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

General Information of Drug (ID: DMDNUM5)

• Drug Name: NU-7432 Drug Info
• Synonyms: NU-7441

Indication

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

• Cross-matching ID:
  PubChem CID: 11327430
  ChEBI ID: CHEBI:91361
  CAS Number: CAS 503468-95-9
  TTD Drug ID: DMDNUM5

Molecule-Related Drug Atlas

Drug(s) Targeting DNA-dependent protein kinase catalytic (PRKDC)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
M3814	DMK2L38	Locally advanced rectal cancer	2B92	Phase 1/2	[3]
AZD7648	DMD9Y5T	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[4]
M9831	DM59TI2	Solid tumour/cancer	2A00-2F9Z	Phase 1	[3]
PP121	DMU8KTO	Discovery agent	N.A.	Investigative	[5]
LY-292223	DML36ZE	Discovery agent	N.A.	Investigative	[6]
Ethyl 1-[(1H-benzimidazol-2(3H)one-5-yl)sulfonyl]-1H-pyrrole-2-carboxylate	DM3FH02	Discovery agent	N.A.	Investigative	[2]
PIK-75	DM9BQTX	Discovery agent	N.A.	Investigative	[7]
KU-0060648	DMQWS6U	Discovery agent	N.A.	Investigative	[8]
ALPHA-NAPHTHOFLAVONE	DMELOIQ	Discovery agent	N.A.	Investigative	[9]
2-Morpholin-4-yl-pyrimido[2,1-a]isoquinolin-4-one	DM79ZOV	Discovery agent	N.A.	Investigative	[9]

Drug(s) Affected By Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[10]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[11]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[12]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[13]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[14]
Adenosine triphosphate	DM79F6G	Malnutrition	5B50-5B71	Approved	[15]
Calcitriol	DM8ZVJ7	Congenital alopecia	LC30	Approved	[16]
Cantharidin	DMBP5N3	Molluscum contagiosum infection	1E76	Approved	[17]
Atorvastatin	DMF28YC	Acute coronary syndrome	BA41	Approved	[18]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[19]

Drug(s) Affected By Serine/threonine-protein kinase mTOR (MTOR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Nicotine	DMWX5CO	Lung cancer	2C25.0	Approved	[20]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[21]
Sertraline	DM0FB1J	Coronary heart disease	BA80.Z	Approved	[22]
Gefitinib	DM15F0X	Colon adenocarcinoma		Approved	[23]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[24]
Ribavirin	DMEYLH9	Hepatitis C virus infection	1E51.1	Approved	[25]
Colchicine	DM2POTE	Acute gout flare	FA25.0	Approved	[26]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[27]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[28]
Hydroquinone	DM6AVR4	Melasma	ED60.1	Approved	[29]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
DNA-dependent protein kinase catalytic (PRKDC)	TTK3PY9	PRKDC_HUMAN	Inhibitor	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA)	OTTOMI8J	PK3CA_HUMAN	Gene/Protein Processing	[2]
Serine/threonine-protein kinase mTOR (MTOR)	OTHH8KU7	MTOR_HUMAN	Gene/Protein Processing	[2]

