Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTSN6QU)

DTT Name HIF1-alpha messenger RNA (HIF1A mRNA)
Synonyms
bHLHe78 (mRNA); Transcription factor HIF-1 (mRNA); PASD8 (mRNA); PAS domain-containing protein 8 (mRNA); Member of PAS protein 1 (mRNA); MOP1 (mRNA); Hypoxia-inducible transcription factor (HIF)-1 (mRNA); Hypoxia-inducible factor 1-alpha (mRNA); Hypoxia-inducible factor 1 (mRNA); Hypoxia inducible factor 1 (mRNA); HIF1-alpha (mRNA); HIF1 alpha (mRNA); HIF-1alpha (mRNA); HIF-1-alpha (mRNA); HIF-1 alpha (mRNA); Class E basic helix-loop-helix protein 78 (mRNA); Basic-helix-loop-helix-PAS protein MOP1 (mRNA); ARNT-interacting protein (mRNA); ARNT interacting protein (mRNA)
Gene Name HIF1A
DTT Type
Clinical trial target
 [1]
BioChemical Class
mRNA target
UniProt ID
HIF1A_HUMAN
TTD ID
T51748
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MEGAGGANDKKKISSERRKEKSRDAARSRRSKESEVFYELAHQLPLPHNVSSHLDKASVM
RLTISYLRVRKLLDAGDLDIEDDMKAQMNCFYLKALDGFVMVLTDDGDMIYISDNVNKYM
GLTQFELTGHSVFDFTHPCDHEEMREMLTHRNGLVKKGKEQNTQRSFFLRMKCTLTSRGR
TMNIKSATWKVLHCTGHIHVYDTNSNQPQCGYKKPPMTCLVLICEPIPHPSNIEIPLDSK
TFLSRHSLDMKFSYCDERITELMGYEPEELLGRSIYEYYHALDSDHLTKTHHDMFTKGQV
TTGQYRMLAKRGGYVWVETQATVIYNTKNSQPQCIVCVNYVVSGIIQHDLIFSLQQTECV
LKPVESSDMKMTQLFTKVESEDTSSLFDKLKKEPDALTLLAPAAGDTIISLDFGSNDTET
DDQQLEEVPLYNDVMLPSPNEKLQNINLAMSPLPTAETPKPLRSSADPALNQEVALKLEP
NPESLELSFTMPQIQDQTPSPSDGSTRQSSPEPNSPSEYCFYVDSDMVNEFKLELVEKLF
AEDTEAKNPFSTQDTDLDLEMLAPYIPMDDDFQLRSFDQLSPLESSSASPESASPQSTVT
VFQQTQIQEPTANATTTTATTDELKTVTKDRMEDIKILIASPSPTHIHKETTSATSSPYR
DTQSRTASPNRAGKGVIEQTEKSHPRSPNVLSVALSQRTTVPEEELNPKILALQNAQRKR
KMEHDGSLFQAVGIGTLLQQPDDHAATTSLSWKRVKGCKSSEQNGMEQKTIILIPSDLAC
RLLGQSMDESGLPQLTSYDCEVNAPIQGSRNLLQGEELLRALDQVN
Function
Under hypoxic conditions, activates the transcription of over 40 genes, including erythropoietin, glucose transporters, glycolytic enzymes, vascular endothelial growth factor, HILPDA, and other genes whose protein products increase oxygen delivery or facilitate metabolic adaptation to hypoxia. Plays an essential role in embryonic vascularization, tumor angiogenesis and pathophysiology of ischemic disease. Heterodimerizes with ARNT; heterodimer binds to core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters. Activation requires recruitment of transcriptional coactivators such as CREBBP and EP300. Activity is enhanced by interaction with both, NCOA1 or NCOA2. Interaction with redox regulatory protein APEX seems to activate CTAD and potentiates activation by NCOA1 and CREBBP. Involved in the axonal distribution and transport of mitochondria in neurons during hypoxia. Functions as a master transcriptional regulator of the adaptive response to hypoxia.
KEGG Pathway
HIF-1 signaling pathway (hsa04066 )
mTOR signaling pathway (hsa04150 )
Thyroid hormone signaling pathway (hsa04919 )
Pathways in cancer (hsa05200 )
Proteoglycans in cancer (hsa05205 )
Renal cell carcinoma (hsa05211 )
Central carbon metabolism in cancer (hsa05230 )
Choline metabolism in cancer (hsa05231 )
Reactome Pathway
Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha (R-HSA-1234176 )
BMAL1 (R-HSA-1368108 )
NOTCH1 Intracellular Domain Regulates Transcription (R-HSA-2122947 )
Circadian Clock (R-HSA-400253 )
Regulation of gene expression by Hypoxia-inducible Factor (R-HSA-1234158 )

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DTT
1 Clinical Trial Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
PT2385 DMCSN69 Recurrent glioblastoma 2A00.00 Phase 2 [1]
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13 Investigative Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
(5-(1-benzyl-1H-indazol-3-yl)furan-2-yl)methanol DM15P2G Discovery agent N.A. Investigative [2]
ISIS 175510 DMPAXR4 Discovery agent N.A. Investigative [3]
ISIS 298697 DM0WH1L Discovery agent N.A. Investigative [3]
ISIS 298699 DMB28JW Discovery agent N.A. Investigative [3]
ISIS 298700 DM3DE98 Discovery agent N.A. Investigative [3]
ISIS 298701 DMVIXND Discovery agent N.A. Investigative [3]
ISIS 298702 DM4L7NE Discovery agent N.A. Investigative [3]
ISIS 298711 DMCDWSG Discovery agent N.A. Investigative [3]
ISIS 298712 DMGJ4AO Discovery agent N.A. Investigative [3]
ISIS 298743 DMD3NSQ Discovery agent N.A. Investigative [3]
ISIS 298744 DM8VMQ4 Discovery agent N.A. Investigative [3]
ISIS 298745 DM9YMPI Discovery agent N.A. Investigative [3]
ISIS 298746 DMHOJ0Z Discovery agent N.A. Investigative [3]
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⏷ Show the Full List of 13 Investigative Drug(s)

References

1 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
2 Synthesis of (aryloxyacetylamino)-isonicotinic/nicotinic acid analogues as potent hypoxia-inducible factor (HIF)-1alpha inhibitors. Bioorg Med Chem Lett. 2007 Nov 15;17(22):6305-10.
3 US patent application no. 7,217,572, Modulation of HIF1.alpha. and HIF2.alpha. expression.