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

General Information of Drug (ID: DM6BU7N)

• Drug Name: Doramapimod Drug Info
• Synonyms: Doramapimod; 285983-48-4; BIRB-796; BIRB 796; BIRB 796 (Doramapimod); BIRB796; UNII-HO1A8B3YVV; 1-(5-TERT-BUTYL-2-P-TOLYL-2H-PYRAZOL-3-YL)-3-[4-(2-MORPHOLIN-4-YL-ETHOXY)-NAPHTHALEN-1-YL]-UREA; 1-[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea; HO1A8B3YVV; CHEMBL103667; 3-[3-tert-butyl-1-(4-methylphenyl)-1H-pyrazol-5-yl]-1-{4-[2-(morpholin-4-yl)ethoxy]naphthalen-1-yl}urea; CHEBI:40953; MVCOAUNKQVWQHZ-UHFFFAOYSA-N; C31H37N5O3; 1-(3-tert-butyl-1-p-tolyl-1H-pyrazol-5-yl)-3-(4-(2

Indication

Disease Entry	ICD 11	Status	REF
Inflammatory bowel disease	DD72	Discontinued in Phase 2	[1]

• Cross-matching ID:
  PubChem CID: 156422
  ChEBI ID: CHEBI:40953
  CAS Number: CAS 285983-48-4
  TTD Drug ID: DM6BU7N

Molecule-Related Drug Atlas

Drug(s) Targeting Hematopoietic cell kinase (HCK)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BK3	DM6YQO3	N. A.	N. A.	Patented	[5]
3-(6-allyloxy-2-naphthyl)-1-(4-piperidylmethyl)pyrazolo[3,4-d]pyrimidin-4-amine	DM0DYAU	N. A.	N. A.	Patented	[5]
Unii-I92MU0V408	DMUD7H8	N. A.	N. A.	Patented	[2]
US8933228, 3	DMPNCOL	N. A.	N. A.	Patented	[2]
SB19065	DM2MQD0	N. A.	N. A.	Patented	[6]
US9108950, 1	DMPT2ZS	N. A.	N. A.	Patented	[7]
US8933228, Ref 2	DMKEX51	N. A.	N. A.	Patented	[8]
BK7	DMQD4X2	N. A.	N. A.	Patented	[5]
PP121	DMU8KTO	Discovery agent	N.A.	Investigative	[9]
PMID15546730C2	DMOPUIH	Discovery agent	N.A.	Investigative	[10]

Drug(s) Affected By C-X-C motif chemokine 10 (CXCL10)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Nitric Oxide	DM1RBYG	Hypertension	BA00-BA04	Approved	[11]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[12]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[13]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[14]
Isotretinoin	DM4QTBN	Acne vulgaris	ED80	Approved	[15]
Isoniazid	DM5JVS3	Latent tuberculosis infection		Approved	[16]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[17]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[18]
Tofacitinib	DMBS370	Rheumatoid arthritis	FA20	Approved	[19]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[20]

