented | Solid tumour/cancer | [1] | |
83 | Thiazole carboxamide derivative 24 | Drug Info | Patented | Solid tumour/cancer | [1] | |
84 | Thiazole carboxamide derivative 25 | Drug Info | Patented | Solid tumour/cancer | [1] | |
85 | Thiazole carboxamide derivative 26 | Drug Info | Patented | Solid tumour/cancer | [1] | |
86 | Thiazole carboxamide derivative 27 | Drug Info | Patented | Solid tumour/cancer | [1] | |
87 | Thiazole carboxamide derivative 28 | Drug Info | Patented | Solid tumour/cancer | [1] | |
88 | Thiazole carboxamide derivative 29 | Drug Info | Patented | Solid tumour/cancer | [1] | |
89 | Thiazole carboxamide derivative 3 | Drug Info | Patented | Solid tumour/cancer | [1] | |
90 | Thiazole carboxamide derivative 30 | Drug Info | Patented | Solid tumour/cancer | [1] | |
91 | Thiazole carboxamide derivative 4 | Drug Info | Patented | Solid tumour/cancer | [1] | |
92 | Thiazole carboxamide derivative 5 | Drug Info | Patented | Solid tumour/cancer | [1] | |
93 | Thiazole carboxamide derivative 6 | Drug Info | Patented | Solid tumour/cancer | [1] | |
94 | Thiazole carboxamide derivative 7 | Drug Info | Patented | Solid tumour/cancer | [1] | |
95 | Thiazole carboxamide derivative 8 | Drug Info | Patented | Solid tumour/cancer | [1] | |
96 | Thiazole carboxamide derivative 9 | Drug Info | Patented | Solid tumour/cancer | [1] | |
97 | Thieno[3,2-c]pyridine-7-carboxamide derivative 1 | Drug Info | Patented | Solid tumour/cancer | [1] | |
98 | Thieno[3,2-c]pyridine-7-carboxamide derivative 2 | Drug Info | Patented | Solid tumour/cancer | [1] | |
Mode of Action | [+] 1 Modes of Action | + | ||||
Inhibitor | [+] 99 Inhibitor drugs | + | ||||
1 | Dichloroacetate | Drug Info | [3] | |||
2 | 1,2-dihydroindazolo[4,3-bc][1,5]benzoxazepine derivative 1 | Drug Info | [1] | |||
3 | Benzimidazole and imidazopyridine derivative 1 | Drug Info | [1] | |||
4 | Benzonaphthyridine derivative 1 | Drug Info | [1] | |||
5 | Benzonaphthyridine derivative 2 | Drug Info | [1] | |||
6 | Bis-indolylmaleimide derivative 1 | Drug Info | [1] | |||
7 | Dibenzo [c,f]-[2,7]naphthyridine derivative 1 | Drug Info | [1] | |||
8 | Heteroaryl-carboxamide derivative 1 | Drug Info | [1] | |||
9 | Heteroaryl-carboxamide derivative 10 | Drug Info | [1] | |||
10 | Heteroaryl-carboxamide derivative 2 | Drug Info | [1] | |||
11 | Heteroaryl-carboxamide derivative 3 | Drug Info | [1] | |||
12 | Heteroaryl-carboxamide derivative 4 | Drug Info | [1] | |||
13 | Heteroaryl-carboxamide derivative 5 | Drug Info | [1] | |||
14 | Heteroaryl-carboxamide derivative 6 | Drug Info | [1] | |||
15 | Heteroaryl-carboxamide derivative 7 | Drug Info | [1] | |||
16 | Heteroaryl-carboxamide derivative 8 | Drug Info | [1] | |||
17 | Heteroaryl-carboxamide derivative 9 | Drug Info | [1] | |||
18 | Heterocyclic derivative 10 | Drug Info | [1] | |||
19 | Heterocyclic derivative 11 | Drug Info | [1] | |||
20 | Heterocyclic derivative 12 | Drug Info | [1] | |||
21 | Heterocyclic derivative 13 | Drug Info | [1] | |||
22 | Heterocyclic derivative 14 | Drug Info | [1] | |||
23 | Heterocyclic derivative 15 | Drug Info | [1] | |||
24 | Heterocyclic derivative 16 | Drug Info | [1] | |||
25 | Heterocyclic derivative 17 | Drug Info | [1] | |||
26 | Heterocyclic derivative 18 | Drug Info | [1] | |||
27 | Heterocyclic derivative 19 | Drug Info | [1] | |||
28 | Heterocyclic derivative 4 | Drug Info | [1] | |||
29 | Heterocyclic derivative 5 | Drug Info | [1] | |||
30 | Heterocyclic derivative 6 | Drug Info | [1] | |||
31 | Heterocyclic derivative 7 | Drug Info | [1] | |||
32 | Heterocyclic derivative 8 | Drug Info | [1] | |||
33 | Heterocyclic derivative 9 | Drug Info | [1] | |||
34 | Heterocyclic-carboxamide derivative 1 | Drug Info | [1] | |||
35 | Heterocyclic-carboxamide derivative 2 | Drug Info | [1] | |||
36 | Imidazo quinoline derivative 1 | Drug Info | [1] | |||
37 | Indazole derivative 1 | Drug Info | [1] | |||
38 | Indolinone derivative 1 | Drug Info | [1] | |||
