Details of the Drug

General Information of Drug (ID: DMS4BLQ)

• Drug Name: Aminolevulinic acid hci
• Synonyms: Aminolevulinic acid; 5-Aminolevulinic acid; 5-Amino-4-oxopentanoic acid; 106-60-5; 5-Aminolevulinate; delta-aminolevulinic acid; Pentanoic acid, 5-amino-4-oxo-; Aladerm; 5-Amino-4-oxovaleric acid; Kerastick; Ameluz; Aminolevulinate; 5-ALA; delta-ALA; 5-Amino-4-oxopentanoate; 5-amino-levulinate; 5-amino-levulinic acid; 5-amino-4-oxo-pentanoic acid; CCRIS 8958; UNII-88755TAZ87; EINECS 203-414-1; Levulinic acid, 5-amino-; CHEMBL601; 4-oxo-5-amino-pentanoic acid; CHEBI:17549; ZGXJTSGNIOSYLO-UHFFFAOYSA-N; 88755TAZ87; Levulan (TN)

Indication

Disease Entry	ICD 11	Status	REF
Acne vulgaris	ED80	Approved	[1]
Actinic keratosis	EK90.0	Approved	[2]
Astrocytoma	2A00.0Y	Approved	[3]
Glioblastoma	2A00	Approved	[4]
Malignant glioma	2A00.0	Approved	[5]
Oral mucosa leukoplakia	N.A.	Approved	[6]
Adult glioblastoma	N.A.	Investigative	[7]
Cervical Intraepithelial neoplasia	2E66.1	Investigative	[8]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 1:
  Molecular Weight (mw); 131.13
  Logarithm of the Partition Coefficient (xlogp); -3.8
  Rotatable Bond Count (rotbonds); 4
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 4
• ADMET Property:
  Bioavailability: The bioavailability of drug is 50-60% []
  Clearance: The drug present in the plasma can be removed from the body at the rate of 1.88 mL/min/kg [9]
  Half-life: The concentration or amount of drug in body reduced by one-half in 0.70 +/-0.18 hours [9]
  Metabolism: The drug is metabolized via skin []
  Unbound Fraction: The unbound fraction of drug in plasma is 0.88% [9]
  Vd: Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 0.12 L/kg [9]
• Chemical Identifiers:
  Formula: C5H9NO3
  IUPAC Name: 5-amino-4-oxopentanoic acid
  Canonical SMILES: C(CC(=O)O)C(=O)CN
  InChI: InChI=1S/C5H9NO3/c6-3-4(7)1-2-5(8)9/h1-3,6H2,(H,8,9)
  InChIKey: ZGXJTSGNIOSYLO-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 137
  ChEBI ID: CHEBI:17549
  CAS Number: 106-60-5
  DrugBank ID: DB00855
  TTD ID: D0Y7ZD
  VARIDT ID: DR00057
  INTEDE ID: DR0088
• Repurposed Drugs (RPD): Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Delta-aminolevulinic acid dehydratase (ALAD)	TTJHKYD	HEM2_HUMAN	Inhibitor	[10]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Peptide transporter 2 (SLC15A2)	DT8QKNP	S15A2_HUMAN	Substrate	[11]
Proton-coupled amino acid transporter 1 (SLC36A1)	DT48WEM	S36A1_HUMAN	Substrate	[12]
Peptide transporter 1 (SLC15A1)	DT9G7XN	S15A1_HUMAN	Substrate	[13]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Porphobilinogen synthase (ALAD) Main DME	DETBNY4	HEM2_HUMAN	Substrate	[14]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Gene/Protein Processing	[15]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Gene/Protein Processing	[15]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Gene/Protein Processing	[16]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Gene/Protein Processing	[17]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Gene/Protein Processing	[18]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Gene/Protein Processing	[19]
FAS-associated death domain protein (FADD)	OTV7GFHH	FADD_HUMAN	Post-Translational Modifications	[17]
Interstitial collagenase (MMP1)	OTI4I2V1	MMP1_HUMAN	Gene/Protein Processing	[20]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Protein Interaction/Cellular Processes	[17]
Stromelysin-1 (MMP3)	OTGBI74Z	MMP3_HUMAN	Gene/Protein Processing	[20]

