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

General Information of Drug (ID: DMG65CV)

Drug Name
INCB057643 Drug Info
Synonyms
INCB-057643; 1820889-23-3; UNII-87TZD0JEBS; 87TZD0JEBS; 2,2,4-trimethyl-8-(6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-4-yl)-6-(methylsulfonyl)-2H-benzo[b][1,4]oxazin-3(4H)-one; 2,2,4-Trimethyl-8-(6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo(2,3-C)pyridin-4-yl)-6-(methylsulfonyl)-2H-benzo(b)(1,4)oxazin-3(4H)-one; CHEMBL4594412; SCHEMBL17200525; US9957268, Example 75; BDBM391587; BCP29506; EX-A1908; NSC807398; s8714; NSC-807398; BS-16298; HY-111485; AK00799038; CS-0042192; INCB057643; INCB 057643; CC1(OC2=C(N(C1=O)C)C=C(C=C2C=2C1=C(C(N(C2)C)=O)NC=C1)S(=O)(=O)C)C; 2,2,4-trimethyl-8-(6-methyl-7- oxo-6,7-dihydro-1H- pyrrolo[2,3-c]pyridin-4-yl)-6- (methylsulfonyl)-2H-1,4- benzoxazin-3(4H)-one; 2H-1,4-Benzoxazin-3(4H)-one, 8-(6,7-dihydro-6-methyl-7-oxo-1H-pyrrolo(2,3-C)pyridin-4-yl)-2,2,4-trimethyl-6-(methylsulfonyl)-
Indication
Disease Entry ICD 11 Status REF
Solid tumour/cancer 2A00-2F9Z Phase 1/2 [1]
Cross-matching ID
PubChem CID
118467751
CAS Number
CAS 1820889-23-3
TTD Drug ID
DMG65CV

Molecule-Related Drug Atlas

Molecule-Related Drug Atlas
Molecule Type:
DTT
DOT
Drug Status:
Clinical Trial Drug(s)
Approved Drug(s)
Download the Complete Related Drug List
Drug(s) Targeting Bromodomain and extraterminal domain protein (BET)
Drug Name Drug ID Indication ICD 11 Highest Status REF
CPI-0610 DMPXOYJ Myelofibrosis 2A20.2 Phase 3 [5]
ZEN-3694 DM6VQTF Prostate cancer 2C82.0 Phase 2 [6]
OTX-015 DMI8RG1 Acute myeloid leukaemia 2A60 Phase 1/2 [5]
BMS-986158 DM6LDI4 Solid tumour/cancer 2A00-2F9Z Phase 1/2 [5]
INCB054329 DM7TZL0 Refractory hematologic malignancy 2A85.5 Phase 1/2 [7]
ODM-207 DMOKVJD Solid tumour/cancer 2A00-2F9Z Phase 1/2 [8]
(+)-JQ1 DM1CZSJ Testicular cancer 2C80 Phase 1 [9]
GSK525762 DMPAWBN Haematological malignancy 2B33.Y Phase 1 [5]
PLX51107 DMXLHVW Haematological malignancy 2B33.Y Phase 1 [5]
BI 894999 DM7W5N2 Solid tumour/cancer 2A00-2F9Z Phase 1 [5]
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Drug(s) Affected By Myc proto-oncogene protein (MYC)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Estradiol DMUNTE3 Acne vulgaris ED80 Approved [10]
Sertraline DM0FB1J Coronary heart disease BA80.Z Approved [11]
Fulvestrant DM0YZC6 Breast cancer 2C60-2C65 Approved [12]
Gefitinib DM15F0X Colon adenocarcinoma Approved [13]
Hydrogen peroxide DM1NG5W Infectious disease 1A00-CA43.1 Approved [14]
Selenium DM25CGV N. A. N. A. Approved [15]
Ribavirin DMEYLH9 Hepatitis C virus infection 1E51.1 Approved [16]
Trametinib DM2JGQ3 Melanoma 2C30 Approved [17]
Sulindac DM2QHZU Acute myelogenous leukaemia 2A41 Approved [18]
Methotrexate DM2TEOL Anterior urethra cancer Approved [19]
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Drug(s) Affected By N-myc proto-oncogene protein (MYCN)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Cannabidiol DM0659E Dravet syndrome 8A61.11 Approved [20]
Pantothenic acid DM091H2 Vitamin deficiency 5B55-5B71 Approved [21]
Tretinoin DM49DUI Acne vulgaris ED80 Approved [22]