39 | PMID25684022-Compound-EP20041486488 | Drug Info | [1] | |||
40 | PMID25684022-Compound-US20120277229 39(1.1) | Drug Info | [1] | |||
41 | PMID25684022-Compound-US20120277229 40(1.2) | Drug Info | [1] | |||
42 | PMID25684022-Compound-US20120277229 41(1.3) | Drug Info | [1] | |||
43 | PMID25684022-Compound-US20120277229 44(1.4) | Drug Info | [1] | |||
44 | PMID25684022-Compound-US20120277229 45(1.5) | Drug Info | [1] | |||
45 | PMID25684022-Compound-US20130053382 35(1-11) | Drug Info | [1] | |||
46 | PMID25684022-Compound-US20130053382 36(3-5) | Drug Info | [1] | |||
47 | PMID25684022-Compound-US20130053382 37(4-6) | Drug Info | [1] | |||
48 | PMID25684022-Compound-US20130053382 38(5-7) | Drug Info | [1] | |||
49 | PMID25684022-Compound-WO2004087707 | Drug Info | [1] | |||
50 | PMID25684022-Compound-WO2006015124 | Drug Info | [1] | |||
51 | PMID25684022-Compound-WO2008005457 | Drug Info | [1] | |||
52 | PMID25684022-Compound-WO2008079988 | Drug Info | [1] | |||
53 | PMID25684022-Compound-WO2008107444 | Drug Info | [1] | |||
54 | PMID25684022-Compound-WO2009153313 | Drug Info | [1] | |||
55 | PMID25684022-Compound-WO2010127754 | Drug Info | [1] | |||
56 | PMID25684022-Compound-WO2011137219 35(1-11) | Drug Info | [1] | |||
57 | PMID25684022-Compound-WO2011137219 36(3-5) | Drug Info | [1] | |||
58 | PMID25684022-Compound-WO2011137219 37(4-6) | Drug Info | [1] | |||
59 | PMID25684022-Compound-WO2011137219 38(5-7) | Drug Info | [1] | |||
60 | PMID25684022-Compound-WO2012135799 42(1.4) | Drug Info | [1] | |||
61 | PMID25684022-Compound-WO2012135799 43(1.5) | Drug Info | [1] | |||
62 | Pyrazole derivative 61 | Drug Info | [1] | |||
63 | Pyrazolopyridines and imidazopyridine derivative 1 | Drug Info | [1] | |||
64 | Pyridinone carboxamide derivative 1 | Drug Info | [1] | |||
65 | Pyrido[4,3-d]pyrimidin-5(6H)-one derivative 1 | Drug Info | [1] | |||
66 | Pyrimidine derivative 3 | Drug Info | [1] | |||
67 | Pyrimidinone derivative 1 | Drug Info | [1] | |||
68 | Thiazole carboxamide derivative 1 | Drug Info | [1] | |||
69 | Thiazole carboxamide derivative 10 | Drug Info | [1] | |||
70 | Thiazole carboxamide derivative 11 | Drug Info | [1] | |||
71 | Thiazole carboxamide derivative 12 | Drug Info | [1] | |||
72 | Thiazole carboxamide derivative 13 | Drug Info | [1] | |||
73 | Thiazole carboxamide derivative 14 | Drug Info | [1] | |||
74 | Thiazole carboxamide derivative 15 | Drug Info | [1] | |||
75 | Thiazole carboxamide derivative 16 | Drug Info | [1] | |||
76 | Thiazole carboxamide derivative 17 | Drug Info | [1] | |||
77 | Thiazole carboxamide derivative 18 | Drug Info | [1] | |||
78 | Thiazole carboxamide derivative 19 | Drug Info | [1] | |||
79 | Thiazole carboxamide derivative 2 | Drug Info | [1] | |||
80 | Thiazole carboxamide derivative 20 | Drug Info | [1] | |||
81 | Thiazole carboxamide derivative 21 | Drug Info | [1] | |||
82 | Thiazole carboxamide derivative 22 | Drug Info | [1] | |||
83 | Thiazole carboxamide derivative 23 | Drug Info | [1] | |||
84 | Thiazole carboxamide derivative 24 | Drug Info | [1] | |||
85 | Thiazole carboxamide derivative 25 | Drug Info | [1] | |||
86 | Thiazole carboxamide derivative 26 | Drug Info | [1] | |||
87 | Thiazole carboxamide derivative 27 | Drug Info | [1] | |||
88 | Thiazole carboxamide derivative 28 | Drug Info | [1] | |||
89 | Thiazole carboxamide derivative 29 | Drug Info | [1] | |||
90 | Thiazole carboxamide derivative 3 | Drug Info | [1] | |||
91 | Thiazole carboxamide derivative 30 | Drug Info | [1] | |||
92 | Thiazole carboxamide derivative 4 | Drug Info | [1] | |||
93 | Thiazole carboxamide derivative 5 | Drug Info | [1] | |||
94 | Thiazole carboxamide derivative 6 | Drug Info | [1] | |||
95 | Thiazole carboxamide derivative 7 | Drug Info | [1] | |||
96 | Thiazole carboxamide derivative 8 | Drug Info | [1] | |||
97 | Thiazole carboxamide derivative 9 | Drug Info | [1] | |||
98 | Thieno[3,2-c]pyridine-7-carboxamide derivative 1 | Drug Info | [1] | |||
99 | Thieno[3,2-c]pyridine-7-carboxamide derivative 2 | Drug Info | [1] |
