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

General Information of Drug (ID: DMA14PR)

• Drug Name: TPCA-1 Drug Info
• Synonyms: TPCA1

Indication

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

• Cross-matching ID:
  PubChem CID: 9903786
  ChEBI ID: CHEBI:91403
  CAS Number: CAS 507475-17-4
  TTD Drug ID: DMA14PR

Molecule-Related Drug Atlas

Drug(s) Targeting Inhibitor of nuclear factor kappa-B kinase (IKK)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dihydrothieno [2,3-e]indazole derivative 1	DMUJ3XK	N. A.	N. A.	Patented	[3]
Dihydrothieno [2,3-e]indazole derivative 4	DMR4LPO	N. A.	N. A.	Patented	[3]
Dihydrothieno [2,3-e]indazole derivative 3	DM85VQR	N. A.	N. A.	Patented	[3]
Dihydrothieno [2,3-e]indazole derivative 2	DM0D3HU	N. A.	N. A.	Patented	[3]
PMID23099093C17d	DMWS7O9	Discovery agent	N.A.	Investigative	[4]
Arsenite	DMBCO4Q	Discovery agent	N.A.	Investigative	[5]
5-Bromo-6-methoxy-9H-beta-carboline	DM157OQ	Discovery agent	N.A.	Investigative	[6]
MRT67307	DMYRCHG	Discovery agent	N.A.	Investigative	[7]
PS-1145	DMVUMWZ	Multiple myeloma	2A83	Investigative	[8]
4-hydroxy-2-nonenal	DM2LJFZ	Discovery agent	N.A.	Investigative	[9]

Drug(s) Affected By Inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Colchicine	DM2POTE	Acute gout flare	FA25.0	Approved	[10]
Sulindac	DM2QHZU	Acute myelogenous leukaemia	2A41	Approved	[11]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[12]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[13]
Vinblastine	DM5TVS3	Advanced cancer	2A00-2F9Z	Approved	[10]
Aspirin	DM672AH	Acute coronary syndrome	BA41	Approved	[14]
Testosterone	DM7HUNW	Hot flushes	GA30	Approved	[15]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[16]
Ibrutinib	DMHZCPO	Mantle cell lymphoma	2A85.5	Approved	[17]
Sulfasalazine	DMICA9H	Irritable bowel syndrome	DD91.0	Approved	[18]

Drug(s) Affected By Signal transducer and activator of transcription 3 (STAT3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dexamethasone	DMMWZET	Acute adrenal insufficiency		Approved	[19]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[20]
Sertraline	DM0FB1J	Coronary heart disease	BA80.Z	Approved	[21]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[22]
Trametinib	DM2JGQ3	Melanoma	2C30	Approved	[23]
Sulindac	DM2QHZU	Acute myelogenous leukaemia	2A41	Approved	[24]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[25]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[26]
Cladribine	DM3JDRP	Hairy cell leukaemia	2A82.2	Approved	[27]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[28]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Inhibitor of nuclear factor kappa-B kinase (IKK)	TTRPDBG	NOUNIPROTAC	Inhibitor	[1]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB)	OT9RDS3H	IKKB_HUMAN	Gene/Protein Processing	[2]
Signal transducer and activator of transcription 3 (STAT3)	OTAAGKYZ	STAT3_HUMAN	Gene/Protein Processing	[2]