Isotretinoin DM4QTBN Acne vulgaris ED80 Approved [23]
Panobinostat DM58WKG Chronic graft versus host disease Approved [24]
Arsenic trioxide DM61TA4 Acute lymphoblastic leukaemia 2A85 Approved [25]
LY2835219 DM93VBZ Breast cancer 2C60-2C65 Approved [26]
Valproate DMCFE9I Epilepsy 8A60-8A68 Approved [27]
Emetine DMCT2YF Hepatitis virus infection 1E50-1E51 Approved [4]
Menthol DMG2KW7 Back pain ME84.Z Approved [28]
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Drug(s) Affected By Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Sertraline DM0FB1J Coronary heart disease BA80.Z Approved [29]
Beta-carotene DM0RXBT Vitamin deficiency 5B55-5B71 Approved [30]
Ciprofloxacin XR DM2NLS9 Acute gonococcal cervicitis Approved [31]
Methotrexate DM2TEOL Anterior urethra cancer Approved [32]
Dactinomycin DM2YGNW Adult kidney Wilms tumor Approved [33]
Quercetin DM3NC4M Obesity 5B81 Approved [34]
Penicillamine DM40EF6 Cystinuria 5C60.2 Approved [35]
Tretinoin DM49DUI Acne vulgaris ED80 Approved [30]
Glucosamine DM4ZLFD Osteoarthritis FA00-FA05 Approved [36]
Ethacrynic acid DM60QMR Edema MG29 Approved [37]
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Drug(s) Affected By Serine-protein kinase ATM (ATM)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Cannabidiol DM0659E Dravet syndrome 8A61.11 Approved [38]
Paromomycin DM1AGXN Amoebiasis 1A36 Approved [39]
Hydrogen peroxide DM1NG5W Infectious disease 1A00-CA43.1 Approved [40]
Etretinate DM2CZFA Keratosis ED56 Approved [41]
Quercetin DM3NC4M Obesity 5B81 Approved [34]
Tretinoin DM49DUI Acne vulgaris ED80 Approved [42]
Remdesivir DMBFZ6L Coronavirus Disease 2019 (COVID-19) 1D6Y Approved [43]
Acetic Acid, Glacial DM4SJ5Y infection in the ear canal AA0Y Approved [44]
Rifampicin DM5DSFZ Non-insulin dependent diabetes 5A11 Approved [45]
Arsenic trioxide DM61TA4 Acute lymphoblastic leukaemia 2A85 Approved [46]
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Drug(s) Affected By Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Cannabidiol DM0659E Dravet syndrome 8A61.11 Approved [47]
Hydrogen peroxide DM1NG5W Infectious disease 1A00-CA43.1 Approved [48]
Nitric Oxide DM1RBYG Hypertension BA00-BA04 Approved [49]
Methotrexate DM2TEOL Anterior urethra cancer Approved [50]
Simvastatin DM30SGU Arteriosclerosis BD40 Approved [51]
Quercetin DM3NC4M Obesity 5B81 Approved [52]
Troglitazone DM3VFPD Diabetic complication 5A2Y Approved [53]
Penicillamine DM40EF6 Cystinuria 5C60.2 Approved [35]
Tretinoin DM49DUI Acne vulgaris ED80 Approved [54]
Acetic Acid, Glacial DM4SJ5Y infection in the ear canal AA0Y Approved [44]
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Drug(s) Affected By Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Fulvestrant DM0YZC6 Breast cancer 2C60-2C65 Approved [55]
Marinol DM70IK5 Anorexia nervosa cachexia 6B80 Approved [56]
Valproate DMCFE9I Epilepsy 8A60-8A68 Approved [57]
Ivermectin DMDBX5F Intestinal strongyloidiasis due to nematode parasite 1F6B Approved [58]
Cupric Sulfate DMP0NFQ Fungal infection 1F29-1F2F Approved [59]
Cisplatin DMRHGI9 Adenocarcinoma 2D40 Approved [60]
Arsenic DMTL2Y1 N. A. N. A. Approved [61]
