General Information of the Protein
Protein ID
PT02791
Protein Name
Hypoxia-inducible factor 1-alpha
Secondarily
Protein Name
ARNT-interacting protein
Basic-helix-loop-helix-PAS protein MOP1
Class E basic helix-loop-helix protein 78
Member of PAS protein 1
PAS domain-containing protein 8
Gene Name
HIF1A
Secondarily
Gene Name
BHLHE78
MOP1
PASD8
Sequence
MEGAGGANDKKKISSERRKEKSRDAARSRRSKESEVFYELAHQLPLPHNVSSHLDKASVMRLTISYLRVRKLLDAGDLDIEDDMKAQMNCFYLKALDGFVMVLTDDGDMIYISDNVNKYMGLTQFELTGHSVFDFTHPCDHEEMREMLTHRNGLVKKGKEQNTQRSFFLRMKCTLTSRGRTMNIKSATWKVLHCTGHIHVYDTNSNQPQCGYKKPPMTCLVLICEPIPHPSNIEIPLDSKTFLSRHSLDMKFSYCDERITELMGYEPEELLGRSIYEYYHALDSDHLTKTHHDMFTKGQVTTGQYRMLAKRGGYVWVETQATVIYNTKNSQPQCIVCVNYVVSGIIQHDLIFSLQQTECVLKPVESSDMKMTQLFTKVESEDTSSLFDKLKKEPDALTLLAPAAGDTIISLDFGSNDTETDDQQLEEVPLYNDVMLPSPNEKLQNINLAMSPLPTAETPKPLRSSADPALNQEVALKLEPNPESLELSFTMPQIQDQTPSPSDGSTRQSSPEPNSPSEYCFYVDSDMVNEFKLELVEKLFAEDTEAKNPFSTQDTDLDLEMLAPYIPMDDDFQLRSFDQLSPLESSSASPESASPQSTVTVFQQTQIQEPTANATTTTATTDELKTVTKDRMEDIKILIASPSPTHIHKETTSATSSPYRDTQSRTASPNRAGKGVIEQTEKSHPRSPNVLSVALSQRTTVPEEELNPKILALQNAQRKRKMEHDGSLFQAVGIGTLLQQPDDHAATTSLSWKRVKGCKSSEQNGMEQKTIILIPSDLACRLLGQSMDESGLPQLTSYDCEVNAPIQGSRNLLQGEELLRALDQVN
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Organism
Homo sapiens, Human
Protein Classification
Transcription factor
Function
Functions as a master transcriptional regulator of the adaptive response to hypoxia (PubMed:11292861, PubMed:11566883, PubMed:15465032, PubMed:16973622, PubMed:17610843, PubMed:18658046, PubMed:20624928, PubMed:22009797, PubMed:9887100, PubMed:30125331). 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 (PubMed:11292861, PubMed:11566883, PubMed:15465032, PubMed:16973622, PubMed:17610843, PubMed:20624928, PubMed:22009797, PubMed:9887100, PubMed:30125331). Plays an essential role in embryonic vascularization, tumor angiogenesis and pathophysiology of ischemic disease (PubMed:22009797). Heterodimerizes with ARNT; heterodimer binds to core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters (By similarity). Activation requires recruitment of transcriptional coactivators such as CREBBP and EP300 (PubMed:9887100, PubMed:16543236). Activity is enhanced by interaction with NCOA1 and/or NCOA2 (PubMed:10594042). Interaction with redox regulatory protein APEX1 seems to activate CTAD and potentiates activation by NCOA1 and CREBBP (PubMed:10202154, PubMed:10594042). Involved in the axonal distribution and transport of mitochondria in neurons during hypoxia (PubMed:19528298).
