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

General Information of Drug (ID: DM4FW2E)

Drug Name
LMP400 Drug Info
Synonyms
INDOTECAN; 915303-09-2; UNII-BTA69L5M8D; NSC-724998; BTA69L5M8D; 2,3-dimethoxy-6-(3-morpholinopropyl)-5H-[1,3]dioxolo[4',5':5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione; LMP-400; NSC724998; Indotecan(LMP400); Indotecan (LMP400); CHEMBL216462; SCHEMBL7712572; DTXSID90238613; BCP34018; EX-A3020; Indotecan hydrochloride (LMP-400); ZB1545; SB16793; HY-18351; CS-0007476; LMP400; LMP-400; LMP 400; Q27274872; 3-[(Morpholine)-1-propyl]-5,3-dimethoxy-8,9-meth ylenedioxy-5,11-dioxo-11H-indeno[1,2-c]isoquinoline
Indication
Disease Entry ICD 11 Status REF
Lymphoma 2A80-2A86 Phase 1 [1]
Neoplasm 2A00-2F9Z Phase 1 [1]
Cross-matching ID
PubChem CID
11533060
CAS Number
CAS 915303-09-2
TTD Drug ID
DM4FW2E

Molecule-Related Drug Atlas

Molecule-Related Drug Atlas
Molecule Type:
DTT
DOT
Drug Status:
Approved Drug(s)
Clinical Trial Drug(s)
Download the Complete Related Drug List
Drug(s) Targeting DNA topoisomerase I (TOP1)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Irinotecan DMP6SC2 Adenocarcinoma 2D40 Approved [4]
Topotecan DMP6G8T Central nervous system neoplasm Approved [4]
B-Lactams DMR8YD6 Bacterial infection 1A00-1C4Z Approved [5]
Belotecan hydrocholoride DM3SRJZ Small-cell lung cancer 2C25.Y Approved [6]
Topetecan DMAE6LK Small-cell lung cancer 2C25.Y Approved [7]
Karenitecin DMCRGY4 Lung cancer 2C25.0 Phase 3 [8]
Camptothecin DM6CHNJ Solid tumour/cancer 2A00-2F9Z Phase 3 [9]
Exatecan DMCA7FN Solid tumour/cancer 2A00-2F9Z Phase 3 [10]
Edotecarin DM3ZL7D Gastric adenocarcinoma 2B72 Phase 3 [11]
Rubitecan DMDWU1S Human immunodeficiency virus infection 1C62 Phase 3 [12]
⏷ Show the Full List of 10 Drug(s)
Drug(s) Affected By Serine/threonine-protein kinase Chk1 (CHEK1)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Cannabidiol DM0659E Dravet syndrome 8A61.11 Approved [13]
Hydrogen peroxide DM1NG5W Infectious disease 1A00-CA43.1 Approved [14]
Methotrexate DM2TEOL Anterior urethra cancer Approved [15]
Quercetin DM3NC4M Obesity 5B81 Approved [16]
Furazolidone DM3P6V7 Diarrhea ME05.1 Approved [17]
Troglitazone DM3VFPD Diabetic complication 5A2Y Approved [18]
Tretinoin DM49DUI Acne vulgaris ED80 Approved [19]
Zidovudine DM4KI7O Human immunodeficiency virus infection 1C62 Approved [20]
Arsenic trioxide DM61TA4 Acute lymphoblastic leukaemia 2A85 Approved [21]
Liothyronine DM6IR3P Congenital hypothyroidism Approved [22]
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Drug(s) Affected By Serine/threonine-protein kinase Chk2 (CHEK2)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Floxuridine DM04LR2 Colorectal cancer 2B91.Z Approved [23]
Cannabidiol DM0659E Dravet syndrome 8A61.11 Approved [13]
Hydrogen peroxide DM1NG5W Infectious disease 1A00-CA43.1 Approved [24]
