Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMK1CZJ)

• Drug Name: Ingenol mebutate Drug Info
• Synonyms: Picato; Ingenol 3-angelate; 75567-37-2; PEP-005; PEP005; 3-Angeloylingenol; UNII-7686S50JAH; PEP 005; 3-Ingenyl angelate; Ingenol-3-angelate; 7686S50JAH; Picato (TN); Euphorbia factor H1; Euphorbia factor An1; Ingenol mebutate [USAN:INN]; [dihydroxy-(hydroxymethyl)-tetramethyl-oxo-[ ]yl] (Z)-2-methylbut-2-enoate; I3A; Ingenol-3- angelate; Ingenol mebutate (USAN); (Z)-2-methylbut-2-enoate; SCHEMBL2526605; GTPL7443; CHEMBL1863513; HSDB 8308; VDJHFHXMUKFKET-WDUFCVPESA-N; MolPort-003-941-761; AN-262; POL-103A

Indication

Disease Entry	ICD 11	Status	REF
Actinic keratosis	EK90.0	Approved	[1]
Melanoma	2C30	Phase 3	[2]

• Cross-matching ID:
  PubChem CID: 6918670
  ChEBI ID: CHEBI:66913
  CAS Number: CAS 75567-37-2
  TTD Drug ID: DMK1CZJ
  VARIDT Drug ID: DR01483
  ACDINA Drug ID: D01160

Molecule-Related Drug Atlas

Drug(s) Transported By P-glycoprotein 1 (ABCB1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Amoxicillin	DMUYNEI	Acute otitis media	AB00	Approved	[5]
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[6]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[7]
Folic Acid	DMEMBJC	Colorectal carcinoma		Approved	[8]
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[7]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[7]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[9]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[7]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[10]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[11]

Drug(s) Affected By Protein S100-A4 (S100A4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[12]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[13]
Isotretinoin	DM4QTBN	Acne vulgaris	ED80	Approved	[14]
Panobinostat	DM58WKG	Chronic graft versus host disease		Approved	[15]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[16]
Aspirin	DM672AH	Acute coronary syndrome	BA41	Approved	[17]
Adenosine triphosphate	DM79F6G	Malnutrition	5B50-5B71	Approved	[18]
Calcitriol	DM8ZVJ7	Congenital alopecia	LC30	Approved	[19]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[20]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[21]

Molecular Interaction Atlas of This Drug

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Protein S100-A4 (S100A4)	OTLRGFSQ	S10A4_HUMAN	Gene/Protein Processing	[4]

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: 7443).
• [2] ClinicalTrials.gov (NCT01546571) Study of a Melanoma Vaccine in Stage IIb, IIc, and III Melanoma Patients. U.S. National Institutes of Health.
• [3] The skin cancer chemotherapeutic agent ingenol-3-angelate (PEP005) is a substrate for the epidermal multidrug transporter (ABCB1) and targets tumor vasculature. Cancer Res. 2010 Jun 1;70(11):4509-19.
• [4] Repurposing of ingenol mebutate for treating human colorectal cancer by targeting S100 calcium-binding protein A4 (S100A4). Toxicol Appl Pharmacol. 2022 Aug 15;449:116134. doi: 10.1016/j.taap.2022.116134. Epub 2022 Jun 18.
• [5] Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
• [6] MDR1 (ABCB1) G1199A (Ser400Asn) polymorphism alters transepithelial permeability and sensitivity to anticancer agents. Cancer Chemother Pharmacol. 2009 Jun;64(1):183-8.
• [7] Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
• [8] Folate transporter expression decreases in the human placenta throughout pregnancy and in pre-eclampsia. Pregnancy Hypertens. 2012 Apr;2(2):123-31.
• [9] Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res. 2001 Dec;18(12):1660-8.
• [10] Antiestrogens and steroid hormones: substrates of the human P-glycoprotein. Biochem Pharmacol. 1994 Jul 19;48(2):287-92.
• [11] Association of genetic polymorphisms in the influx transporter SLCO1B3 and the efflux transporter ABCB1 with imatinib pharmacokinetics in patients with chronic myeloid leukemia. Ther Drug Monit. 2011 Apr;33(2):244-50.
• [12] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [13] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [14] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [15] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [16] Arsenic targets Pin1 and cooperates with retinoic acid to inhibit cancer-driving pathways and tumor-initiating cells. Nat Commun. 2018 Aug 9;9(1):3069. doi: 10.1038/s41467-018-05402-2.
• [17] Lunasin, a novel seed peptide, sensitizes human breast cancer MDA-MB-231 cells to aspirin-arrested cell cycle and induced apoptosis. Chem Biol Interact. 2010 Jul 30;186(2):127-34. doi: 10.1016/j.cbi.2010.04.027. Epub 2010 May 21.
• [18] Extracellular ATP drives breast cancer cell migration and metastasis via S100A4 production by cancer cells and fibroblasts. Cancer Lett. 2018 Aug 28;430:1-10. doi: 10.1016/j.canlet.2018.04.043. Epub 2018 May 5.
• [19] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [20] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [21] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.