Drug(s) Affected By Mitogen-activated protein kinase 14 (MAPK14)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[21]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[22]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[23]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[24]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[25]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[26]
Chlorpromazine	DMBGZI3	Acute intermittent hepatic porphyria	5C58.11	Approved	[27]
Ethacrynic acid	DM60QMR	Edema	MG29	Approved	[28]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[29]
Aspirin	DM672AH	Acute coronary syndrome	BA41	Approved	[30]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Hematopoietic cell kinase (HCK)	TT42OGM	HCK_HUMAN	Inhibitor	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
C-X-C motif chemokine 10 (CXCL10)	OTTLQ6S0	CXL10_HUMAN	Protein Interaction/Cellular Processes	[3]
Mitogen-activated protein kinase 14 (MAPK14)	OT5TCO3O	MK14_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: 5668).
• [2] Respiratory formulations and compounds for use therein. US8933228.
• [3] The role of IFN-gamma in regulation of IFN-gamma-inducible protein 10 (IP-10) expression in lung epithelial cell and peripheral blood mononuclear cell co-cultures. Respir Res. 2007 Nov 8;8(1):80. doi: 10.1186/1465-9921-8-80.
• [4] Differential effect of p38 and MK2 kinase inhibitors on the inflammatory and toxicity biomarkers in vitro. Hum Exp Toxicol. 2018 May;37(5):521-531. doi: 10.1177/0960327117715901. Epub 2017 Jun 20.
• [5] Compositions and methods for treating toxoplasmosis, cryptosporidiosis, and other apicomplexan protozoan related diseases. US9765037.
• [6] Anti-inflammatory compound having inhibitory activity against multiple tyrosine kinases and pharmaceutical composition containing same. US9062066.
• [7] 1-pyrazolyl-3-(4-((2-anilinopyrimidin-4-yl)oxy)napththalen-1-yl) ureas as p38 MAP kinase inhibitors. US9108950.
• [8] 1-pyrazolyl-3-(4-((2-anilinopyrimidin-4-yl)oxy)napththalen-1-yl) ureas as P38 MAP knase inhibitors. US9724347.
• [9] Targeted polypharmacology: discovery of dual inhibitors of tyrosine and phosphoinositide kinases. Nat Chem Biol. 2008 Nov;4(11):691-9.
• [10] Discovery of novel 2-(aminoheteroaryl)-thiazole-5-carboxamides as potent and orally active Src-family kinase p56(Lck) inhibitors. Bioorg Med Chem Lett. 2004 Dec 20;14(24):6061-6.
• [11] Regulatory role of nitric oxide on monocyte-derived dendritic cell functions. J Interferon Cytokine Res. 2003 Aug;23(8):423-31. doi: 10.1089/107999003322277838.
• [12] Plant polyphenols differentially modulate inflammatory responses of human keratinocytes by interfering with activation of transcription factors NFB and AhR and EGFR-ERK pathway. Toxicol Appl Pharmacol. 2011 Sep 1;255(2):138-49.
• [13] Increased sensitivity for troglitazone-induced cytotoxicity using a human in vitro co-culture model. Toxicol In Vitro. 2009 Oct;23(7):1387-95.
• [14] 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.
• [15] 13-cis retinoic acid inhibits development and progression of chronic allograft nephropathy. Am J Pathol. 2005 Jul;167(1):285-98. doi: 10.1016/S0002-9440(10)62973-2.
• [16] Characterization of drug-specific signaling between primary human hepatocytes and immune cells. Toxicol Sci. 2017 Jul 1;158(1):76-89.
• [17] Gene expression profile induced by arsenic trioxide in chronic lymphocytic leukemia cells reveals a central role for heme oxygenase-1 in apoptosis and regulation of matrix metalloproteinase-9. Oncotarget. 2016 Dec 13;7(50):83359-83377.
• [18] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [19] Regulation of inflammatory responses in tumor necrosis factor-activated and rheumatoid arthritis synovial macrophages by JAK inhibitors. Arthritis Rheum. 2012 Dec;64(12):3856-66. doi: 10.1002/art.37691.
• [20] 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.
• [21] Madecassoside ameliorates cisplatin-induced nephrotoxicity by inhibiting activation of the mitogen activated protein kinase pathway. Environ Toxicol. 2023 Jul;38(7):1473-1483. doi: 10.1002/tox.23777. Epub 2023 Apr 23.
• [22] Gingival Stromal Cells as an In Vitro Model: Cannabidiol Modulates Genes Linked With Amyotrophic Lateral Sclerosis. J Cell Biochem. 2017 Apr;118(4):819-828. doi: 10.1002/jcb.25757. Epub 2016 Nov 28.
• [23] Neuroprotective effects of glucomoringin-isothiocyanate against H(2)O(2)-Induced cytotoxicity in neuroblastoma (SH-SY5Y) cells. Neurotoxicology. 2019 Dec;75:89-104. doi: 10.1016/j.neuro.2019.09.008. Epub 2019 Sep 12.
• [24] Inflammation in methotrexate-induced pulmonary toxicity occurs via the p38 MAPK pathway. Toxicology. 2009 Feb 27;256(3):183-90. doi: 10.1016/j.tox.2008.11.016. Epub 2008 Nov 28.
• [25] Quercetin modulates Nrf2 and glutathione-related defenses in HepG2 cells: Involvement of p38. Chem Biol Interact. 2012 Jan 25;195(2):154-64.
• [26] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [27] Effects of chlorpromazine with and without UV irradiation on gene expression of HepG2 cells. Mutat Res. 2005 Aug 4;575(1-2):47-60. doi: 10.1016/j.mrfmmm.2005.03.002. Epub 2005 Apr 26.
• [28] Characterization of cell death induced by ethacrynic acid in a human colon cancer cell line DLD-1 and suppression by N-acetyl-L-cysteine. Cancer Sci. 2003 Oct;94(10):886-93.
• [29] Arsenic trioxide promotes ERK1/2-mediated phosphorylation and degradation of BIM(EL) to attenuate apoptosis in BEAS-2B cells. Chem Biol Interact. 2023 Jan 5;369:110304. doi: 10.1016/j.cbi.2022.110304. Epub 2022 Dec 10.
• [30] Aspirin-mediated COX-2 transcript stabilization via sustained p38 activation in human intestinal myofibroblasts. Mol Pharmacol. 2004 Feb;65(2):470-8.