Cell-based Target Expression Variations | Top | |||||
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Cell-based Target Expression Variations |
Drug Binding Sites of Target | Top | |||||
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Ligand Name: AZD-7545 | Ligand Info | |||||
Structure Description | Structure of pyruvate dehydrogenase kinase isoform 1 in complex with glucose-lowering drug AZD7545 | PDB:2Q8G | ||||
Method | X-ray diffraction | Resolution | 1.90 Å | Mutation | No | [4] |
PDB Sequence |
GVPGQVDFYA
50 RFSPSPLSMK60 QFLDFGSVNA70 CEKTSFMFLR80 QELPVRLANI90 MKEISLLPDN 100 LLRTPSVQLV110 QSWYIQSLQE120 LLDFKDKSAE130 DAKAIYDFTD140 TVIRIRNRHN 150 DVIPTMAQGV160 IEYKESFDPV172 TSQNVQYFLD182 RFYMSRISIR192 MLLNQHSLLF 202 GKHIGSINPN222 CNVLEVIKDG232 YENARRLCDL242 YYINSPELEL252 EELNAKSPGQ 262 PIQVVYVPSH272 LYHMVFELFK282 NAMRATMEHH292 ANRGVYPPIQ302 VHVTLGNEDL 312 TVKMSDRGGG322 VPLRKIDRLF332 NYMYSTAPRP342 RVETSRAVPL352 AGFGYGLPIS 362 RLYAQYFQGD372 LKLYSLEGYG382 TDAVIYIKAL392 STDSIERLPV402 YNKAAWKHYN 412 TNDDWCVP
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Ligand Name: Dichloroacetic acid | Ligand Info | |||||
Structure Description | Structure of pyruvate dehydrogenase kinase isoform 1 in complex with dichloroacetate (DCA) | PDB:2Q8H | ||||
Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | No | [4] |
PDB Sequence |
GVPGQVDFYA
50 RFSPSPLSMK60 QFLDFGSCEK73 TSFMFLRQEL83 PVRLANIMKE93 ISLLPDNLLR 103 TPSVQLVQSW113 YIQSLQELLD123 FKDKSAEDAK133 AIYDFTDTVI143 RIRNRHNDVI 153 PTMAQGVIEY163 KESFDPVTSQ175 NVQYFLDRFY185 MSRISIRMLL195 NQHSLLFGHI 216 GSINPNCNVL226 EVIKDGYENA236 RRLCDLYYIN246 SPELELEELN256 AKSPGQPIQV 266 VYVPSHLYHM276 VFELFKNAMR286 ATMEHHANRG296 VYPPIQVHVT306 LGNEDLTVKM 316 SDRGGGVPLR326 KIDRLFNYMY336 STAPRPRVET346 SRAVPLAGFG356 YGLPISRLYA 366 QYFQGDLKLY376 SLEGYGTDAV386 IYIKALSTDS396 IERLPVYNKA406 AWKHYNTNAD 418 DWCVP
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Click to View More Binding Site Information of This Target with Different Ligands |
Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Tissue Distribution
Human Pathway Affiliation
Biological Network Descriptors
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There is no similarity protein (E value < 0.005) for this target
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Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
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KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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HIF-1 signaling pathway | hsa04066 | Affiliated Target |
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Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy |
Degree | 4 | Degree centrality | 4.30E-04 | Betweenness centrality | 0.00E+00 |
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Closeness centrality | 1.69E-01 | Radiality | 1.26E+01 | Clustering coefficient | 1.00E+00 |
Neighborhood connectivity | 1.68E+01 | Topological coefficient | 6.20E-01 | Eccentricity | 13 |
Download | Click to Download the Full PPI Network of This Target | ||||
Chemical Structure based Activity Landscape of Target | Top |
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Target Poor or Non Binders | Top | |||||
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Target Poor or Non Binders |
Target Regulators | Top | |||||
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Target-regulating microRNAs | ||||||
Target-interacting Proteins |
Target Affiliated Biological Pathways | Top | |||||
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KEGG Pathway | [+] 3 KEGG Pathways | + | ||||
1 | HIF-1 signaling pathway | |||||
2 | Axon guidance | |||||
3 | Central carbon metabolism in cancer |
References | Top | |||||
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REF 1 | PDK1 disruptors and modulators: a patent review.Expert Opin Ther Pat. 2015 May;25(5):513-37. | |||||
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