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Uniprot ID
Primary ID:
Q16665

Secondarily ID:
C0LZJ3
Q53XP6
Q96PT9
Q9UPB1
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Ensembl ID
ENSG00000100644
HGNC ID
HGNC:4910
Subcellular Location
Cytoplasm
Nucleus
Nucleus speckle
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: CL000275 , AGS
Compound ID Compound Name Compound Formula
CP0378883
3-[2-(4-adamantan-1-yl-phenoxy)-acetylamino]-benzoic acid
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C25H27NO4
 1
1
IC50 = 350 nM
   TI
   LI
   LO
   TS
CP0499642
3-[2-(4-adamantan-1-yl-phenoxy)-acetylamino]-benzoic acid methyl ester
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C26H29NO4
 1
1
IC50 = 700 nM
   TI
   LI
   LO
   TS
CP0490586
2-[2-(4-adamantan-1-yl-phenoxy)-acetylamino]-isonicotinic acid
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C24H26N2O4
 1
1
IC50 = 800 nM
   TI
   LI
   LO
   TS
CP0449106
5-[2-(4-adamantan-1-yl-phenoxy)-acetylamino]-nicotinamide
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C24H27N3O3
 1
1
IC50 = 900 nM
   TI
   LI
   LO
   TS
CP0457924
5-[2-(4-adamantan-1-yl-phenoxy)-acetylamino]-N-(2-pyridin-4-yl-ethyl)-nicotinamide
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C31H34N4O3
 1
1
IC50 = 1300 nM
   TI
   LI
   LO
   TS
CP0393031
2-[2-(4-adamantan-1-yl-phenoxy)-acetylamino]-isonicotinamide
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C24H27N3O3
 1
1
IC50 = 1800 nM
   TI
   LI
   LO
   TS
CP0016093
(5-(1-benzyl-1H-indazol-3-yl)furan-2-yl)methanol
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C19H16N2O2
 1
1
IC50 = 2000 nM
   TI
   LI
   LO
   TS
CP0454169
2-[2-(4-adamantan-1-yl-phenoxy)-acetylamino]-isonicotinic acid methyl ester
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C25H28N2O4
 1
1
IC50 = 2000 nM
   TI
   LI
   LO
   TS
CP0454171
5-[2-(4-adamantan-1-yl-phenoxy)-acetylamino]-nicotinic acid methyl ester
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C25H28N2O4
 1
1
IC50 = 5000 nM
   TI
   LI
   LO
   TS
CP0434361
2-[2-(4-adamantan-1-yl-phenoxy)-acetylamino]-N-(2-pyridin-4-yl-ethyl)-isonicotinamide
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C31H34N4O3
 1
1
IC50 = 5200 nM
   TI
   LI
   LO
   TS
CP0440841
5-[2-(4-adamantan-1-yl-phenoxy)-acetylamino]-N-(3-imidazol-1-yl-propyl)-nicotinamide
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C30H35N5O3
 1
1
IC50 > 10000 nM
   TI
   LI
   LO
   TS
CP0442349
2-[2-(4-adamantan-1-yl-phenoxy)-acetylamino]-N-(3-imidazol-1-yl-propyl)-isonicotinamide
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C30H35N5O3
 1
1
IC50 = 11000 nM
   TI
   LI
   LO
   TS
CP0399590
2-[2-(4-adamantan-1-yl-phenoxy)-acetylamino]-N-(4-chloro-phenyl)-isonicotinamide
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C30H30ClN3O3
 1
1
IC50 = 18600 nM
   TI
   LI
   LO
   TS
CP0454170
5-[2-(4-adamantan-1-yl-phenoxy)-acetylamino]-nicotinic acid
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C24H26N2O4
 1
1
IC50 > 30000 nM
   TI
   LI
   LO
   TS
CP0454275
5-[2-(4-adamantan-1-yl-phenoxy)-acetylamino]-N-furan-2-ylmethyl-nicotinamide
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C29H31N3O4
 1
1
IC50 = 30000 nM
   TI
   LI
   LO
   TS
CP0464172
2-[2-(4-adamantan-1-yl-phenoxy)-acetylamino]-N-furan-2-ylmethyl-isonicotinamide
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C29H31N3O4
 1
1
IC50 > 30000 nM
   TI
   LI
   LO
   TS
Biochemical Assays
Compound ID Compound Name Compound Formula
CP0025202
(1S,3R,11R,14S)-14-(hydroxymethyl)-3-[(1S,3R,11R,14S)-14-(hydroxymethyl)-18-methyl-13,17-dioxo-15,16-dithia-10,12,18-triazapentacyclo[12.2.2.01,12.03,11.04,9]octadeca-4,6,8-trien-3-yl]-18-methyl-15,16-dithia-10,12,18-triazapentacyclo[12.2.2.01,12.03,11.04,9]octadeca-4,6,8-triene-13,17-dione
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C30H28N6O6S4
 1
1 IC50 = 12500 nM
Clinical Information about the Protein
Target 1 ( HIF1-alpha messenger RNA (HIF1A mRNA) )
Target Type Clinical trial Target
Disease 1 Target-related Disease  1
1 Recurrent glioblastoma [ICD-11: 2A00.00]
Clinical Trial Drug(s) 1 Clinical Trial Drug  1
1 PT2385 Phase 2
Recurrent glioblastoma
Target 2 ( Hypoxia-inducible factor 1 alpha (HIF-1A) )
Target Type Clinical trial Target
Disease 3 Target-related Diseases  3
1 Lymphoma [ICD-11: 2A80-2A86]
2 Pulmonary arterial hypertension [ICD-11: BB01.0]
3 Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Approved Drug(s) 1 Approved Drug  1
1 HIF-1alpha Phase 4
Lymphoma
Clinical Trial Drug(s) 2 Clinical Trial Drugs  2
1 2-Methoxyestradiol Phase 2
Pulmonary arterial hypertension
2 PX-478 Phase 1
Solid tumour/cancer