References

• [1] Attenuation of murine collagen-induced arthritis by a novel, potent, selective small molecule inhibitor of IkappaB Kinase 2, TPCA-1 (2-[(aminocarbo... J Pharmacol Exp Ther. 2005 Jan;312(1):373-81.
• [2] Synergistic induction of IL-6 production in human bronchial epithelial cells in vitro by nickel nanoparticles and lipopolysaccharide is mediated by STAT3 and C/EBP. Toxicol In Vitro. 2022 Sep;83:105394. doi: 10.1016/j.tiv.2022.105394. Epub 2022 May 25.
• [3] Novel NF-B inhibitors: a patent review (2011 - 2014).Expert Opin Ther Pat. 2015 Mar;25(3):319-34.
• [4] Synthesis and structure-activity relationships of a novel series of pyrimidines as potent inhibitors of TBK1/IKKepsilon kinases. Bioorg Med Chem Lett. 2012 Dec 1;22(23):7169-73.
• [5] Inhibition of NF-kappa B activation by arsenite through reaction with a critical cysteine in the activation loop of Ikappa B kinase. J Biol Chem. 2000 Nov 17;275(46):36062-6.
• [6] Novel IKK inhibitors: beta-carbolines. Bioorg Med Chem Lett. 2003 Jul 21;13(14):2419-22.
• [7] Novel cross-talk within the IKK family controls innate immunity. Biochem J. 2011 Feb 15;434(1):93-104.
• [8] Emerging therapies for multiple myeloma. Expert Opin Emerg Drugs. 2009 Mar;14(1):99-127.
• [9] IkappaB kinase, a molecular target for inhibition by 4-hydroxy-2-nonenal. J Biol Chem. 2001 May 25;276(21):18223-8.
• [10] Microtubules are required for NF-kappaB nuclear translocation in neuroblastoma IMR-32 cells: modulation by zinc. J Neurochem. 2006 Oct;99(2):402-15. doi: 10.1111/j.1471-4159.2006.04005.x.
• [11] Sulindac induces apoptotic cell death in susceptible human breast cancer cells through, at least in part, inhibition of IKKbeta. Apoptosis. 2009 Jul;14(7):913-22. doi: 10.1007/s10495-009-0367-1.
• [12] Simvastatin potentiates TNF-alpha-induced apoptosis through the down-regulation of NF-kappaB-dependent antiapoptotic gene products: role of IkappaBalpha kinase and TGF-beta-activated kinase-1. J Immunol. 2007 Feb 15;178(4):2507-16. doi: 10.4049/jimmunol.178.4.2507.
• [13] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [14] Pretreatment of acetylsalicylic acid promotes tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis by down-regulating BCL-2 gene expression. J Biol Chem. 2005 Dec 9;280(49):41047-56. doi: 10.1074/jbc.M503713200. Epub 2005 Sep 30.
• [15] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [16] 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.
• [17] Blockade of oncogenic IB kinase activity in diffuse large B-cell lymphoma by bromodomain and extraterminal domain protein inhibitors. Proc Natl Acad Sci U S A. 2014 Aug 5;111(31):11365-70. doi: 10.1073/pnas.1411701111. Epub 2014 Jul 21.
• [18] Sulfasalazine and BAY 11-7082 interfere with the nuclear factor-kappa B and I kappa B kinase pathway to regulate the release of proinflammatory cytokines from human adipose tissue and skeletal muscle in vitro. Endocrinology. 2005 Mar;146(3):1491-7. doi: 10.1210/en.2004-0809. Epub 2004 Nov 24.
• [19] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
• [20] Cannabidiol Modulates the Immunophenotype and Inhibits the Activation of the Inflammasome in Human Gingival Mesenchymal Stem Cells. Front Physiol. 2016 Nov 24;7:559. doi: 10.3389/fphys.2016.00559. eCollection 2016.
• [21] Immunomodulatory effect of selective serotonin reuptake inhibitors (SSRIs) on human T lymphocyte function and gene expression. Eur Neuropsychopharmacol. 2007 Dec;17(12):774-80.
• [22] Diesel exhaust particulate-induced activation of Stat3 requires activities of EGFR and Src in airway epithelial cells. Am J Physiol Lung Cell Mol Physiol. 2007 Feb;292(2):L422-9. doi: 10.1152/ajplung.00204.2006. Epub 2006 Oct 6.
• [23] Physapubescin B enhances the sensitivity of gastric cancer cells to trametinib by inhibiting the STAT3 signaling pathway. Toxicol Appl Pharmacol. 2020 Dec 1;408:115273. doi: 10.1016/j.taap.2020.115273. Epub 2020 Oct 6.
• [24] Sulindac induces apoptosis and inhibits tumor growth in vivo in head and neck squamous cell carcinoma. Neoplasia. 2007 Mar;9(3):192-9. doi: 10.1593/neo.06781.
• [25] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [26] Simvastatin acts as an inhibitor of interferon gamma-induced cycloxygenase-2 expression in human THP-1 cells, but not in murine RAW264.7 cells. Biocell. 2009 Aug;33(2):107-14.
• [27] Therapeutic potential of cladribine in combination with STAT3 inhibitor against multiple myeloma. BMC Cancer. 2011 Jun 16;11:255. doi: 10.1186/1471-2407-11-255.
• [28] Quercetin exerts anti-melanoma activities and inhibits STAT3 signaling. Biochem Pharmacol. 2014 Feb 1;87(3):424-34. doi: 10.1016/j.bcp.2013.11.008. Epub 2013 Nov 23.