General Information of the Protein
Protein ID
PT01093
Protein Name
3-phosphoinositide-dependent protein kinase 1
Gene Name
PDPK1
Secondarily
Gene Name
PDK1
Sequence
MARTTSQLYDAVPIQSSVVLCSCPSPSMVRTQTESSTPPGIPGGSRQGPAMDGTAAEPRPGAGSLQHAQPPPQPRKKRPEDFKFGKILGEGSFSTVVLARELATSREYAIKILEKRHIIKENKVPYVTRERDVMSRLDHPFFVKLYFTFQDDEKLYFGLSYAKNGELLKYIRKIGSFDETCTRFYTAEIVSALEYLHGKGIIHRDLKPENILLNEDMHIQITDFGTAKVLSPESKQARANSFVGTAQYVSPELLTEKSACKSSDLWALGCIIYQLVAGLPPFRAGNEYLIFQKIIKLEYDFPEKFFPKARDLVEKLLVLDATKRLGCEEMEGYGPLKAHPFFESVTWENLHQQTPPKLTAYLPAMSEDDEDCYGNYDNLLSQFGCMQVSSSSSSHSLSASDTGLPQRSGSNIEQYIHDLDSNSFELDLQFSEDEKRLLLEKQAGGNPWHQFVENNLILKMGPVDKRKGLFARRRQLLLTEGPHLYYVDPVNKVLKGEIPWSQELRPEAKNFKTFFVHTPNRTYYLMDPSGNAHKWCRKIQEVWRQRYQSHPDAAVQ
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Organism
Homo sapiens, Human
Protein Classification
Enzyme
>
Kinase
>
Protein Kinase
>
AGC protein kinase group
>
AGC protein kinase PDK1 subfamily
Function
Serine/threonine kinase which acts as a master kinase, phosphorylating and activating a subgroup of the AGC family of protein kinases. Its targets include: protein kinase B (PKB/AKT1, PKB/AKT2, PKB/AKT3), p70 ribosomal protein S6 kinase (RPS6KB1), p90 ribosomal protein S6 kinase (RPS6KA1, RPS6KA2 and RPS6KA3), cyclic AMP-dependent protein kinase (PRKACA), protein kinase C (PRKCD and PRKCZ), serum and glucocorticoid-inducible kinase (SGK1, SGK2 and SGK3), p21-activated kinase-1 (PAK1), protein kinase PKN (PKN1 and PKN2). Plays a central role in the transduction of signals from insulin by providing the activating phosphorylation to PKB/AKT1, thus propagating the signal to downstream targets controlling cell proliferation and survival, as well as glucose and amino acid uptake and storage. Negatively regulates the TGF-beta-induced signaling by: modulating the association of SMAD3 and SMAD7 with TGF-beta receptor, phosphorylating SMAD2, SMAD3, SMAD4 and SMAD7, preventing the nuclear translocation of SMAD3 and SMAD4 and the translocation of SMAD7 from the nucleus to the cytoplasm in response to TGF-beta. Activates PPARG transcriptional activity and promotes adipocyte differentiation. Activates the NF-kappa-B pathway via phosphorylation of IKKB. The tyrosine phosphorylated form is crucial for the regulation of focal adhesions by angiotensin II. Controls proliferation, survival, and growth of developing pancreatic cells. Participates in the regulation of Ca(2+) entry and Ca(2+)-activated K(+) channels of mast cells. Essential for the motility of vascular endothelial cells (ECs) and is involved in the regulation of their chemotaxis. Plays a critical role in cardiac homeostasis by serving as a dual effector for cell survival and beta-adrenergic response. Plays an important role during thymocyte development by regulating the expression of key nutrient receptors on the surface of pre-T cells and mediating Notch-induced cell growth and proliferative responses. Provides negative feedback inhibition to toll-like receptor-mediated NF-kappa-B activation in macrophages. Isoform 3 is catalytically inactive.