References

• [1] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 4784).
• [2] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [3] Physical approaches to treat glioblastoma. Curr Opin Oncol. 2020 Nov;32(6):640-649.
• [4] Comparison of commercial 5-aminolevulinic acid (Gliolan?) and the pharmacy-compounded solution fluorescence in glioblastoma. Acta Neurochir (Wien). 2019 Aug;161(8):1733-1741.
• [5] Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial. Lancet Oncol. 2006 May;7(5):392-401.
• [6] Vascular alterations after photodynamic therapy mediated by 5-aminolevulinic acid in oral leukoplakia. Lasers Med Sci. 2017 Feb;32(2):379-387.
• [7] 5-Aminolevulinic acid-guided resection improves the overall survival of patients with glioblastoma-a comparative cohort study of 343 patients. Neurooncol Adv. 2021 Mar 26;3(1):vdab047.
• [8] Photodetection and Safety of 5-Aminolevulinic Acid-Induced Porphyrin in Patients With Cervical Intraepithelial Neoplasia. Lasers Surg Med. 2021 Jul;53(5):654-663.
• [9] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [10] Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides. Nat Biotechnol. 2003 May;21(5):566-9.
• [11] PEPT2-mediated transport of 5-aminolevulinic acid and carnosine in astrocytes. Brain Res. 2006 Nov 29;1122(1):18-23.
• [12] Delta-aminolevulinic acid is a substrate for the amino acid transporter SLC36A1 (hPAT1). Br J Pharmacol. 2010 Mar;159(6):1339-53.
• [13] Transport of the photodynamic therapy agent 5-aminolevulinic acid by distinct H+-coupled nutrient carriers coexpressed in the small intestine. J Pharmacol Exp Ther. 2010 Jan;332(1):220-8.
• [14] Modifying effects of delta-Aminolevulinate dehydratase polymorphism on blood lead levels and ALAD activity. Toxicol Lett. 2018 Oct 1;295:351-356.
• [15] Effect and mechanism of 5-aminolevulinic acid-mediated photodynamic therapy in esophageal cancer. Lasers Med Sci. 2011 Jan;26(1):69-78. doi: 10.1007/s10103-010-0810-0. Epub 2010 Jul 30.
• [16] Photodynamic therapy with 5-aminolevulinic acid induces apoptosis and caspase activation in malignant T cells. J Cutan Med Surg. 2001 Jan-Feb;5(1):8-13. doi: 10.1177/120347540100500103.
• [17] 5-aminolevulinic acid induce apoptosis via NF-B/JNK pathway in human oral cancer Ca9-22 cells. J Oral Pathol Med. 2011 Jul;40(6):483-9. doi: 10.1111/j.1600-0714.2010.00973.x. Epub 2010 Dec 8.
• [18] Massive apoptotic cell death of human glioma cells via a mitochondrial pathway following 5-aminolevulinic acid-mediated photodynamic therapy. J Neurooncol. 2007 Jul;83(3):223-31. doi: 10.1007/s11060-006-9325-8. Epub 2007 Jan 24.
• [19] Study of the efficacy and mechanism of ALA-mediated photodynamic therapy on human hepatocellular carcinoma cell. Liver Int. 2007 Mar;27(2):201-8. doi: 10.1111/j.1478-3231.2006.01412.x.
• [20] Influence of 5-aminolevulinic acid and red light on collagen metabolism of human dermal fibroblasts. J Invest Dermatol. 2003 Feb;120(2):325-31. doi: 10.1046/j.1523-1747.2003.12037.x.