Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT4D7MJ)

• DTT Name: Serine/threonine-protein kinase ULK1 (ULK1)
• Synonyms: hATG1; Unc-51-like kinase 1; KIAA0722; Autophagy-related protein 1 homolog; ATG1
• Gene Name: ULK1
• DTT Type: Literature-reported target; [1]
• BioChemical Class: Kinase
• UniProt ID: ULK1_HUMAN
• TTD ID: T79307
• EC Number: EC 2.7.11.1
• Sequence:
  MEPGRGGTETVGKFEFSRKDLIGHGAFAVVFKGRHREKHDLEVAVKCINKKNLAKSQTLL
  GKEIKILKELKHENIVALYDFQEMANSVYLVMEYCNGGDLADYLHAMRTLSEDTIRLFLQ
  QIAGAMRLLHSKGIIHRDLKPQNILLSNPAGRRANPNSIRVKIADFGFARYLQSNMMAAT
  LCGSPMYMAPEVIMSQHYDGKADLWSIGTIVYQCLTGKAPFQASSPQDLRLFYEKNKTLV
  PTIPRETSAPLRQLLLALLQRNHKDRMDFDEFFHHPFLDASPSVRKSPPVPVPSYPSSGS
  GSSSSSSSTSHLASPPSLGEMQQLQKTLASPADTAGFLHSSRDSGGSKDSSCDTDDFVMV
  PAQFPGDLVAEAPSAKPPPDSLMCSGSSLVASAGLESHGRTPSPSPPCSSSPSPSGRAGP
  FSSSRCGASVPIPVPTQVQNYQRIERNLQSPTQFQTPRSSAIRRSGSTSPLGFARASPSP
  PAHAEHGGVLARKMSLGGGRPYTPSPQVGTIPERPGWSGTPSPQGAEMRGGRSPRPGSSA
  PEHSPRTSGLGCRLHSAPNLSDLHVVRPKLPKPPTDPLGAVFSPPQASPPQPSHGLQSCR
  NLRGSPKLPDFLQRNPLPPILGSPTKAVPSFDFPKTPSSQNLLALLARQGVVMTPPRNRT
  LPDLSEVGPFHGQPLGPGLRPGEDPKGPFGRSFSTSRLTDLLLKAAFGTQAPDPGSTESL
  QEKPMEIAPSAGFGGSLHPGARAGGTSSPSPVVFTVGSPPSGSTPPQGPRTRMFSAGPTG
  SASSSARHLVPGPCSEAPAPELPAPGHGCSFADPITANLEGAVTFEAPDLPEETLMEQEH
  TEILRGLRFTLLFVQHVLEIAALKGSASEAAGGPEYQLQESVVADQISLLSREWGFAEQL
  VLYLKVAELLSSGLQSAIDQIRAGKLCLSSTVKQVVRRLNELYKASVVSCQGLSLRLQRF
  FLDKQRLLDRIHSITAERLIFSHAVQMVQSAALDEMFQHREGCVPRYHKALLLLEGLQHM
  LSDQADIENVTKCKLCIERRLSALLTGICA
• Function: Acts upstream of phosphatidylinositol 3-kinase PIK3C3 to regulate the formation of autophagophores, the precursors of autophagosomes. Part of regulatory feedback loops in autophagy: acts both as a downstream effector and negative regulator of mammalian target of rapamycin complex 1 (mTORC1) via interaction with RPTOR. Activated via phosphorylation by AMPK and also acts as a regulator of AMPK by mediating phosphorylation of AMPK subunits PRKAA1, PRKAB2 and PRKAG1, leading to negatively regulate AMPK activity. May phosphorylate ATG13/KIAA0652 and RPTOR; however such data need additional evidences. Plays a role early in neuronal differentiation and is required for granule cell axon formation. May also phosphorylate SESN2 and SQSTM1 to regulate autophagy. Serine/threonine-protein kinase involved in autophagy in response to starvation.
• KEGG Pathway:
  Mitophagy - animal (hsa04137)
  Autophagy - animal (hsa04140)
  mTOR signaling pathway (hsa04150)
  AMPK signaling pathway (hsa04152)
  Longevity regulating pathway (hsa04211)
  Alzheimer disease (hsa05010)
  Amyotrophic lateral sclerosis (hsa05014)
  Huntington disease (hsa05016)
  Spinocerebellar ataxia (hsa05017)
  Pathways of neurodegeneration - multiple diseases (hsa05022)
• Reactome Pathway:
  TBC/RABGAPs (R-HSA-8854214)
  RAB GEFs exchange GTP for GDP on RABs (R-HSA-8876198)
  Receptor Mediated Mitophagy (R-HSA-8934903)
  Macroautophagy (R-HSA-1632852)

Molecular Interaction Atlas (MIA) of This DTT

1 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PMID21967808CR-16	DMCOHKU	Discovery agent	N.A.	Investigative	[1]

References

• [1] Improvement in oral bioavailability of 2,4-diaminopyrimidine c-Met inhibitors by incorporation of a 3-amidobenzazepin-2-one group. Bioorg Med Chem. 2011 Nov 1;19(21):6274-84.