Details of the Drug Therapeutic Target (DTT)

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

• DTT Name: Delta-aminolevulinic acid dehydratase (ALAD)
• Synonyms: Porphobilinogen synthase; Delta-aminolevulinate dehydratase; ALADH; ALAD
• Gene Name: ALAD
• DTT Type: Successful target; [1]
• BioChemical Class: Alpha-carbonic anhydrase
• UniProt ID: HEM2_HUMAN
• TTD ID: T20514
• EC Number: EC 4.2.1.24
• Sequence:
  MQPQSVLHSGYFHPLLRAWQTATTTLNASNLIYPIFVTDVPDDIQPITSLPGVARYGVKR
  LEEMLRPLVEEGLRCVLIFGVPSRVPKDERGSAADSEESPAIEAIHLLRKTFPNLLVACD
  VCLCPYTSHGHCGLLSENGAFRAEESRQRLAEVALAYAKAGCQVVAPSDMMDGRVEAIKE
  ALMAHGLGNRVSVMSYSAKFASCFYGPFRDAAKSSPAFGDRRCYQLPPGARGLALRAVDR
  DVREGADMLMVKPGMPYLDIVREVKDKHPDLPLAVYHVSGEFAMLWHGAQAGAFDLKAAV
  LEAMTAFRRAGADIIITYYTPQLLQWLKEE
• Function: Catalyzes an early step in the biosynthesis of tetrapyrroles. Binds two molecules of 5-aminolevulinate per subunit, each at a distinct site, and catalyzes their condensation to form porphobilinogen.
• KEGG Pathway:
  Porphyrin and chlorophyll metabolism (hsa00860)
  Metabolic pathways (hsa01100)
• Reactome Pathway:
  Neutrophil degranulation (R-HSA-6798695)
  Heme biosynthesis (R-HSA-189451)
• BioCyc Pathway: MetaCyc:HS07501-MON

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Aminolevulinic acid hci	DMS4BLQ	Acne vulgaris	ED80	Approved	[1]

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Porphobilinogen	DM5HMTB	N. A.	N. A.	Phase 2	[2]

10 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
2-Sulfhydryl-Ethanol	DMJBO3D	Discovery agent	N.A.	Investigative	[2]
3-(2-Aminoethyl)-4-(Aminomethyl)Heptanedioic Acid	DMQXPM3	Discovery agent	N.A.	Investigative	[2]
4,7-Dioxosebacic Acid	DML5302	Discovery agent	N.A.	Investigative	[2]
4-Oxosebacic Acid	DMADSUY	Discovery agent	N.A.	Investigative	[2]
5-Fluorolevulinic Acid	DMDV48S	Discovery agent	N.A.	Investigative	[2]
5-hydroxyvaleric acid	DMIXQG6	Discovery agent	N.A.	Investigative	[3]
Delta-Amino Valeric Acid	DMV7IAK	Discovery agent	N.A.	Investigative	[2]
Formic Acid	DMNFZC6	Discovery agent	N.A.	Investigative	[2]
Laevulinic Acid	DMTZ17V	Discovery agent	N.A.	Investigative	[2]
S,S-(2-Hydroxyethyl)Thiocysteine	DMLPAD8	Discovery agent	N.A.	Investigative	[2]

The Drug-Metabolizing Enzyme (DME) Role of This DTT

• DTT DME Name: Porphobilinogen synthase (ALAD) DME Info
• Gene Name: ALAD

1 Approved Drug(s) Metabolized by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Aminolevulinic acid hci	DMS4BLQ	Acne vulgaris	ED80	Approved	[4]

References

• [1] Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides. Nat Biotechnol. 2003 May;21(5):566-9.
• [2] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [3] Structure of yeast 5-aminolaevulinic acid dehydratase complexed with the inhibitor 5-hydroxylaevulinic acid. Acta Crystallogr D Biol Crystallogr. 2005 Sep;61(Pt 9):1222-6.
• [4] Modifying effects of delta-Aminolevulinate dehydratase polymorphism on blood lead levels and ALAD activity. Toxicol Lett. 2018 Oct 1;295:351-356.