Acetaminophen DMUIE76 Allergic rhinitis CA08.0 Approved [62]
Doxorubicin DMVP5YE Acute myelogenous leukaemia 2A41 Approved [63]
Urethane DM7NSI0 N. A. N. A. Phase 4 [64]
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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
Bromodomain and extraterminal domain protein (BET) TTE4BSY NOUNIPROTAC Inhibitor [2]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) OT2YYI1A MCL1_HUMAN Gene/Protein Processing [3]
Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) OT9G360P IF2B1_HUMAN Gene/Protein Processing [4]
Myc proto-oncogene protein (MYC) OTPV5LUK MYC_HUMAN Gene/Protein Processing [3]
N-myc proto-oncogene protein (MYCN) OTWD33K1 MYCN_HUMAN Gene/Protein Processing [4]
Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1) OTXEE550 APR_HUMAN Gene/Protein Processing [3]
Serine-protein kinase ATM (ATM) OTQVOHLT ATM_HUMAN Post-Translational Modifications [3]
Wee1-like protein kinase OTOHEU0N WEE1_HUMAN Post-Translational Modifications [3]

References

1 ClinicalTrials.gov (NCT02711137) Open-Label Safety and Tolerability Study of INCB057643 in Subjects With Advanced Malignancies. U.S. National Institutes of Health.
2 Development of 2 Bromodomain and Extraterminal Inhibitors With Distinct Pharmacokinetic and Pharmacodynamic Profiles for the Treatment of Advanced Malignancies. Clin Cancer Res. 2020 Mar 15;26(6):1247-1257.
3 The synergy of the XPO1 inhibitors combined with the BET inhibitor INCB057643 in high-grade B-cell lymphoma via downregulation of MYC expression. Sci Rep. 2023 Oct 29;13(1):18554. doi: 10.1038/s41598-023-45721-z.
4 IGF2BP1 induces neuroblastoma via a druggable feedforward loop with MYCN promoting 17q oncogene expression. Mol Cancer. 2023 May 29;22(1):88. doi: 10.1186/s12943-023-01792-0.
5 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
6 Clinical pipeline report, company report or official report of Zenith Epigenetics.
7 The Novel Bromodomain and Extraterminal Domain Inhibitor INCB054329 Induces Vulnerabilities in Myeloma Cells That Inform Rational Combination Strategies. Clin Cancer Res. 2019 Jan 1;25(1):300-311.
8 First-in-human Phase 1 open label study of the BET inhibitor ODM-207 in patients with selected solid tumours. Br J Cancer. 2020 Dec;123(12):1730-1736.
9 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
10 Acetaminophen-induced proliferation of estrogen-responsive breast cancer cells is associated with increases in c-myc RNA expression and NF-kappaB activity. Toxicol Sci. 2002 Apr;66(2):233-43. doi: 10.1093/toxsci/66.2.233.
11 Sertraline induces endoplasmic reticulum stress in hepatic cells. Toxicology. 2014 Aug 1;322:78-88. doi: 10.1016/j.tox.2014.05.007. Epub 2014 May 24.
12 Estrogen regulation in human breast cancer cells of new downstream gene targets involved in estrogen metabolism, cell proliferation and cell transformation. J Mol Endocrinol. 2004 Apr;32(2):397-414.
13 ZD1839 induces p15INK4b and causes G1 arrest by inhibiting the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway. Mol Cancer Ther. 2007 May;6(5):1579-87. doi: 10.1158/1535-7163.MCT-06-0814.