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Uniprot ID
Primary ID:
O15530

Secondarily ID:
H0Y4Z0
Q59EH6
Q6FI20
Q8IV52
Q9BRD5
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Ensembl ID
ENSG00000140992
HGNC ID
HGNC:8816
Subcellular Location
Cytoplasm
Nucleus
Cell membrane
Cell junction
Focal adhesion
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: CL000218 , BT-474
Compound ID Compound Name Compound Formula
CP0473312
7-methyl-2-((7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)amino)-9-(tetrahydro-2H-pyran-4-yl)-7,9-dihydro-8H-purin-8-one
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C18H20N8O2
 1
1
IC50 > 8300 nM
   TI
   LI
   LO
   TS
Biochemical Assays
Compound ID Compound Name Compound Formula
CP0281194
N-[(3R,5R)-1-[2-amino-6-(3-amino-1H-indazol-6-yl)pyrimidin-4-yl]-5-methylpiperidin-3-yl]-N,3,3-trimethylbutanamide
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C24H34N8O
 1
1 IC50 = 0.631 nM
CP0035637
1,1-Dimethylethyl{(3R,5R)-1-[2-Amino-6-(3-amino-1H-indazol-6-yl)-4-pyrimidinyl]-5-methyl-3-piperidinyl}methylcarbamate
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C24H34N8O2
 1
1 IC50 = 0.7943 nM
CP0035650
(3S,6R)-1-[6-(3-Amino-1H-indazol-6-yl)-2-(methylamino)-4-pyrimidinyl]-6-methyl-N-phenyl-3-piperidinecarboxamide
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C25H28N8O
 1
1 IC50 = 1.585 nM
CP0170186
(3S,6R)-1-[6-(3-Amino-1H-indazol-6-yl)-2-(methylamino)-4-pyrimidinyl]-N-cyclohexyl-6-methyl-3-piperidinecarboxamide
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C25H34N8O
 2
1 IC50 = 2.5 nM
2 IC50 = 10 nM
CP0164512
(2S,5R)-4-[6-(3-Amino-1H-indazol-6-yl)-2-(methylamino)-4-pyrimidinyl]-5-ethyl-N-phenyl-2-morpholinecarboxamide
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C25H28N8O2
 1
1 IC50 = 3.162 nM
CP0222470
(3S,6R)-1-[2-Amino-6-(3-amino-1H-indazol-6-yl)-4-pyrimidinyl]-6-methyl-N-phenyl-3-piperidinecarboxamide
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C24H26N8O
 1
1 IC50 = 3.162 nM
CP0290173
(2S,5R)-4-[6-(3-amino-1H-indazol-6-yl)-2-(methylamino)-4-pyrimidinyl]-N-cyclohexyl-5-methyl-2-morpholinecarboxamide
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C24H32N8O2
 1
1 IC50 = 3.162 nM
CP0158682
US8664236, A16
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C23H21ClN8O
 1
1 IC50 = 4.7 nM
CP0119426
US8664236, A23
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C24H21ClN8O2
 1
1 IC50 = 4.8 nM
CP0039182
BX-517
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C15H14N4O2
 3
1 IC50 = 5 nM
2 IC50 = 6 nM
3 IC50 = 9 nM
CP0314834
US8664236, A26
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C23H21FN8O
 1
1 IC50 = 5 nM
CP0318508
US8664236, A27
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C23H20N8O
 1
1 IC50 = 5 nM
CP0035658
(2S,5R)-4-[2-Amino-6-(3-amino-1H-indazol-6-yl)-4-pyrimidinyl]-5-methyl-N-phenyl-2-morpholinecarboxamide
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C23H24N8O2
 1
1 IC50 = 5.012 nM
CP0035635
(2S,5R)-4-[6-(3-Amino-1H-indazol-6-yl)-2-(methylamino)-4-pyrimidinyl]-N-cyclohexyl-5-ethyl-2-morpholinecarboxamide
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C25H34N8O2
 1
1 IC50 = 6.31 nM
CP0207434
1,1-Dimethylethyl{(3R,5R)-1-[2-amino-6-(3-amino-1H-indazol-6-yl)-4-pyrimidinyl]-5-methyl-3-piperidinyl}carbamate
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C22H30N8O2
 1
1 IC50 = 6.31 nM
CP0172227
US8664236, A25
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C23H20F2N8O
 1
1 IC50 = 6.5 nM
CP0438242
US8664236, A29
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C24H23ClN8O
 1
1 IC50 = 7 nM
CP0174340
US8664236, A10
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C22H19ClN8
 1
1 IC50 = 7.6 nM
CP0074211
US8664236, A30
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C24H21N9
 1
1 IC50 = 7.9 nM
CP0217037
(3S,6R)-1-[2-Amino-6-(3-amino-1H-indazol-6-yl)-4-pyrimidinyl]-N-cyclohexyl-6-methyl-3-piperidinecarboxamide
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C24H32N8O
 1
1 IC50 = 7.943 nM
CP0577898
US8664236, A31
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C24H25N9
 1
1 IC50 = 8.7 nM
CP0074210
US8664236, A9
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C22H19FN8
 1
1 IC50 = 9.7 nM
CP0216812
US8664236, A21
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C25H26N8O2
 1
1 IC50 = 11 nM
CP0174341
US8664236, A12
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C23H22N8
 1
1 IC50 = 12 nM
CP0136907
US8664236, A4
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C23H22N8O
