General Information of Drug (ID: DM4LSNE)

Drug Name
Procaine Drug Info
Synonyms
Allocaine; Anticort; Anuject; Duracaine; Gerokit; Gerovital; Jenacain; Jenacaine; Nissocaine; Norocaine; Novocain; Novocaine; Procain; Procaina; Procainum; Scurocaine; Spinocaine; Solution of novocain; Factor H3; SP01; SP01A; Stoff H3; Vitamin H3; Anticort (TM); Diethylaminoethyl p-aminobenzoate; Gerovital H-3; Novocain (TN); P-Aminobenzoyldiethylaminoethanol; P-Aminobenzyoyldiethylaminoethanol; Procaina [INN-Spanish]; Procaine (INN); Procaine [INN:BAN]; Procaine, base; Procainum [INN-Latin]; SP-01A; Solution of novocain (TN); Beta-Diethylaminoethyl 4-aminobenzoate; P-Aminobenzoic acid 2-diethylaminoethyl ester; Beta-(Diethylamino)ethyl 4-aminobenzoate; Beta-(Diethylamino)ethyl p-aminobenzoate; BENZOIC ACID,4-AMINO,2-DIETHYLAMINOETHYL ESTER PROCAIN BASE; Benzoic acid, 4-amino-, 2-(diethylamino)ethyl ester; Benzoic acid, p-amino-, 2-(diethylamino)ethyl ester; 2-(Diethylamino)ethyl 4-aminobenzoate; 2-(Diethylamino)ethyl p-aminobenzoate; 2-(Diethylamino)ethyl-4-aminobenzoate; 2-Diethylaminoethyl 4-aminobenzoate; 2-Diethylaminoethyl p-aminobenzoate; 2-Diethylaminoethylester kyseliny p-aminobenzoove; 2-Diethylaminoethylester kyseliny p-aminobenzoove [Czech]; 4-Aminobenzoesaeure-beta-diethylaminoethylester; 4-Aminobenzoic acid 2-(diethylamino) ethyl ester; 4-Aminobenzoic acid diethylaminoethyl ester
Indication
Disease Entry ICD 11 Status REF
Anaesthesia 9A78.6 Approved [1]
Therapeutic Class
Anesthetics
Cross-matching ID
PubChem CID
4914
ChEBI ID
CHEMBL569
CAS Number
CAS 59-46-1
TTD Drug ID
DM4LSNE
ACDINA Drug ID
D01361

