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

General Information of Drug (ID: DMW1Y2G)

• Drug Name: Abietic acid Drug Info
• Synonyms: ABIETIC ACID; 514-10-3; Sylvic acid; Abietate; l-Abietic acid; Rosin Acid; 7,13-Abietadien-18-oic acid; Kyselina abietova; Kyselina abietova [Czech]; UNII-V3DHX33184; CCRIS 3183; Abieta-7,13-dien-18-oic acid; Abietic acid, technical; 13-Isopropylpodocarpa-7,13-dien-15-oic acid; EINECS 208-178-3; NSC 25149; Abietinic acid; AI3-17273; CHEBI:28987; V3DHX33184; NSC25149; (-)-Abietic acid; MFCD03423567; Abietic acid, 85%; NCGC00166273-01; 1-Phenanthrenecarboxylic acid, 1,2,3,4,4a,4b,5,6,10,10a-decahydro-1,4a-dimethyl-7-(1-methylethyl)-,

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 10569
  ChEBI ID: CHEBI:28987
  CAS Number: CAS 514-10-3
  TTD Drug ID: DMW1Y2G

Molecule-Related Drug Atlas

Drug(s) Targeting Corticosteroid 11-beta-dehydrogenase 1 (HSD11B1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
GLYCYRRHIZIN	DM8M2N3	Influenza virus infection	1E30-1E32	Phase 3	[3]
BVT.2733	DM6RUKX	Lupus	4A40	Phase 3	[4]
INCB13739	DMLQ3PO	Type-2 diabetes	5A11	Phase 2a	[5]
URSOLIC ACID	DM4SOAW	Metabolic syndrome x	5C50-5D2Z	Phase 2	[6]
JTT-654	DM50M2R	Type-2 diabetes	5A11	Phase 2	[7]
RG-4929	DMT4QRD	Metabolic disorder	5C50-5D2Z	Phase 2	[7]
BMS-770767	DMTVGY7	Hypercholesterolaemia	5C80.0	Phase 2	[7]
UE-2343	DMIERPK	Alzheimer disease	8A20	Phase 2	[8]
AZD-4017	DML9M5S	Ocular hypertension	9C61.01	Phase 2	[7]
Xanamem	DM580GT	Alzheimer disease	8A20	Phase 1/2	[9]

Drug(s) Affected By Interleukin-8 (CXCL8)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Hydrocortisone	DMGEMB7	Acne vulgaris	ED80	Approved	[10]
Nicotine	DMWX5CO	Lung cancer	2C25.0	Approved	[11]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[12]
Pantothenic acid	DM091H2	Vitamin deficiency	5B55-5B71	Approved	[13]
Mechlorethamine	DM0CVXA	Chronic myelogenous leukaemia	2A20.0	Approved	[14]
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[15]
Fexofenadine	DM17ONX	Allergic rhinitis	CA08.0	Approved	[16]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[17]
Nitric Oxide	DM1RBYG	Hypertension	BA00-BA04	Approved	[18]
Lumiracoxib	DM1S4AG	Chronic renal failure	GB61.Z	Approved	[16]

Drug(s) Affected By Cyclic AMP-dependent transcription factor ATF-3 (ATF3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[19]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[20]
Sulindac	DM2QHZU	Acute myelogenous leukaemia	2A41	Approved	[21]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[22]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[23]
Deoxycholic acid	DM3GYAL	Subcutaneous fat disorder	EF02	Approved	[24]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[25]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[26]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[27]
Acetic Acid, Glacial	DM4SJ5Y	infection in the ear canal	AA0Y	Approved	[28]

Drug(s) Affected By Glutamate--cysteine ligase regulatory subunit (GCLM)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[29]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[30]
Clavulanate	DM2FGRT	Bacteremia	1A73	Approved	[31]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[32]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[27]
Isotretinoin	DM4QTBN	Acne vulgaris	ED80	Approved	[33]
Acetic Acid, Glacial	DM4SJ5Y	infection in the ear canal	AA0Y	Approved	[28]
Isoniazid	DM5JVS3	Latent tuberculosis infection		Approved	[34]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[35]
Hydroquinone	DM6AVR4	Melasma	ED60.1	Approved	[2]