 1
1 IC50 = 13 nM
CP0074981
4-ethyl-6-[5-(1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]pyrimidin-2-amine
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C16H15N7
 1
1 IC50 = 13 nM
CP0268213
US8664236, A11
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C22H20N8
 1
1 IC50 = 16.5 nM
CP0313350
US8664236, A15
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C25H25ClN8O
 1
1 IC50 = 17 nM
CP0313374
US8664236, A35
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C24H23N9O
 1
1 IC50 = 17 nM
CP0039185
BX-201
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C14H12N4O2
 1
1 IC50 = 18 nM
CP0325023
US8664236, A43
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C26H27N9O
 1
1 IC50 = 22 nM
CP0062687
US8664236, A5
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C25H26N8O3
 1
1 IC50 = 24 nM
CP0247613
N-[3-[[5-bromo-4-[3-(thiophene-2-carbonylamino)propylamino]pyrimidin-2-yl]amino]phenyl]pyrrolidine-1-carboxamide
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C23H26BrN7O2S
 1
1 IC50 = 26 nM
CP0158683
US8664236, A19
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C24H23ClN8
 1
1 IC50 = 30 nM
CP0220217
US8664236, A1
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C22H19FN8
 1
1 IC50 = 34 nM
CP0438243
US8664236, A42
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C24H20FN7
 1
1 IC50 = 45.5 nM
CP0246240
US8664236, A13
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C23H21ClN8
 1
1 IC50 = 46 nM
CP0074209
US8664236, A8
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C22H19ClN8
 1
1 IC50 = 51 nM
CP0158681
US8664236, A14
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C24H24N8
 1
1 IC50 = 51 nM
CP0906206
US9238651, A55
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C25H25N7O
 1
1 IC50 = 54 nM
CP0023790
4-ethyl-6-[5-(1-piperidin-4-ylpyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]pyrimidin-2-amine
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C21H24N8
 1
1 IC50 = 58 nM
CP0331584
US8664236, A3
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C24H21N7
 1
1 IC50 = 59.5 nM
CP0026424
15,16-dimethoxy-6-methyl-8,12-diazatetracyclo[8.8.0.0^{2,7}.0^{13,18}]octadeca-1(10),2(7),3,5,8,11,13,15,17-nonaene-5,9-diamine
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C19H18N4O2
 1
1 IC50 = 60 nM
CP0074208
US8664236, A2
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C24H23N7
 1
1 IC50 = 65 nM
CP0342881
US9238651, A24
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C25H23ClN8O
 1
1 IC50 = 69 nM
CP0069210
US8569511, 1
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C22H20F2N6O2
 2
1 IC50 = 80 nM
2 IC50 = 143 nM
CP0197716
4-[5-[1-[2-(dimethylamino)ethyl]pyrazol-4-yl]-1H-pyrrolo[2,3-b]pyridin-3-yl]-6-ethylpyrimidin-2-amine
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C20H24N8
 1
1 IC50 = 82 nM
CP0031346
4-butyl-6-[5-(1-piperidin-4-ylpyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]pyrimidin-2-amine
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C23H28N8
 1
1 IC50 = 84 nM
CP0191538
4-ethyl-6-[5-(1-methylpyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]pyrimidin-2-amine
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C17H17N7
 1
1 IC50 = 85 nM
CP0563778
US8664236, A28
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C27H28FN9O
 1
1 IC50 = 89 nM
CP0300378
US8664236, A22
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C25H23N9O2
 1
1 IC50 = 90 nM
CP0112599
US8569511, 2
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C23H22F2N6O2
 3
1 IC50 = 90 nM
2 IC50 = 94 nM
3 IC50 = 159 nM
CP0133052
4-ethyl-6-[5-[1-(2-methylpropyl)pyrazol-4-yl]-1H-pyrrolo[2,3-b]pyridin-3-yl]pyrimidin-2-amine
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C20H23N7
 1
1 IC50 = 110 nM
CP0191537
4-ethyl-6-[5-(furan-2-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]pyrimidin-2-amine
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C17H15N5O
 1
1 IC50 = 120 nM
CP0361572
US8664236, A6
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C26H25N7
 1
1 IC50 = 130 nM
CP0158684
US8664236, A20
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C19H18N10S
 1
1 IC50 = 155 nM
CP0132928
4-[5-(6-aminopyridin-3-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-6-ethylpyrimidin-2-amine
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C18H17N7
 1
1 IC50 = 170 nM
CP0272839
US8664236, A30a
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C22H18FN7
 1
1 IC50 = 190 nM
CP0366688
(1R)-N-methyl-2,3-dihydro-1H-inden-1-amine