14 Arsenic suppresses gene expression in promyelocytic leukemia cells partly through Sp1 oxidation. Blood. 2005 Jul 1;106(1):304-10.
15 Selenite and selenomethionine promote HL-60 cell cycle progression. J Nutr. 2002 Apr;132(4):674-9. doi: 10.1093/jn/132.4.674.
16 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.
17 Combination small molecule MEK and PI3K inhibition enhances uveal melanoma cell death in a mutant GNAQ- and GNA11-dependent manner. Clin Cancer Res. 2012 Aug 15;18(16):4345-55. doi: 10.1158/1078-0432.CCR-11-3227. Epub 2012 Jun 25.
18 Novel detection and differential utilization of a c-myc transcriptional block in colon cancer chemoprevention. Cancer Res. 2002 Nov 1;62(21):6006-10.
19 The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
20 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.
21 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.
22 All-trans-retinoic acid inhibits collapsin response mediator protein-2 transcriptional activity during SH-SY5Y neuroblastoma cell differentiation. FEBS J. 2007 Jan;274(2):498-511. doi: 10.1111/j.1742-4658.2006.05597.x.
23 Molecular targeting of retinoic acid metabolism in neuroblastoma: the role of the CYP26 inhibitor R116010 in vitro and in vivo. Br J Cancer. 2007 Jun 4;96(11):1675-83.
24 A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
25 [Impact of arsenic trioxide on proliferation and metastasis of drug-resistant human ovarian carcinoma cell line]. Ai Zheng. 2002 Aug;21(8):863-7.
26 Biological specificity of CDK4/6 inhibitors: dose response relationship, in vivo signaling, and composite response signature. Oncotarget. 2017 Jul 4;8(27):43678-43691. doi: 10.18632/oncotarget.18435.
27 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.
28 Repurposing L-menthol for systems medicine and cancer therapeutics? L-menthol induces apoptosis through caspase 10 and by suppressing HSP90. OMICS. 2016 Jan;20(1):53-64.
29 Sertraline, an antidepressant, induces apoptosis in hepatic cells through the mitogen-activated protein kinase pathway. Toxicol Sci. 2014 Feb;137(2):404-15. doi: 10.1093/toxsci/kft254. Epub 2013 Nov 5.
30 Beta-carotene and apocarotenals promote retinoid signaling in BEAS-2B human bronchioepithelial cells. Arch Biochem Biophys. 2006 Nov 1;455(1):48-60.
31 The role of MITF and Mcl-1 proteins in the antiproliferative and proapoptotic effect of ciprofloxacin in amelanotic melanoma cells: In silico and in vitro study. Toxicol In Vitro. 2020 Aug;66:104884. doi: 10.1016/j.tiv.2020.104884. Epub 2020 May 8.
32 Peripheral blood expression of nuclear factor-kappab-regulated genes is associated with rheumatoid arthritis disease activity and responds differentially to anti-tumor necrosis factor-alpha versus methotrexate. J Rheumatol. 2007 Sep;34(9):1817-22. Epub 2007 Aug 1.
33 Quercetin downregulates Mcl-1 by acting on mRNA stability and protein degradation. Br J Cancer. 2011 Jul 12;105(2):221-30. doi: 10.1038/bjc.2011.229.
34 Multifaceted preventive effects of single agent quercetin on a human prostate adenocarcinoma cell line (PC-3): implications for nutritional transcriptomics and multi-target therapy. Med Oncol. 2011 Dec;28(4):1395-404. doi: 10.1007/s12032-010-9603-3. Epub 2010 Jul 2.
35 D-Penicillamine targets metastatic melanoma cells with induction of the unfolded protein response (UPR) and Noxa (PMAIP1)-dependent mitochondrial apoptosis. Apoptosis. 2012 Oct;17(10):1079-94.
36 Anti-cancer properties of glucosamine-hydrochloride in YD-8 human oral cancer cells: Induction of the caspase-dependent apoptosis and down-regulation of HIF-1. Toxicol In Vitro. 2012 Feb;26(1):42-50. doi: 10.1016/j.tiv.2011.10.005. Epub 2011 Oct 13.
