Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT3Z6Y9)

• DTT Name: Cysteines of Keap1 (KEAP1 Cysteines)
• Synonyms: Kelch-like protein 19-Cysteines; Kelch-like ECH-associated protein 1-Cysteines; KLHL19-Cysteines; KIAA0132-Cysteines; INrf2-Cysteines; Cytosolic inhibitor of Nrf2-Cysteines
• Gene Name: KEAP1
• DTT Type: Clinical trial target; [1]
• UniProt ID: KEAP1_HUMAN
• TTD ID: T83198
• Sequence:
  MQPDPRPSGAGACCRFLPLQSQCPEGAGDAVMYASTECKAEVTPSQHGNRTFSYTLEDHT
  KQAFGIMNELRLSQQLCDVTLQVKYQDAPAAQFMAHKVVLASSSPVFKAMFTNGLREQGM
  EVVSIEGIHPKVMERLIEFAYTASISMGEKCVLHVMNGAVMYQIDSVVRACSDFLVQQLD
  PSNAIGIANFAEQIGCVELHQRAREYIYMHFGEVAKQEEFFNLSHCQLVTLISRDDLNVR
  CESEVFHACINWVKYDCEQRRFYVQALLRAVRCHSLTPNFLQMQLQKCEILQSDSRCKDY
  LVKIFEELTLHKPTQVMPCRAPKVGRLIYTAGGYFRQSLSYLEAYNPSDGTWLRLADLQV
  PRSGLAGCVVGGLLYAVGGRNNSPDGNTDSSALDCYNPMTNQWSPCAPMSVPRNRIGVGV
  IDGHIYAVGGSHGCIHHNSVERYEPERDEWHLVAPMLTRRIGVGVAVLNRLLYAVGGFDG
  TNRLNSAECYYPERNEWRMITAMNTIRSGAGVCVLHNCIYAAGGYDGQDQLNSVERYDVE
  TETWTFVAPMKHRRSALGITVHQGRIYVLGGYDGHTFLDSVECYDPDTDTWSEVTRMTSG
  RSGVGVAVTMEPCRKQIDQQNCTC
• Function: Retains NFE2L2/NRF2 and may also retain BPTF in the cytosol. Targets PGAM5 for ubiquitination and degradation by the proteasome. Acts as a substrate adapter protein for the E3 ubiquitin ligase complex formed by CUL3 and RBX1 and targets NFE2L2/NRF2 for ubiquitination and degradation by the proteasome, thus resulting in the suppression of its transcriptional activity and the repression of antioxidant response element-mediated detoxifying enzyme gene expression.
• KEGG Pathway:
  Ubiquitin mediated proteolysis (hsa04120)
  Parkinson disease (hsa05012)
  Pathways in cancer (hsa05200)
  Chemical carcinogenesis - reactive oxygen species (hsa05208)
  Hepatocellular carcinoma (hsa05225)
  Fluid shear stress and atherosclerosis (hsa05418)
• Reactome Pathway:
  Neddylation (R-HSA-8951664)
  Potential therapeutics for SARS (R-HSA-9679191)
  KEAP1-NFE2L2 pathway (R-HSA-9755511)
  Antigen processing (R-HSA-983168)
  Ub-specific processing proteases (R-HSA-5689880)

Molecular Interaction Atlas (MIA) of This DTT

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
CXA10	DMM7Z6K	Focal segmental glomerulosclerosis	MF8Y	Phase 2	[2]

32 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
2-hydroxybenzamide derivative 1	DMER2ZQ	N. A.	N. A.	Patented	[1]
2-hydroxybenzamide derivative 2	DM9FRN6	N. A.	N. A.	Patented	[1]
Chalcone derivative 1	DMSMBCO	N. A.	N. A.	Patented	[1]
Chalcone derivative 2	DMG84D3	N. A.	N. A.	Patented	[1]
Chalcone derivative 3	DMFS7C3	N. A.	N. A.	Patented	[1]
Chalcone derivative 4	DM45COR	N. A.	N. A.	Patented	[1]
Diterpenoid derivative 1	DMAZOH4	N. A.	N. A.	Patented	[1]
Diterpenoid derivative 2	DMKT19M	N. A.	N. A.	Patented	[1]
PMID28454500-Compound-10	DMD9W6H	N. A.	N. A.	Patented	[1]
PMID28454500-Compound-11	DM1ZFC9	N. A.	N. A.	Patented	[1]
PMID28454500-Compound-12	DMUY4LS	N. A.	N. A.	Patented	[1]
PMID28454500-Compound-13	DM7SIVA	N. A.	N. A.	Patented	[1]
PMID28454500-Compound-3	DMAGVHX	N. A.	N. A.	Patented	[1]
PMID28454500-Compound-32	DMAIGJP	N. A.	N. A.	Patented	[1]
PMID28454500-Compound-33	DMYXQU3	N. A.	N. A.	Patented	[1]
PMID28454500-Compound-34	DMN2910	N. A.	N. A.	Patented	[1]
PMID28454500-Compound-35	DM2OM4Z	N. A.	N. A.	Patented	[1]
PMID28454500-Compound-36	DM5RZWG	N. A.	N. A.	Patented	[1]
PMID28454500-Compound-37	DM83P6H	N. A.	N. A.	Patented	[1]
PMID28454500-Compound-40	DM9TVWJ	N. A.	N. A.	Patented	[1]
PMID28454500-Compound-41	DMGAW81	N. A.	N. A.	Patented	[1]
PMID28454500-Compound-49	DM5NJDK	N. A.	N. A.	Patented	[1]
PMID28454500-Compound-50	DMQPKCD	N. A.	N. A.	Patented	[1]
PMID28454500-Compound-8	DM6BQFA	N. A.	N. A.	Patented	[1]
PMID28454500-Compound-9	DM3HR7F	N. A.	N. A.	Patented	[1]
Pyrazino[2,1-a]isoquinolin derivative 1	DMP1MDV	N. A.	N. A.	Patented	[1]
Pyrazino[2,1-a]isoquinolin derivative 2	DMYXKQ3	N. A.	N. A.	Patented	[1]
Pyrazino[2,1-a]isoquinolin derivative 3	DMXYU3I	N. A.	N. A.	Patented	[1]
Pyrazino[2,1-a]isoquinolin derivative 4	DMKTNBC	N. A.	N. A.	Patented	[1]
Pyridyl compound 1	DMUTE5S	N. A.	N. A.	Patented	[1]
Trepenoid derivative 1	DM6KJLG	N. A.	N. A.	Patented	[1]
Vinyl sulfone derivative 1	DMTMFNK	N. A.	N. A.	Patented	[1]

2 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
VCB101	DMUO6XC	Multiple sclerosis	8A40	Preclinical	[3]
VCB102	DMR3XDH	Psoriasis vulgaris	EA90	Preclinical	[3]

References

• [1] 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.
• [2] 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.
• [3] NRF2 Regulation Processes as a Source of Potential Drug Targets against Neurodegenerative Diseases. Biomolecules. 2020 Jun 14;10(6):904.