Details of the Drug Therapeutic Target (DTT)

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

DTT Name PDK-1 messenger RNA (PDK-1 mRNA)
Synonyms PDK1 (mRNA); HPDK1 (mRNA); 3-phosphoinositide-dependent protein kinase 1 (mRNA); 3-Phosphoinositide-dependent kinase-1 (mRNA); 3'-phosphoinositide dependent kinase 1 (mRNA)
Gene Name PDPK1
DTT Type
Literature-reported target
 [1]
BioChemical Class
mRNA target
UniProt ID
PDPK1_HUMAN
TTD ID
T08074
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
EC 2.7.11.1
Sequence
MARTTSQLYDAVPIQSSVVLCSCPSPSMVRTQTESSTPPGIPGGSRQGPAMDGTAAEPRP
GAGSLQHAQPPPQPRKKRPEDFKFGKILGEGSFSTVVLARELATSREYAIKILEKRHIIK
ENKVPYVTRERDVMSRLDHPFFVKLYFTFQDDEKLYFGLSYAKNGELLKYIRKIGSFDET
CTRFYTAEIVSALEYLHGKGIIHRDLKPENILLNEDMHIQITDFGTAKVLSPESKQARAN
SFVGTAQYVSPELLTEKSACKSSDLWALGCIIYQLVAGLPPFRAGNEYLIFQKIIKLEYD
FPEKFFPKARDLVEKLLVLDATKRLGCEEMEGYGPLKAHPFFESVTWENLHQQTPPKLTA
YLPAMSEDDEDCYGNYDNLLSQFGCMQVSSSSSSHSLSASDTGLPQRSGSNIEQYIHDLD
SNSFELDLQFSEDEKRLLLEKQAGGNPWHQFVENNLILKMGPVDKRKGLFARRRQLLLTE
GPHLYYVDPVNKVLKGEIPWSQELRPEAKNFKTFFVHTPNRTYYLMDPSGNAHKWCRKIQ
EVWRQRYQSHPDAAVQ
Function
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. Serine/threonine kinase which acts as a master kinase, phosphorylating and activating a subgroup of the AGC family of protein kinases.
KEGG Pathway
PPAR signaling pathway (hsa03320 )
FoxO signaling pathway (hsa04068 )
Sphingolipid signaling pathway (hsa04071 )
mTOR signaling pathway (hsa04150 )
PI3K-Akt signaling pathway (hsa04151 )
AMPK signaling pathway (hsa04152 )
Focal adhesion (hsa04510 )
T cell receptor signaling pathway (hsa04660 )
Fc epsilon RI signaling pathway (hsa04664 )
Neurotrophin signaling pathway (hsa04722 )
Insulin signaling pathway (hsa04910 )
Thyroid hormone signaling pathway (hsa04919 )
Aldosterone-regulated sodium reabsorption (hsa04960 )
Toxoplasmosis (hsa05145 )
Hepatitis C (hsa05160 )
Proteoglycans in cancer (hsa05205 )
Endometrial cancer (hsa05213 )
Prostate cancer (hsa05215 )
Non-small cell lung cancer (hsa05223 )
Choline metabolism in cancer (hsa05231 )
Reactome Pathway
PIP3 activates AKT signaling (R-HSA-1257604 )
Activation of AKT2 (R-HSA-165158 )
Role of LAT2/NTAL/LAB on calcium mobilization (R-HSA-2730905 )
FCERI mediated NF-kB activation (R-HSA-2871837 )
Integrin alphaIIb beta3 signaling (R-HSA-354192 )
CD28 dependent PI3K/Akt signaling (R-HSA-389357 )
CTLA4 inhibitory signaling (R-HSA-389513 )
G beta (R-HSA-392451 )
VEGFR2 mediated vascular permeability (R-HSA-5218920 )
VEGFR2 mediated cell proliferation (R-HSA-5218921 )
CLEC7A (Dectin-1) signaling (R-HSA-5607764 )
RHO GTPases activate PKNs (R-HSA-5625740 )
Constitutive Signaling by AKT1 E17K in Cancer (R-HSA-5674400 )
GPVI-mediated activation cascade (R-HSA-114604 )

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DTT
26 Investigative Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
(Z)-3-((1H-pyrrol-2-yl)methylene)indolin-2-one DM27WDP Discovery agent N.A. Investigative [2]
BX-201 DMGK7U5 Discovery agent N.A. Investigative [2]
BX-517 DMBQIEF Discovery agent N.A. Investigative [2]
ISIS 29219 DM37R5F Discovery agent N.A. Investigative [3]
ISIS 29223 DMMQPFE Discovery agent N.A. Investigative [3]
ISIS 29224 DM9UNWE Discovery agent N.A. Investigative [3]
ISIS 29232 DMLES7J Discovery agent N.A. Investigative [3]
ISIS 29233 DMGV4O7 Discovery agent N.A. Investigative [3]
ISIS 29234 DM1XAPO Discovery agent N.A. Investigative [3]
ISIS 29236 DMAXD7P Discovery agent N.A. Investigative [3]
ISIS 29237 DMPYJEB Discovery agent N.A. Investigative [3]
ISIS 29239 DMHQF1J Discovery agent N.A. Investigative [3]
ISIS 29243 DMZ7UM2 Discovery agent N.A. Investigative [3]
ISIS 29244 DMTHVEL Discovery agent N.A. Investigative [3]
ISIS 29246 DM0DG1K Discovery agent N.A. Investigative [3]
ISIS 29255 DMK2QPU Discovery agent N.A. Investigative [3]
ISIS 29256 DMF1MJ2 Discovery agent N.A. Investigative [3]
ISIS 29257 DMUM2H1 Discovery agent N.A. Investigative [3]
ISIS 29469 DMVCFQ5 Discovery agent N.A. Investigative [3]
ISIS 29470 DMPCK7Y Discovery agent N.A. Investigative [3]
ISIS 29471 DMG4RMZ Discovery agent N.A. Investigative [3]
ISIS 29475 DMEBQUN Discovery agent N.A. Investigative [3]
ISIS 29477 DMKQMXV Discovery agent N.A. Investigative [3]
MiR-375 DM4P9LJ Discovery agent N.A. Investigative [1]
NU-6102 DMMOFKD Discovery agent N.A. Investigative [4]
SU-6689 DMDNA23 Discovery agent N.A. Investigative [2]
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⏷ Show the Full List of 26 Investigative Drug(s)

References

1 miR-375 targets 3'-phosphoinositide-dependent protein kinase-1 and regulates glucose-induced biological responses in pancreatic beta-cells. Diabetes. 2008 Oct;57(10):2708-17.
2 Indolinone based phosphoinositide-dependent kinase-1 (PDK1) inhibitors. Part 1: design, synthesis and biological activity. Bioorg Med Chem Lett. 2007 Jul 15;17(14):3814-8.
3 US patent application no. 6,124,272, Antisense modulation of PDK-1 expression.
4 Triazolo[1,5-a]pyrimidines as novel CDK2 inhibitors: protein structure-guided design and SAR. Bioorg Med Chem Lett. 2006 Mar 1;16(5):1353-7.