Zidovudine DM4KI7O Human immunodeficiency virus infection 1C62 Approved [20]
Arsenic trioxide DM61TA4 Acute lymphoblastic leukaemia 2A85 Approved [25]
Aspirin DM672AH Acute coronary syndrome BA41 Approved [26]
Testosterone DM7HUNW Hot flushes GA30 Approved [27]
Calcitriol DM8ZVJ7 Congenital alopecia LC30 Approved [27]
Valproate DMCFE9I Epilepsy 8A60-8A68 Approved [28]
Capsaicin DMGMF6V Back pain ME84.Z Approved [29]
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Drug(s) Affected By Histone H2AX (H2AX)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Cannabidiol DM0659E Dravet syndrome 8A61.11 Approved [30]
Hydrogen peroxide DM1NG5W Infectious disease 1A00-CA43.1 Approved [31]
Selenium DM25CGV N. A. N. A. Approved [32]
Ribavirin DMEYLH9 Hepatitis C virus infection 1E51.1 Approved [33]
Etretinate DM2CZFA Keratosis ED56 Approved [34]
Methotrexate DM2TEOL Anterior urethra cancer Approved [35]
Dactinomycin DM2YGNW Adult kidney Wilms tumor Approved [36]
Simvastatin DM30SGU Arteriosclerosis BD40 Approved [37]
Lapatinib DM3BH1Y Breast cancer 2C60-2C65 Approved [38]
Quercetin DM3NC4M Obesity 5B81 Approved [39]
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Drug(s) Affected By Serine/threonine-protein kinase ATR (ATR)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Quercetin DM3NC4M Obesity 5B81 Approved [40]
Acetic Acid, Glacial DM4SJ5Y infection in the ear canal AA0Y Approved [41]
Nefazodone DM4ZS8M Major depressive disorder 6A70.3 Approved [42]
Arsenic trioxide DM61TA4 Acute lymphoblastic leukaemia 2A85 Approved [43]
Aspirin DM672AH Acute coronary syndrome BA41 Approved [44]
Acocantherin DM7JT24 Atrial fibrillation BC81.3 Approved [45]
Valproate DMCFE9I Epilepsy 8A60-8A68 Approved [46]
Motexafin gadolinium DMEJKRF Brain cancer 2A00 Approved [41]
Cupric Sulfate DMP0NFQ Fungal infection 1F29-1F2F Approved [47]
Decitabine DMQL8XJ Acute myelogenous leukaemia 2A41 Approved [48]
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Drug(s) Affected By Cellular tumor antigen p53 (TP53)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Cisplatin DMRHGI9 Adenocarcinoma 2D40 Approved [49]
Methotrexate DM2TEOL Anterior urethra cancer Approved [50]
Zidovudine DM4KI7O Human immunodeficiency virus infection 1C62 Approved [51]
Arsenic trioxide DM61TA4 Acute lymphoblastic leukaemia 2A85 Approved [52]
Cidofovir DMA13GD Cytomegalovirus infection 1D82 Approved [53]
Paclitaxel DMLB81S Breast carcinoma Approved [54]
Floxuridine DM04LR2 Colorectal cancer 2B91.Z Approved [55]
Cannabidiol DM0659E Dravet syndrome 8A61.11 Approved [56]
Mechlorethamine DM0CVXA Chronic myelogenous leukaemia 2A20.0 Approved [57]
Fulvestrant DM0YZC6 Breast cancer 2C60-2C65 Approved [58]
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Molecular Interaction Atlas of This Drug