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C10H13N
 1
1 IC50 = 200 nM
CP0244029
US8664236, A17
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C23H19FN8
 1
1 IC50 = 200 nM
CP0112814
4-ethyl-6-[5-(1H-pyrazol-5-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]pyrimidin-2-amine
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C16H15N7
 1
1 IC50 = 260 nM
CP0240521
4-(3-aminopropyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-2-amine
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C14H16N6
 1
1 IC50 = 390 nM
CP0356163
4-ethyl-6-(5-pyridin-4-yl-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-2-amine
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C18H16N6
 1
1 IC50 = 450 nM
CP0132921
4-(5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-6-ethylpyrimidin-2-amine
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C13H12BrN5
 1
1 IC50 = 480 nM
CP0132922
4-ethyl-6-(5-pyridin-3-yl-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-2-amine
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C18H16N6
 1
1 IC50 = 500 nM
CP0562367
US8664236, A7
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C26H24ClN7
 1
1 IC50 = 870 nM
CP0191454
4-(4-aminobutyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-2-amine
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C15H18N6
 1
1 IC50 = 1000 nM
CP0023612
4-butyl-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-2-amine
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C15H17N5
 1
1 IC50 = 1100 nM
CP0191535
4-ethyl-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-2-amine
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C13H13N5
 1
1 IC50 = 1200 nM
CP0273443
(3R,6S)-1-(2-amino-6-(3-amino-1H-indazol-6-yl)pyrimidin-4-yl)-6-methyl-N-phenylpiperidine-3-carboxamide
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C24H26N8O
 1
1 IC50 = 1258.93 nM
CP0283467
4-propyl-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-2-amine
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C14H15N5
 1
1 IC50 = 1800 nM
CP0544740
4-pentyl-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-2-amine
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C16H19N5
 1
1 IC50 = 2200 nM
CP0132924
4-ethyl-6-[5-(2-methylpyrazol-3-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]pyrimidin-2-amine
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C17H17N7
 1
1 IC50 = 2400 nM
CP0112815
4-ethyl-6-[5-(1,3,5-trimethylpyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]pyrimidin-2-amine
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C19H21N7
 1
1 IC50 = 2700 nM
CP0534254
4-ethyl-6-(5-phenyl-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-2-amine
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C19H17N5
 1
1 IC50 = 3500 nM
CP0314833
US8664236, A18
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C25H23FN8
 1
1 IC50 = 5900 nM
CP0004541
MERIOLIN 1
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C11H9N5
 1
1 IC50 = 5900 nM
CP0011191
4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzene-1-sulfonamide
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C17H14F3N3O2S
 1
1 IC50 = 48000 nM
CP0132920
3-(6-ethylpyrimidin-4-yl)-1H-pyrrolo[2,3-b]pyridine
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C13H12N4
 1
1 IC50 > 10000 nM
CP0019876
(2R,3R)-3-[[6-(4-amino-7-propan-2-ylpyrrolo[2,3-d]pyrimidine-5-carbonyl)pyrazin-2-yl]amino]-2-(4-fluorophenyl)pyrrolidine-1-carbaldehyde
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C25H25FN8O2
 1
1 Ki = 0.7 nM
CP0017416
1-[(2R,3R)-3-[[6-(4-amino-7-propan-2-ylpyrrolo[2,3-d]pyrimidine-5-carbonyl)pyrazin-2-yl]amino]-2-(4-fluorophenyl)pyrrolidin-1-yl]ethanone
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C26H27FN8O2
 1
1 Ki = 1.4 nM
CP0017417
1-[(2R,3R)-3-[[6-(4-amino-7-propan-2-ylpyrrolo[2,3-d]pyrimidine-5-carbonyl)pyrazin-2-yl]amino]-2-phenylpyrrolidin-1-yl]ethanone
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C26H28N8O2
 1
1 Ki = 1.4 nM
Clinical Information about the Protein
Target 1 ( Phosphoinositide dependent protein kinase-1 (PDPK1) )
Target Type Clinical trial Target
Disease 2 Target-related Diseases  2
1 Lymphoma [ICD-11: 2A80-2A86]
2 Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Clinical Trial Drug(s) 1 Clinical Trial Drug  1
1 AR-12 Phase 1
Lymphoma
Investigative Drug(s) 1 Investigative Drug  1
1 GSK-2334470 Investigative
Solid tumour/cancer
Target 2 ( PDK-1 messenger RNA (PDK-1 mRNA) )
Target Type Literature-reported Target