Drug(s) Affected By DnaJ homolog subfamily B member 4 (DNAJB4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[19]
Selenium	DM25CGV	N. A.	N. A.	Approved	[36]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[25]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[37]
Cyclophosphamide	DM4O2Z7	Advanced cancer	2A00-2F9Z	Approved	[38]
Acetic Acid, Glacial	DM4SJ5Y	infection in the ear canal	AA0Y	Approved	[28]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[39]
Hydroquinone	DM6AVR4	Melasma	ED60.1	Approved	[2]
Thalidomide	DM70BU5	Adult T-cell leukemia/lymphoma		Approved	[40]
Marinol	DM70IK5	Anorexia nervosa cachexia	6B80	Approved	[19]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Corticosteroid 11-beta-dehydrogenase 1 (HSD11B1)	TTN7BL9	DHI1_HUMAN	Inhibitor	[1]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Cyclic AMP-dependent transcription factor ATF-3 (ATF3)	OTC1UOHP	ATF3_HUMAN	Gene/Protein Processing	[2]
DnaJ homolog subfamily B member 4 (DNAJB4)	OTUD01BK	DNJB4_HUMAN	Gene/Protein Processing	[2]
Glutamate--cysteine ligase regulatory subunit (GCLM)	OT6CP234	GSH0_HUMAN	Gene/Protein Processing	[2]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Gene/Protein Processing	[2]