Molecule-Related Drug Atlas

Molecule-Related Drug Atlas
Molecule Type:
DTT
DOT
Drug Status:
Approved Drug(s)
Clinical Trial Drug(s)
Discontinued Drug(s)
Preclinical Drug(s)
Drug(s) Targeting 5-HT 3A receptor (HTR3A)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Dolasetron DMMG26Z Nausea MD90 Approved [6]
Alosetron DML2A03 Diarrhea-predominant irritable bowel syndrome DD91.01 Approved [7]
Tropisetron DMNSJ7V Fibromyalgia MG30.01 Approved [8]
Palonosetron DMBHMOX Nausea MD90 Approved [9]
Levetiracetam DMTGDN8 Epilepsy 8A60-8A68 Approved [8]
Cilansetron DMP0NGX Irritable bowel syndrome DD91.0 Phase 3 [10]
BEMESETRON DMSPJX9 N. A. N. A. Discontinued in Phase 3 [11]
Norcisapride DMJSKUI Gastroesophageal reflux disease DA22.Z Discontinued in Phase 2 [12]
YM-114 DML2IXO Nausea MD90 Discontinued in Phase 2 [13]
ATI-17000 DMZJVR5 Irritable bowel syndrome DD91.0 Preclinical [14]
⏷ Show the Full List of 10 Drug(s)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Verapamil DMA7PEW Angina pectoris BA40 Approved [5]
Vidarabine DM0N85H Hepatosplenic T-cell lymphoma Approved [5]
Beta-carotene DM0RXBT Vitamin deficiency 5B55-5B71 Approved [15]
Fulvestrant DM0YZC6 Breast cancer 2C60-2C65 Approved [16]
Secobarbital DM14RF5 Epilepsy 8A60-8A68 Approved [17]
Etidronic acid DM1XHYJ Bone Paget disease Approved [5]
Tiaprofenic acid DM23D7J Osteoarthritis FA00-FA05 Approved [5]
Bromperidol DM24XYQ Schizophrenia 6A20 Approved [5]
Simvastatin DM30SGU Arteriosclerosis BD40 Approved [18]
Deoxycholic acid DM3GYAL Subcutaneous fat disorder EF02 Approved [19]
⏷ Show the Full List of 10 Drug(s)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Cannabidiol DM0659E Dravet syndrome 8A61.11 Approved [20]
Hydrogen peroxide DM1NG5W Infectious disease 1A00-CA43.1 Approved [21]
Acocantherin DM7JT24 Atrial fibrillation BC81.3 Approved [22]
Valproate DMCFE9I Epilepsy 8A60-8A68 Approved [23]
Ivermectin DMDBX5F Intestinal strongyloidiasis due to nematode parasite 1F6B Approved [24]
Diclofenac DMPIHLS Chronic renal failure GB61.Z Approved [25]
Cisplatin DMRHGI9 Adenocarcinoma 2D40 Approved [26]
Arsenic DMTL2Y1 N. A. N. A. Approved [27]
Acetaminophen DMUIE76 Allergic rhinitis CA08.0 Approved [28]
Carbamazepine DMZOLBI Epilepsy 8A60-8A68 Approved [25]
⏷ Show the Full List of 10 Drug(s)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Cisplatin DMRHGI9 Adenocarcinoma 2D40 Approved [29]
Progesterone DMUY35B Amenorrhea GA20.0 Approved [30]
Cannabidiol DM0659E Dravet syndrome 8A61.11 Approved [31]
Sertraline DM0FB1J Coronary heart disease BA80.Z Approved [32]
Beta-carotene DM0RXBT Vitamin deficiency 5B55-5B71 Approved [33]
Fulvestrant DM0YZC6 Breast cancer 2C60-2C65 Approved [34]
Secobarbital DM14RF5 Epilepsy 8A60-8A68 Approved [35]
Gefitinib DM15F0X Colon adenocarcinoma Approved [36]
Fexofenadine DM17ONX Allergic rhinitis CA08.0 Approved [37]
Hydrogen peroxide DM1NG5W Infectious disease 1A00-CA43.1 Approved [38]
⏷ Show the Full List of 10 Drug(s)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Ethanol DMDRQZU Chronic pain MG30 Approved [39]
Progesterone DMUY35B Amenorrhea GA20.0 Approved [30]
Carvedilol DMHTEAO Chronic heart failure BD1Z Approved [40]
Paclitaxel DMLB81S Breast carcinoma Approved [41]
Etoposide DMNH3PG Acute myelogenous leukaemia 2A41 Approved [42]
Cisplatin DMRHGI9 Adenocarcinoma 2D40 Approved [29]
Urokinase DM0GOUD Myocardial infarction BA41-BA43 Approved [43]
Cannabidiol DM0659E Dravet syndrome 8A61.11 Approved [44]
Sertraline DM0FB1J Coronary heart disease BA80.Z Approved [32]
Beta-carotene DM0RXBT Vitamin deficiency 5B55-5B71 Approved [33]
⏷ Show the Full List of 10 Drug(s)
Drug(s) Affected By Cadherin-5 (CDH5)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Hydrogen peroxide DM1NG5W Infectious disease 1A00-CA43.1 Approved [45]
Tretinoin DM49DUI Acne vulgaris ED80 Approved [46]
Isotretinoin DM4QTBN Acne vulgaris ED80 Approved [47]
Valproate DMCFE9I Epilepsy 8A60-8A68 Approved [48]
Ethanol DMDRQZU Chronic pain MG30 Approved [49]
Hydrocortisone DMGEMB7 Acne vulgaris ED80 Approved [50]
Doxorubicin DMVP5YE Acute myelogenous leukaemia 2A41 Approved [51]
Permethrin DMZ0Q1G Pediculus capitis infestation 1G00.0 Approved [52]
Triclosan DMZUR4N Malaria 1F40-1F45 Approved [53]
Resveratrol DM3RWXL Giant cell arteritis 4A44.2 Phase 3 [54]
⏷ Show the Full List of 10 Drug(s)
Drug(s) Affected By Cocaine esterase (CES2)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Dexamethasone DMMWZET Acute adrenal insufficiency Approved [55]
Irinotecan DMP6SC2 Adenocarcinoma 2D40 Approved [56]
Dextropropoxyphene DM23HCX Pain MG30-MG3Z Approved [57]
Methotrexate DM2TEOL Anterior urethra cancer Approved [58]
Quercetin DM3NC4M Obesity 5B81 Approved [59]
Tacrine DM51FY6 Alzheimer disease 8A20 Approved [60]
Rifampicin DM5DSFZ Non-insulin dependent diabetes 5A11 Approved [61]
Ciclosporin DMAZJFX Graft-versus-host disease 4B24 Approved [62]
Testosterone enanthate DMB6871 N. A. N. A. Approved [63]
Cantharidin DMBP5N3 Molluscum contagiosum infection 1E76 Approved [64]
⏷ Show the Full List of 10 Drug(s)

