Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTA6ZN2)

• DTT Name: Nuclear factor erythroid 2-related factor 2 (Nrf2)
• Synonyms: Nuclear factor, erythroid derived 2, like 2; NRF2; NFE2-related factor 2; NF-E2-related factor 2; HEBP1
• Gene Name: NFE2L2
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Basic leucine zipper bZIP
• UniProt ID: NF2L2_HUMAN
• TTD ID: T88505
• Sequence:
  MMDLELPPPGLPSQQDMDLIDILWRQDIDLGVSREVFDFSQRRKEYELEKQKKLEKERQE
  QLQKEQEKAFFAQLQLDEETGEFLPIQPAQHIQSETSGSANYSQVAHIPKSDALYFDDCM
  QLLAQTFPFVDDNEVSSATFQSLVPDIPGHIESPVFIATNQAQSPETSVAQVAPVDLDGM
  QQDIEQVWEELLSIPELQCLNIENDKLVETTMVPSPEAKLTEVDNYHFYSSIPSMEKEVG
  NCSPHFLNAFEDSFSSILSTEDPNQLTVNSLNSDATVNTDFGDEFYSAFIAEPSISNSMP
  SPATLSHSLSELLNGPIDVSDLSLCKAFNQNHPESTAEFNDSDSGISLNTSPSVASPEHS
  VESSSYGDTLLGLSDSEVEELDSAPGSVKQNGPKTPVHSSGDMVQPLSPSQGQSTHVHDA
  QCENTPEKELPVSPGHRKTPFTKDKHSSRLEAHLTRDELRAKALHIPFPVEKIINLPVVD
  FNEMMSKEQFNEAQLALIRDIRRRGKNKVAAQNCRKRKLENIVELEQDLDHLKDEKEKLL
  KEKGENDKSLHLLKKQLSTLYLEVFSMLRDEDGKPYSPSEYSLQQTRDGNVFLVPKSKKP
  DVKKN
• Function: Important for the coordinated up-regulation of genes in response to oxidative stress and the regulation of cellular redox conditions. May be involved in the transcriptional activation of genes of the beta-globin cluster by mediating enhancer activity of hypersensitive site 2 of the beta-globin locus control region. Transcription activator that binds to antioxidant response (ARE) elements in the promoter regions of target genes.
• KEGG Pathway: Protein processing in endoplasmic reticulum (hsa04141)
• Reactome Pathway:
  Potential therapeutics for SARS (R-HSA-9679191)
  Regulation of HMOX1 expression and activity (R-HSA-9707587)
  Heme signaling (R-HSA-9707616)
  KEAP1-NFE2L2 pathway (R-HSA-9755511)
  Nuclear events mediated by NFE2L2 (R-HSA-9759194)
  GSK3B and BTRC (R-HSA-9762114)
  Neddylation (R-HSA-8951664)

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Omaveloxolone	DMLMNFX	Friedreich's ataxia	8A03.10	Approved	[2]

6 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ABT-RTA-408	DM9Y1XB	Non-small-cell lung cancer	2C25.Y	Phase 2	[1]
CXA10	DMM7Z6K	Focal segmental glomerulosclerosis	MF8Y	Phase 2	[3]
OT-551	DMTNOXQ	Ocular inflammation	9C61.24	Phase 2	[4]
OT551	DMHKIOF	Age-related macular degeneration	9B75.0	Phase 2	[5]
SFX-01	DMAQW9M	Breast cancer	2C60-2C65	Phase 2	[6]
HPP971	DMZXG7Q	Non-alcoholic steatohepatitis	DB92.1	Phase 1	[7]

