Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTKT026)

• DTT Name: NLR family member X1 (NLRX1)
• Synonyms: Caterpiller protein 11.3; CLR11.3; Nucleotide-binding oligomerization domain protein 5; Nucleotide-binding oligomerization domain protein 9
• Gene Name: NLRX1
• DTT Type: Clinical trial target; [1]
• BioChemical Class: NLRP family
• UniProt ID: NLRX1_HUMAN
• TTD ID: T63211
• Sequence:
  MRWGHHLPRASWGSGFRRALQRPDDRIPFLIHWSWPLQGERPFGPPRAFIRHHGSSVDSA
  PPPGRHGRLFPSASATEAIQRHRRNLAEWFSRLPREERQFGPTFALDTVHVDPVIRESTP
  DELLRPPAELALEHQPPQAGLPPLALSQLFNPDACGRRVQTVVLYGTVGTGKSTLVRKMV
  LDWCYGRLPAFELLIPFSCEDLSSLGPAPASLCQLVAQRYTPLKEVLPLMAAAGSHLLFV
  LHGLEHLNLDFRLAGTGLCSDPEEPQEPAAIIVNLLRKYMLPQASILVTTRPSAIGRIPS
  KYVGRYGEICGFSDTNLQKLYFQLRLNQPYCGYAVGGSGVSATPAQRDHLVQMLSRNLEG
  HHQIAAACFLPSYCWLVCATLHFLHAPTPAGQTLTSIYTSFLRLNFSGETLDSTDPSNLS
  LMAYAARTMGKLAYEGVSSRKTYFSEEDVCGCLEAGIRTEEEFQLLHIFRRDALRFFLAP
  CVEPGRAGTFVFTVPAMQEYLAALYIVLGLRKTTLQKVGKEVAELVGRVGEDVSLVLGIM
  AKLLPLRALPLLFNLIKVVPRVFGRMVGKSREAVAQAMVLEMFREEDYYNDDVLDQMGAS
  ILGVEGPRRHPDEPPEDEVFELFPMFMGGLLSAHNRAVLAQLGCPIKNLDALENAQAIKK
  KLGKLGRQVLPPSELLDHLFFHYEFQNQRFSAEVLSSLRQLNLAGVRMTPVKCTVVAAVL
  GSGRHALDEVNLASCQLDPAGLRTLLPVFLRARKLGLQLNSLGPEACKDLRDLLLHDQCQ
  ITTLRLSNNPLTAAGVAVLMEGLAGNTSVTHLSLLHTGLGDEGLELLAAQLDRNRQLQEL
  NVAYNGAGDTAALALARAAREHPSLELLHLYFNELSSEGRQVLRDLGGAAEGGARVVVSL
  TEGTAVSEYWSVILSEVQRNLNSWDRARVQRHLELLLRDLEDSRGATLNPWRKAQLLRVE
  GEVRALLEQLGSSGS
• Function: Participates in antiviral signaling. Acts as a negative regulator of MAVS-mediated antiviral responses, through the inhibition of the virus-induced RLH (RIG-like helicase)-MAVS interaction (PubMed:18200010). Instead, promotes autophagy by interacting with TUFM and subsequently recruiting the autophagy-related proteins ATG5 and ATG12 (PubMed:22749352). Regulates also MAVS-dependent NLRP3 inflammasome activation to attenuate apoptosis (PubMed:27393910). Has no inhibitory function on NF-kappa-B signaling pathway, but enhances NF-kappa-B and JUN N-terminal kinase dependent signaling through the production of reactive oxygen species (PubMed:18219313). Regulates viral mediated-inflammation and energy metabolism in a sex-dependent manner (By similarity). In females, prevents uncontrolled inflammation and energy metabolism and thus, may contribute to the sex differences observed in infectious and inflammatory diseases (By similarity). {ECO:0000250|UniProtKB:Q3TL44, ECO:0000269|PubMed:18200010, ECO:0000269|PubMed:18219313, ECO:0000269|PubMed:22749352, ECO:0000269|PubMed:27393910}.
• KEGG Pathway: 79671 (hsa)
• Reactome Pathway:
  (R-HSA-168928)
  (R-HSA-936440)
  (R-HSA-9758274)

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
NX-13	DMLIAA7	Ulcerative colitis	DD71	Phase 2	[1]

References

• [1] Exploratory studies with NX-13: oral toxicity and pharmacokinetics in rodents of an orally active, gut-restricted first-in-class therapeutic for IBD that targets NLRX1. Drug Chem Toxicol. 2022 Jan;45(1):209-214.