Molecular Interaction Atlas
Download the Complete Interaction Atlas for Visualization in Cytoscape

Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
DNA topoisomerase I (TOP1) TTGTQHC TOP1_HUMAN Inhibitor [2]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Drug Response [3]
Histone H2AX (H2AX) OT18UX57 H2AX_HUMAN Gene/Protein Processing [3]
Serine/threonine-protein kinase ATR (ATR) OTH0OP1J ATR_HUMAN Drug Response [3]
Serine/threonine-protein kinase Chk1 (CHEK1) OTTTI622 CHK1_HUMAN Gene/Protein Processing [3]
Serine/threonine-protein kinase Chk2 (CHEK2) OT8ZPCNS CHK2_HUMAN Gene/Protein Processing [3]

References

1 ClinicalTrials.gov (NCT01794104) Indenoisoquinoline LMP400 for Advanced Solid Tumors and Lymphomas. U.S. National Institutes of Health.
2 Targeting Topoisomerase I in the Era of Precision Medicine. Clin Cancer Res. 2019 Nov 15;25(22):6581-6589.
3 ATR inhibitors VE-821 and VX-970 sensitize cancer cells to topoisomerase i inhibitors by disabling DNA replication initiation and fork elongation responses. Cancer Res. 2014 Dec 1;74(23):6968-79.
4 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
5 Luteolin, an emerging anti-cancer flavonoid, poisons eukaryotic DNA topoisomerase I. Biochem J. 2002 Sep 1;366(Pt 2):653-61.
6 Impact of natural products on developing new anti-cancer agents. Chem Rev. 2009 Jul;109(7):3012-43.
7 Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
8 Characterization of protein kinase chk1 essential for the cell cycle checkpoint after exposure of human head and neck carcinoma A253 cells to a novel topoisomerase I inhibitor BNP1350. Mol Pharmacol.2000 Mar;57(3):453-9.
9 Topoisomerase I inhibitors: camptothecins and beyond. Nat Rev Cancer. 2006 Oct;6(10):789-802.
10 Phase I study of topoisomerase I inhibitor exatecan mesylate (DX-8951f) given as weekly 24-hour infusions three of every four weeks. Clin Cancer Res. 2001 Dec;7(12):3963-70.
11 Edotecarin: a novel topoisomerase I inhibitor. Clin Colorectal Cancer. 2005 May;5(1):27-36.
12 Rubitecan. Expert Opin Investig Drugs. 2006 Jan;15(1):71-9.
13 Cannabidiol-induced transcriptomic changes and cellular senescence in human Sertoli cells. Toxicol Sci. 2023 Feb 17;191(2):227-238. doi: 10.1093/toxsci/kfac131.
14 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.
15 Melanoma coordinates general and cell-specific mechanisms to promote methotrexate resistance. Exp Cell Res. 2012 Jun 10;318(10):1146-59.
16 Quercetin potentiates apoptosis by inhibiting nuclear factor-kappaB signaling in H460 lung cancer cells. Biol Pharm Bull. 2013;36(6):944-51. doi: 10.1248/bpb.b12-01004.
17 Involvement of the activation of Nrf2/HO-1, p38 MAPK signaling pathways and endoplasmic reticulum stress in furazolidone induced cytotoxicity and S phase arrest in human hepatocyte L02 cells: modulation of curcumin. Toxicol Mech Methods. 2017 Mar;27(3):165-172. doi: 10.1080/15376516.2016.1273424. Epub 2017 Jan 8.
18 Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
19 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.
20 Long-term exposure to zidovudine delays cell cycle progression, induces apoptosis, and decreases telomerase activity in human hepatocytes. Toxicol Sci. 2009 Sep;111(1):120-30. doi: 10.1093/toxsci/kfp136. Epub 2009 Jun 18.
21 ATR, PML, and CHK2 play a role in arsenic trioxide-induced apoptosis. J Biol Chem. 2006 Sep 29;281(39):28764-71. doi: 10.1074/jbc.M604392200. Epub 2006 Aug 3.
22 Identification of small molecule proliferating cell nuclear antigen (PCNA) inhibitor that disrupts interactions with PIP-box proteins and inhibits DNA replication. J Biol Chem. 2012 Apr 20;287(17):14289-300. doi: 10.1074/jbc.M112.353201. Epub 2012 Mar 1.
23 Checkpoint signaling, base excision repair, and PARP promote survival of colon cancer cells treated with 5-fluorodeoxyuridine but not 5-fluorouracil. PLoS One. 2011;6(12):e28862. doi: 10.1371/journal.pone.0028862. Epub 2011 Dec 15.
24 Direct activation of ATM by resveratrol under oxidizing conditions. PLoS One. 2014 Jun 16;9(6):e97969. doi: 10.1371/journal.pone.0097969. eCollection 2014.
25 Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells. Toxicol Appl Pharmacol. 2012 Jun 1;261(2):204-16.
26 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.
27 Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
28 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.
29 Triggering of transient receptor potential vanilloid type 1 (TRPV1) by capsaicin induces Fas/CD95-mediated apoptosis of urothelial cancer cells in an ATM-dependent manner. Carcinogenesis. 2009 Aug;30(8):1320-9. doi: 10.1093/carcin/bgp138. Epub 2009 Jun 5.
30 Cannabinoids synergize with carfilzomib, reducing multiple myeloma cells viability and migration. Oncotarget. 2016 Nov 22;7(47):77543-77557. doi: 10.18632/oncotarget.12721.