62 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
1,2,3,4-tetrahydroisoquinoline derivative 1	DMW5DC1	N. A.	N. A.	Patented	[8]
1-phenyl-1,3,4-triazole derivative 1	DMS5EHL	N. A.	N. A.	Patented	[8]
1-phenyl-1,3,4-triazole derivative 2	DMO7310	N. A.	N. A.	Patented	[8]
1-phenyl-1,3,4-triazole derivative 3	DMU8FC1	N. A.	N. A.	Patented	[8]
2-hydroxybenzamide derivative 1	DMER2ZQ	N. A.	N. A.	Patented	[8]
2-hydroxybenzamide derivative 2	DM9FRN6	N. A.	N. A.	Patented	[8]
3-phenyl propanoic derivative 1	DMW86YI	N. A.	N. A.	Patented	[8]
3-phenyl propanoic derivative 2	DM17D30	N. A.	N. A.	Patented	[8]
3-phenyl propanoic derivative 3	DM5GKS6	N. A.	N. A.	Patented	[8]
4-(2-cyclohexylethoxy) aniline derivative 1	DME30O6	N. A.	N. A.	Patented	[8]
4-(2-cyclohexylethoxy) aniline derivative 2	DM8F4QP	N. A.	N. A.	Patented	[8]
4-(2-cyclohexylethoxy) aniline derivative 3	DMJU0SO	N. A.	N. A.	Patented	[8]
4-(2-cyclohexylethoxy) aniline derivative 4	DMPULIC	N. A.	N. A.	Patented	[8]
Benzamide derivative 5	DM6W0TM	N. A.	N. A.	Patented	[8]
Benzamide derivative 6	DM80TDC	N. A.	N. A.	Patented	[8]
Benzo[d]oxazole derivative 1	DMNIPE6	N. A.	N. A.	Patented	[8]
Benzo[d]oxazole derivative 2	DMR5V2A	N. A.	N. A.	Patented	[8]
Benzo[d]oxazole derivative 3	DM712Y0	N. A.	N. A.	Patented	[8]
Benzo[d]oxazole derivative 4	DM0RAC6	N. A.	N. A.	Patented	[8]
Chalcone derivative 1	DMSMBCO	N. A.	N. A.	Patented	[8]
Chalcone derivative 2	DMG84D3	N. A.	N. A.	Patented	[8]
Chalcone derivative 3	DMFS7C3	N. A.	N. A.	Patented	[8]
Chalcone derivative 4	DM45COR	N. A.	N. A.	Patented	[8]
Diterpenoid derivative 1	DMAZOH4	N. A.	N. A.	Patented	[8]
Diterpenoid derivative 2	DMKT19M	N. A.	N. A.	Patented	[8]
Naphthalene derivative 1	DMWLPEB	N. A.	N. A.	Patented	[8]
PMID28454500-Compound-10	DMD9W6H	N. A.	N. A.	Patented	[8]
PMID28454500-Compound-11	DM1ZFC9	N. A.	N. A.	Patented	[8]
PMID28454500-Compound-12	DMUY4LS	N. A.	N. A.	Patented	[8]
PMID28454500-Compound-13	DM7SIVA	N. A.	N. A.	Patented	[8]
PMID28454500-Compound-3	DMAGVHX	N. A.	N. A.	Patented	[8]
PMID28454500-Compound-32	DMAIGJP	N. A.	N. A.	Patented	[8]
PMID28454500-Compound-33	DMYXQU3	N. A.	N. A.	Patented	[8]
PMID28454500-Compound-34	DMN2910	N. A.	N. A.	Patented	[8]
PMID28454500-Compound-35	DM2OM4Z	N. A.	N. A.	Patented	[8]
PMID28454500-Compound-36	DM5RZWG	N. A.	N. A.	Patented	[8]
PMID28454500-Compound-37	DM83P6H	N. A.	N. A.	Patented	[8]
PMID28454500-Compound-40	DM9TVWJ	N. A.	N. A.	Patented	[8]
PMID28454500-Compound-41	DMGAW81	N. A.	N. A.	Patented	[8]
PMID28454500-Compound-49	DM5NJDK	N. A.	N. A.	Patented	[8]
PMID28454500-Compound-50	DMQPKCD	N. A.	N. A.	Patented	[8]
PMID28454500-Compound-57	DMTK9M6	N. A.	N. A.	Patented	[8]
PMID28454500-Compound-58	DMDEHYR	N. A.	N. A.	Patented	[8]
PMID28454500-Compound-59	DMQWPSF	N. A.	N. A.	Patented	[8]
PMID28454500-Compound-60	DM1I9JC	N. A.	N. A.	Patented	[8]
PMID28454500-Compound-8	DM6BQFA	N. A.	N. A.	Patented	[8]
PMID28454500-Compound-9	DM3HR7F	N. A.	N. A.	Patented	[8]
PMID28454500-Compound-91	DMJ1KFO	N. A.	N. A.	Patented	[8]
PMID28454500-Compound-92	DM1RS4X	N. A.	N. A.	Patented	[8]
PMID28454500-Compound-93	DMMDK6B	N. A.	N. A.	Patented	[8]
PMID28454500-Compound-94	DM5Q962	N. A.	N. A.	Patented	[8]
PMID28454500-Compound-95	DM9L2VR	N. A.	N. A.	Patented	[8]
PMID28454500-Compound-96	DM2A75P	N. A.	N. A.	Patented	[8]
Pyrazino[2,1-a]isoquinolin derivative 1	DMP1MDV	N. A.	N. A.	Patented	[8]
Pyrazino[2,1-a]isoquinolin derivative 2	DMYXKQ3	N. A.	N. A.	Patented	[8]
Pyrazino[2,1-a]isoquinolin derivative 3	DMXYU3I	N. A.	N. A.	Patented	[8]
Pyrazino[2,1-a]isoquinolin derivative 4	DMKTNBC	N. A.	N. A.	Patented	[8]
Pyridyl compound 1	DMUTE5S	N. A.	N. A.	Patented	[8]
Thiazole derivative 2	DM8ZXBS	N. A.	N. A.	Patented	[8]
Thiazole derivative 3	DMKU51G	N. A.	N. A.	Patented	[8]
Trepenoid derivative 1	DM6KJLG	N. A.	N. A.	Patented	[8]
Vinyl sulfone derivative 1	DMTMFNK	N. A.	N. A.	Patented	[8]