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: 8010).
• [2] Discovery of potent chromen-4-one inhibitors of the DNA-dependent protein kinase (DNA-PK) using a small-molecule library approach. J Med Chem. 2005 Dec 1;48(24):7829-46.
• [3] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [4] AZD7648 is a potent and selective DNA-PK inhibitor that enhances radiation, chemotherapy and olaparib activity. Nat Commun. 2019 Nov 7;10(1):5065.
• [5] Targeted polypharmacology: discovery of dual inhibitors of tyrosine and phosphoinositide kinases. Nat Chem Biol. 2008 Nov;4(11):691-9.
• [6] Identification of a highly potent and selective DNA-dependent protein kinase (DNA-PK) inhibitor (NU7441) by screening of chromenone libraries. Bioorg Med Chem Lett. 2004 Dec 20;14(24):6083-7.
• [7] A pharmacological map of the PI3-K family defines a role for p110alpha in insulin signaling. Cell. 2006 May 19;125(4):733-47.
• [8] 1-substituted (Dibenzo[b,d]thiophen-4-yl)-2-morpholino-4H-chromen-4-ones endowed with dual DNA-PK/PI3-K inhibitory activity. J Med Chem. 2013 Aug 22;56(16):6386-401.
• [9] Selective benzopyranone and pyrimido[2,1-a]isoquinolin-4-one inhibitors of DNA-dependent protein kinase: synthesis, structure-activity studies, and... J Med Chem. 2005 Jan 27;48(2):569-85.
• [10] 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.
• [11] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [12] 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.
• [13] 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.
• [14] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [15] The identification of 2-(1H-indazol-4-yl)-6-(4-methanesulfonyl-piperazin-1-ylmethyl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidine (GDC-0941) as a potent, selective, orally bioavailable inhibitor of class I PI3 kinase for the treatment of cancer. J Med Chem. 2008 Sep 25;51(18):5522-32. doi: 10.1021/jm800295d.
• [16] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [17] Cantharidin suppresses gastric cancer cell migration/invasion by inhibiting the PI3K/Akt signaling pathway via CCAT1. Chem Biol Interact. 2020 Feb 1;317:108939. doi: 10.1016/j.cbi.2020.108939. Epub 2020 Jan 13.
• [18] Atorvastatin induces MicroRNA-145 expression in HEPG2 cells via regulation of the PI3K/AKT signalling pathway. Chem Biol Interact. 2018 May 1;287:32-40. doi: 10.1016/j.cbi.2018.04.005. Epub 2018 Apr 6.
• [19] 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.
• [20] eIF4E is a critical regulator of human papillomavirus (HPV)-immortalized cervical epithelial (H8) cell growth induced by nicotine. Toxicology. 2019 May 1;419:1-10. doi: 10.1016/j.tox.2019.02.017. Epub 2019 Mar 2.
• [21] Transcriptomic Analysis of Stem Cells Treated with Moringin or Cannabidiol: Analogies and Differences in Inflammation Pathways. Int J Mol Sci. 2019 Nov 30;20(23):6039. doi: 10.3390/ijms20236039.
• [22] Antidepressant drug sertraline modulates AMPK-MTOR signaling-mediated autophagy via targeting mitochondrial VDAC1 protein. Autophagy. 2021 Oct;17(10):2783-2799. doi: 10.1080/15548627.2020.1841953. Epub 2020 Nov 9.
• [23] EGFR tyrosine kinase inhibitors activate autophagy as a cytoprotective response in human lung cancer cells. PLoS One. 2011;6(6):e18691. doi: 10.1371/journal.pone.0018691. Epub 2011 Jun 2.
• [24] Repression of Kisspeptin1 weakens hydrogen peroxide-caused injury in HTR8 cells via adjusting PI3K/AKT/mTOR pathway. J Biochem Mol Toxicol. 2020 May;34(5):e22461. doi: 10.1002/jbt.22461. Epub 2020 Feb 11.
• [25] Ribavirin augments doxorubicin's efficacy in human hepatocellular carcinoma through inhibiting doxorubicin-induced eIF4E activation. J Biochem Mol Toxicol. 2018 Jan;32(1). doi: 10.1002/jbt.22007. Epub 2017 Nov 7.
• [26] Establishment of a 13 genes-based molecular prediction score model to discriminate the neurotoxic potential of food relevant-chemicals. Toxicol Lett. 2022 Feb 1;355:1-18. doi: 10.1016/j.toxlet.2021.10.013. Epub 2021 Nov 5.
• [27] Quercetin inhibits angiogenesis mediated human prostate tumor growth by targeting VEGFR- 2 regulated AKT/mTOR/P70S6K signaling pathways. PLoS One. 2012;7(10):e47516. doi: 10.1371/journal.pone.0047516. Epub 2012 Oct 18.
• [28] A comprehensive analysis of Wnt/beta-catenin signaling pathway-related genes and crosstalk pathways in the treatment of As2O3 in renal cancer. Ren Fail. 2018 Nov;40(1):331-339.
• [29] Hydroquinone-induced endoplasmic reticulum stress affects TK6 cell autophagy and apoptosis via ATF6-mTOR. Environ Toxicol. 2023 Aug;38(8):1874-1890. doi: 10.1002/tox.23814. Epub 2023 May 6.