References

• [1] A rapid screening assay for inhibitors of 11beta-hydroxysteroid dehydrogenases (11beta-HSD): flavanone selectively inhibits 11beta-HSD1 reductase activity. Mol Cell Endocrinol. 2003 Dec 30;212(1-2):41-9.
• [2] An in vitro skin sensitization assay termed EpiSensA for broad sets of chemicals including lipophilic chemicals and pre/pro-haptens. Toxicol In Vitro. 2017 Apr;40:11-25. doi: 10.1016/j.tiv.2016.12.005. Epub 2016 Dec 10.
• [3] Discovery of novel dual functional agent as PPARgamma agonist and 11beta-HSD1 inhibitor for the treatment of diabetes. Bioorg Med Chem. 2009 Aug 1;17(15):5722-32.
• [4] Selective inhibition of 11 beta-hydroxysteroid dehydrogenase type 1 improves hepatic insulin sensitivity in hyperglycemic mice strains. Endocrinology. 2003 Nov;144(11):4755-62.
• [5] Incyte's Selective Oral Inhibitor Of 11beta-HSD1 Demonstrates Improvements In Insulin Sensitivity And Lowers Cholesterol Levels In Type 2 Diabetics. Incyte. 2008.
• [6] 11beta-Hydroxysteroid dehydrogenase 1 inhibiting constituents from Eriobotrya japonica revealed by bioactivity-guided isolation and computational a... Bioorg Med Chem. 2010 Feb 15;18(4):1507-15.
• [7] New Therapeutic Strategies for Type 2 Diabetes: Small Molecule Approaches. 2012. Chapter 5. Page(131).
• [8] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [9] Selection and early clinical evaluation of the brain-penetrant 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) inhibitor UE2343 (Xanamem?). Br J Pharmacol. 2017 Mar;174(5):396-408.
• [10] Monomeric and oligomeric flavanols maintain the endogenous glucocorticoid response in human macrophages in pro-oxidant conditions in vitro. Chem Biol Interact. 2018 Aug 1;291:237-244.
• [11] Nicotine up-regulates IL-8 expression in human gingival epithelial cells following stimulation with IL-1 or P. gingivalis lipopolysaccharide via nicotinic acetylcholine receptor signalling. Arch Oral Biol. 2012 May;57(5):483-90. doi: 10.1016/j.archoralbio.2011.10.007. Epub 2011 Nov 25.
• [12] Ca(2+) Signaling and IL-8 Secretion in Human Testicular Peritubular Cells Involve the Cation Channel TRPV2. Int J Mol Sci. 2018 Sep 19;19(9):2829. doi: 10.3390/ijms19092829.
• [13] Calcium pantothenate modulates gene expression in proliferating human dermal fibroblasts. Exp Dermatol. 2009 Nov;18(11):969-78. doi: 10.1111/j.1600-0625.2009.00884.x. Epub 2009 Apr 8.
• [14] Nitrogen mustard prevents transport of Fra-1 into the nucleus to promote c-Fos- and FosB-dependent IL-8 induction in injured mouse epidermis. Toxicol Lett. 2020 Feb 1;319:256-263. doi: 10.1016/j.toxlet.2019.10.006. Epub 2019 Oct 19.
• [15] ERE-independent ERalpha target genes differentially expressed in human breast tumors. Mol Cell Endocrinol. 2005 Dec 21;245(1-2):53-9. doi: 10.1016/j.mce.2005.10.003. Epub 2005 Nov 17.
• [16] An in vitro coculture system of human peripheral blood mononuclear cells with hepatocellular carcinoma-derived cells for predicting drug-induced liver injury. Arch Toxicol. 2021 Jan;95(1):149-168. doi: 10.1007/s00204-020-02882-4. Epub 2020 Aug 20.
• [17] Gypenosides protect retinal pigment epithelium cells from oxidative stress. Food Chem Toxicol. 2018 Feb;112:76-85.
• [18] Nitric oxide synthase inhibitors attenuate ozone-induced airway inflammation in guinea pigs. Possible role of interleukin-8. Am J Respir Crit Care Med. 2000 Jan;161(1):249-56. doi: 10.1164/ajrccm.161.1.9804096.
• [19] Inhibiting Heat Shock Proteins Can Potentiate the Cytotoxic Effect of Cannabidiol in Human Glioma Cells. Anticancer Res. 2015 Nov;35(11):5827-37.
• [20] Gene expression after treatment with hydrogen peroxide, menadione, or t-butyl hydroperoxide in breast cancer cells. Cancer Res. 2002 Nov 1;62(21):6246-54.
• [21] Expression profile analysis of colon cancer cells in response to sulindac or aspirin. Biochem Biophys Res Commun. 2002 Mar 29;292(2):498-512.
• [22] Development and validation of the TGx-HDACi transcriptomic biomarker to detect histone deacetylase inhibitors in human TK6 cells. Arch Toxicol. 2021 May;95(5):1631-1645. doi: 10.1007/s00204-021-03014-2. Epub 2021 Mar 26.
• [23] Simvastatin inactivates beta1-integrin and extracellular signal-related kinase signaling and inhibits cell proliferation in head and neck squamous cell carcinoma cells. Cancer Sci. 2007 Jun;98(6):890-9.
• [24] Identification of novel activators of the metal responsive transcription factor (MTF-1) using a gene expression biomarker in a microarray compendium. Metallomics. 2020 Sep 23;12(9):1400-1415. doi: 10.1039/d0mt00071j.
• [25] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [26] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [27] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [28] Motexafin gadolinium and zinc induce oxidative stress responses and apoptosis in B-cell lymphoma lines. Cancer Res. 2005 Dec 15;65(24):11676-88.
• [29] Cannabidiol induces antioxidant pathways in keratinocytes by targeting BACH1. Redox Biol. 2020 Jan;28:101321. doi: 10.1016/j.redox.2019.101321. Epub 2019 Sep 5.
• [30] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [31] Molecular mechanisms of hepatotoxic cholestasis by clavulanic acid: Role of NRF2 and FXR pathways. Food Chem Toxicol. 2021 Dec;158:112664. doi: 10.1016/j.fct.2021.112664. Epub 2021 Nov 9.
• [32] Essential role of Nrf2 in keratinocyte protection from UVA by quercetin. Biochem Biophys Res Commun. 2009 Sep 11;387(1):109-14. doi: 10.1016/j.bbrc.2009.06.136. Epub 2009 Jul 1.
• [33] 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.
• [34] Comparison of base-line and chemical-induced transcriptomic responses in HepaRG and RPTEC/TERT1 cells using TempO-Seq. Arch Toxicol. 2018 Aug;92(8):2517-2531.
• [35] Changes in gene expression profiles of multiple myeloma cells induced by arsenic trioxide (ATO): possible mechanisms to explain ATO resistance in vivo. Br J Haematol. 2005 Mar;128(5):636-44.
• [36] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [37] Increased sensitivity for troglitazone-induced cytotoxicity using a human in vitro co-culture model. Toxicol In Vitro. 2009 Oct;23(7):1387-95.
• [38] Transcriptome-based functional classifiers for direct immunotoxicity. Arch Toxicol. 2014 Mar;88(3):673-89.
• [39] Arsenic suppresses gene expression in promyelocytic leukemia cells partly through Sp1 oxidation. Blood. 2005 Jul 1;106(1):304-10.
• [40] Polyunsaturated fatty acids synergize with lipid droplet binding thalidomide analogs to induce oxidative stress in cancer cells. Lipids Health Dis. 2010 Jun 2;9:56. doi: 10.1186/1476-511X-9-56.