3 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
CAT4001	DMDUKMR	Alpha-1 antitrypsin deficiency	5C5A	Preclinical	[6]
M102	DMUFIO9	Amyotrophic lateral sclerosis	8B60.0	Preclinical	[9]
TFM735	DMY8QP5	Multiple sclerosis	8A40	Preclinical	[10]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Lung cancer	2C82	Lung tissue	4.75E-12	-0.28	-0.58

References

• [1] National Cancer Institute Drug Dictionary (drug id 756624).
• [2] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [3] The Keap1-Nrf2 pathway: promising therapeutic target to counteract ROS-mediated damage in cancers and neurodegenerative diseases. Biophys Rev. 2017 Feb;9(1):41-56.
• [4] New hope for dry AMD. Nat Rev Drug Discov. 2013 Jul;12(7):501-2.
• [5] Nitroxide pharmaceutical development for age-related degeneration and disease. Front Genet. 2015 Nov 6;6:325.
• [6] Therapeutic targeting of the NRF2 and KEAP1 partnership in chronic diseases. Nat Rev Drug Discov. 2019 Apr;18(4):295-317.
• [7] Clinical pipeline report, company report or official report of vTv Therapeutics.
• [8] Recent progress in the development of small molecule Nrf2 modulators: a patent review (2012-2016).Expert Opin Ther Pat. 2017 Jul;27(7):763-785.
• [9] Clinical pipeline report, company report or official report of Aclipse Therapeutics.
• [10] The novel Nrf2 inducer TFM-735 ameliorates experimental autoimmune encephalomyelitis in mice. Eur J Pharmacol. 2017 May 5;802:76-84.