Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT956B0)

• DTT Name: Keap1-Nrf2[DLG] PPI (KEAP1-Nrf2 DLG)
• Synonyms: Kelch-like protein 19-Nrf2[DLG]; Kelch-like ECH-associated protein 1-Nrf2[DLG]; KLHL19-Nrf2[DLG]; KIAA0132-Nrf2[DLG]; INrf2-Nrf2[DLG]; Cytosolic inhibitor of Nrf2-Nrf2[DLG]
• Gene Name: KEAP1-NFE2L2
• DTT Type: Patented-recorded target; [1]
• UniProt ID: KEAP1_HUMAN-NF2L2_HUMAN
• TTD ID: T80959
• Sequence:
  MQPDPRPSGAGACCRFLPLQSQCPEGAGDAVMYASTECKAEVTPSQHGNRTFSYTLEDHT
  KQAFGIMNELRLSQQLCDVTLQVKYQDAPAAQFMAHKVVLASSSPVFKAMFTNGLREQGM
  EVVSIEGIHPKVMERLIEFAYTASISMGEKCVLHVMNGAVMYQIDSVVRACSDFLVQQLD
  PSNAIGIANFAEQIGCVELHQRAREYIYMHFGEVAKQEEFFNLSHCQLVTLISRDDLNVR
  CESEVFHACINWVKYDCEQRRFYVQALLRAVRCHSLTPNFLQMQLQKCEILQSDSRCKDY
  LVKIFEELTLHKPTQVMPCRAPKVGRLIYTAGGYFRQSLSYLEAYNPSDGTWLRLADLQV
  PRSGLAGCVVGGLLYAVGGRNNSPDGNTDSSALDCYNPMTNQWSPCAPMSVPRNRIGVGV
  IDGHIYAVGGSHGCIHHNSVERYEPERDEWHLVAPMLTRRIGVGVAVLNRLLYAVGGFDG
  TNRLNSAECYYPERNEWRMITAMNTIRSGAGVCVLHNCIYAAGGYDGQDQLNSVERYDVE
  TETWTFVAPMKHRRSALGITVHQGRIYVLGGYDGHTFLDSVECYDPDTDTWSEVTRMTSG
  RSGVGVAVTMEPCRKQIDQQNCTCMMDLELPPPGLPSQQDMDLIDILWRQDIDLGVSREV
  FDFSQRRKEYELEKQKKLEKERQEQLQKEQEKAFFAQLQLDEETGEFLPIQPAQHIQSET
  SGSANYSQVAHIPKSDALYFDDCMQLLAQTFPFVDDNEVSSATFQSLVPDIPGHIESPVF
  IATNQAQSPETSVAQVAPVDLDGMQQDIEQVWEELLSIPELQCLNIENDKLVETTMVPSP
  EAKLTEVDNYHFYSSIPSMEKEVGNCSPHFLNAFEDSFSSILSTEDPNQLTVNSLNSDAT
  VNTDFGDEFYSAFIAEPSISNSMPSPATLSHSLSELLNGPIDVSDLSLCKAFNQNHPEST
  AEFNDSDSGISLNTSPSVASPEHSVESSSYGDTLLGLSDSEVEELDSAPGSVKQNGPKTP
  VHSSGDMVQPLSPSQGQSTHVHDAQCENTPEKELPVSPGHRKTPFTKDKHSSRLEAHLTR
  DELRAKALHIPFPVEKIINLPVVDFNEMMSKEQFNEAQLALIRDIRRRGKNKVAAQNCRK
  RKLENIVELEQDLDHLKDEKEKLLKEKGENDKSLHLLKKQLSTLYLEVFSMLRDEDGKPY
  SPSEYSLQQTRDGNVFLVPKSKKPDVKKN
• 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.

Molecular Interaction Atlas (MIA) of This DTT

3 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
1-phenyl-1,3,4-triazole derivative 1	DMS5EHL	N. A.	N. A.	Patented	[1]
1-phenyl-1,3,4-triazole derivative 2	DMO7310	N. A.	N. A.	Patented	[1]
1-phenyl-1,3,4-triazole derivative 3	DMU8FC1	N. A.	N. A.	Patented	[1]

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.