31 Hsa-let-7g miRNA regulates the anti-tumor effects of gastric cancer cells under oxidative stress through the expression of DDR genes. J Toxicol Sci. 2015 Jun;40(3):329-38. doi: 10.2131/jts.40.329.
32 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.
33 Inhibition of cardiomyocyte differentiation of human induced pluripotent stem cells by Ribavirin: Implication for its cardiac developmental toxicity. Toxicology. 2020 Apr 15;435:152422. doi: 10.1016/j.tox.2020.152422. Epub 2020 Feb 26.
34 Synthesis and structure-activity relationships of new antiproliferative and proapoptotic retinoid-related biphenyl-4-yl-acrylic acids. Bioorg Med Chem. 2007 Jul 15;15(14):4863-75. doi: 10.1016/j.bmc.2007.04.057. Epub 2007 May 3.
35 Methotrexate induces apoptosis through p53/p21-dependent pathway and increases E-cadherin expression through downregulation of HDAC/EZH2. Biochem Pharmacol. 2011 Feb 15;81(4):510-7. doi: 10.1016/j.bcp.2010.11.014. Epub 2010 Nov 27.
36 Actinomycin D inhibits the expression of the cystine/glutamate transporter xCT via attenuation of CD133 synthesis in CD133(+) HCC. Chem Biol Interact. 2019 Aug 25;309:108713. doi: 10.1016/j.cbi.2019.06.026. Epub 2019 Jun 19.
37 Simvastatin and purine analogs have a synergic effect on apoptosis of chronic lymphocytic leukemia cells. Ann Hematol. 2010 Nov;89(11):1115-24. doi: 10.1007/s00277-010-0988-z. Epub 2010 May 25.
38 The involvement of hepatic cytochrome P450s in the cytotoxicity of lapatinib. Toxicol Sci. 2023 Dec 21;197(1):69-78. doi: 10.1093/toxsci/kfad099.
39 The isoflavonoids genistein and quercetin activate different stress signaling pathways as shown by analysis of site-specific phosphorylation of ATM, p53 and histone H2AX. DNA Repair (Amst). 2004 Mar 4;3(3):235-44. doi: 10.1016/j.dnarep.2003.10.014.
40 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.
41 Motexafin gadolinium and zinc induce oxidative stress responses and apoptosis in B-cell lymphoma lines. Cancer Res. 2005 Dec 15;65(24):11676-88.
42 Involvement of mitochondrial dysfunction in nefazodone-induced hepatotoxicity. Food Chem Toxicol. 2016 Aug;94:148-58. doi: 10.1016/j.fct.2016.06.001. Epub 2016 Jun 8.
43 Targeting of EGFR increase?anti-cancer effects of arsenic trioxide: Promising treatment for glioblastoma multiform. Eur J Pharmacol. 2018 Feb 5;820:274-285. doi: 10.1016/j.ejphar.2017.12.041. Epub 2017 Dec 20.
44 Aspirin and alterations in DNA repair proteins in the SW480 colorectal cancer cell line. Oncol Rep. 2010 Jul;24(1):37-46. doi: 10.3892/or_00000826.
45 Ouabain induces apoptotic cell death in human prostate DU 145 cancer cells through DNA damage and TRAIL pathways. Environ Toxicol. 2019 Dec;34(12):1329-1339. doi: 10.1002/tox.22834. Epub 2019 Aug 21.
46 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
47 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
48 An ATM- and Rad3-related (ATR) signaling pathway and a phosphorylation-acetylation cascade are involved in activation of p53/p21Waf1/Cip1 in response to 5-aza-2'-deoxycytidine treatment. J Biol Chem. 2008 Feb 1;283(5):2564-74. doi: 10.1074/jbc.M702454200. Epub 2007 Oct 31.
49 p53-R175H mutant gains new function in regulation of doxorubicin-induced apoptosis. Int J Cancer. 2005 Apr 10;114(3):331-6. doi: 10.1002/ijc.20818.
50 The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
51 Azidothymidine and cisplatin increase p14ARF expression in OVCAR-3 ovarian cancer cell line. Toxicol Appl Pharmacol. 2006 Oct 1;216(1):89-97. doi: 10.1016/j.taap.2006.04.015. Epub 2006 May 19.
52 Quantitative analysis of gene expression changes in response to genotoxic compounds. Toxicol In Vitro. 2017 Mar;39:15-28. doi: 10.1016/j.tiv.2016.11.004. Epub 2016 Nov 5.
53 Induction of apoptosis by cidofovir in human papillomavirus (HPV)-positive cells. Oncol Res. 2000;12(9-10):397-408. doi: 10.3727/096504001108747855.
54 Gallic acid potentiates the apoptotic effect of paclitaxel and carboplatin via overexpression of Bax and P53 on the MCF-7 human breast cancer cell line. J Biochem Mol Toxicol. 2021 Feb;35(2):e22638. doi: 10.1002/jbt.22638. Epub 2020 Oct 1.
55 Regulation of human dUTPase gene expression and p53-mediated transcriptional repression in response to oxaliplatin-induced DNA damage. Nucleic Acids Res. 2009 Jan;37(1):78-95. doi: 10.1093/nar/gkn910. Epub 2008 Nov 16.
56 Role of miRNA in the regulation of cannabidiol-mediated apoptosis in neuroblastoma cells. Oncotarget. 2019 Jan 1;10(1):45-59. doi: 10.18632/oncotarget.26534. eCollection 2019 Jan 1.
57 Nitrogen Mustard Alkylates and Cross-Links p53 in Human Keratinocytes. Chem Res Toxicol. 2022 Apr 18;35(4):636-650. doi: 10.1021/acs.chemrestox.1c00420. Epub 2022 Mar 21.
58 Fulvestrant induces resistance by modulating GPER and CDK6 expression: implication of methyltransferases, deacetylases and the hSWI/SNF chromatin remodelling complex. Br J Cancer. 2013 Nov 12;109(10):2751-62. doi: 10.1038/bjc.2013.583. Epub 2013 Oct 29.