37 Ethacrynic acid and a derivative enhance apoptosis in arsenic trioxide-treated myeloid leukemia and lymphoma cells: the role of glutathione S-transferase p1-1. Clin Cancer Res. 2012 Dec 15;18(24):6690-701. doi: 10.1158/1078-0432.CCR-12-0770. Epub 2012 Oct 18.
38 Cannabidiol Induces Cell Cycle Arrest and Cell Apoptosis in Human Gastric Cancer SGC-7901 Cells. Biomolecules. 2019 Jul 25;9(8):302. doi: 10.3390/biom9080302.
39 Correction of ATM gene function by aminoglycoside-induced read-through of premature termination codons. Proc Natl Acad Sci U S A. 2004 Nov 2;101(44):15676-81. doi: 10.1073/pnas.0405155101. Epub 2004 Oct 21.
40 Pro-oxidant induced DNA damage in human lymphoblastoid cells: homeostatic mechanisms of genotoxic tolerance. Toxicol Sci. 2012 Aug;128(2):387-97. doi: 10.1093/toxsci/kfs152. Epub 2012 Apr 26.
41 Bexarotene activates the p53/p73 pathway in human cutaneous T-cell lymphoma. Br J Dermatol. 2009 Mar;160(3):519-26. doi: 10.1111/j.1365-2133.2008.08931.x. Epub 2008 Nov 25.
42 Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
43 An in vitro study on anti-carcinogenic effect of remdesivir in human ovarian cancer cells via generation of reactive oxygen species. Hum Exp Toxicol. 2022 Jan-Dec;41:9603271221089257. doi: 10.1177/09603271221089257.
44 Motexafin gadolinium and zinc induce oxidative stress responses and apoptosis in B-cell lymphoma lines. Cancer Res. 2005 Dec 15;65(24):11676-88.
45 Integrated analysis of rifampicin-induced microRNA and gene expression changes in human hepatocytes. Drug Metab Pharmacokinet. 2014;29(4):333-40.
46 Arsenic trioxide induces apoptosis in NB-4, an acute promyelocytic leukemia cell line, through up-regulation of p73 via suppression of nuclear factor kappa B-mediated inhibition of p73 transcription and prevention of NF-kappaB-mediated induction of XIAP, cIAP2, BCL-XL and survivin. Med Oncol. 2010 Sep;27(3):833-42. doi: 10.1007/s12032-009-9294-9. Epub 2009 Sep 10.
47 Inhibiting Heat Shock Proteins Can Potentiate the Cytotoxic Effect of Cannabidiol in Human Glioma Cells. Anticancer Res. 2015 Nov;35(11):5827-37.
48 Time series analysis of oxidative stress response patterns in HepG2: a toxicogenomics approach. Toxicology. 2013 Apr 5;306:24-34.
49 Apoptotic signaling pathways induced by nitric oxide in human lymphoblastoid cells expressing wild-type or mutant p53. Cancer Res. 2004 May 1;64(9):3022-9. doi: 10.1158/0008-5472.can-03-1880.
50 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.
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53 Adipogenic Effects and Gene Expression Profiling of Firemaster? 550 Components in Human Primary Preadipocytes. Environ Health Perspect. 2017 Sep 14;125(9):097013. doi: 10.1289/EHP1318.
54 Comparison of the gene expression profiles of monocytic versus granulocytic lineages of HL-60 leukemia cell differentiation by DNA microarray analysis. Life Sci. 2003 Aug 15;73(13):1705-19. doi: 10.1016/s0024-3205(03)00515-0.
55 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
56 THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
57 Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
58 Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
59 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
60 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
61 Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
62 Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
63 METTL14 promotes doxorubicin-induced cardiomyocyte ferroptosis by regulating the KCNQ1OT1-miR-7-5p-TFRC axis. Cell Biol Toxicol. 2023 Jun;39(3):1015-1035. doi: 10.1007/s10565-021-09660-7. Epub 2021 Oct 14.
64 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.