Molecular Interaction Atlas of This Drug

Molecular Interaction Atlas

Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
5-HT 3A receptor (HTR3A) TTPC4TU 5HT3A_HUMAN Antagonist [2]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 (PLCG1) OTSBQR6D PLCG1_HUMAN Post-Translational Modifications [3]
Cadherin-5 (CDH5) OTVX0E1Q CADH5_HUMAN Gene/Protein Processing [3]
Cocaine esterase (CES2) OTC647SQ EST2_HUMAN Biotransformations [4]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Post-Translational Modifications [3]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Post-Translational Modifications [3]
Nuclear receptor subfamily 1 group I member 2 (NR1I2) OTC5U0N5 NR1I2_HUMAN Gene/Protein Processing [5]

References

1 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
2 Local anesthetics have different mechanisms and sites of action at recombinant 5-HT3 receptors. Reg Anesth Pain Med. 2007 Nov-Dec;32(6):462-70.
3 H(1)R mediates local anesthetic-induced vascular permeability in angioedema. Toxicol Appl Pharmacol. 2020 Apr 1;392:114921. doi: 10.1016/j.taap.2020.114921. Epub 2020 Feb 12.
4 Determination and analysis of single nucleotide polymorphisms and haplotype structure of the human carboxylesterase 2 gene. Pharmacogenetics. 2004 Sep;14(9):595-605. doi: 10.1097/00008571-200409000-00004.
5 Screening of a chemical library reveals novel PXR-activating pharmacologic compounds. Toxicol Lett. 2015 Jan 5;232(1):193-202. doi: 10.1016/j.toxlet.2014.10.009. Epub 2014 Oct 16.
6 Palonosetron plus dexamethasone versus granisetron plus dexamethasone for prevention of nausea and vomiting during chemotherapy: a double-blind, do... Lancet Oncol. 2009 Feb;10(2):115-24.
7 Efficacy of 5-HT3 antagonists and 5-HT4 agonists in irritable bowel syndrome: systematic review and meta-analysis. Am J Gastroenterol. 2009 Jul;104(7):1831-43; quiz 1844.
8 Emerging therapies for fibromyalgia. Expert Opin Emerg Drugs. 2008 Mar;13(1):53-62.
9 Management of postoperative nausea and vomiting: focus on palonosetron. Ther Clin Risk Manag. 2009 Feb;5(1):21-34.
10 Cilansetron: a new serotonergic agent for the irritable bowel syndrome with diarrhoea.Expert Opin Investig Drugs.2005 Feb;14(2):185-93.
11 Zatosetron, a potent, selective, and long-acting 5HT3 receptor antagonist: synthesis and structure-activity relationships. J Med Chem. 1992 Jan 24;35(2):310-9.
12 mu-Opioid/5-HT4 dual pharmacologically active agents-efforts towards an effective opioid analgesic with less GI and respiratory side effects (Part I). Bioorg Med Chem Lett. 2009 Oct 1;19(19):5679-83.
13 Effect of serotonin (5-HT)3-receptor antagonists YM060, YM114 (KAE-393), ondansetron and granisetron on 5-HT4 receptors and gastric emptying in rodents. Jpn J Pharmacol. 1995 Nov;69(3):205-14.
14 Emerging drugs for irritable bowel syndrome. Expert Opin Emerg Drugs. 2006 May;11(2):293-313.
15 Induction of PXR-mediated metabolism by beta-carotene. Biochim Biophys Acta. 2005 May 30;1740(2):162-9. doi: 10.1016/j.bbadis.2004.11.013. Epub 2004 Dec 8.
16 Lignans, bacteriocides and organochlorine compounds activate the human pregnane X receptor (PXR). Toxicol Appl Pharmacol. 2005 Dec 1;209(2):123-33. doi: 10.1016/j.taap.2005.03.015.
17 Identification and validation of novel human pregnane X receptor activators among prescribed drugs via ligand-based virtual screening. Drug Metab Dispos. 2011 Feb;39(2):337-44. doi: 10.1124/dmd.110.035808. Epub 2010 Nov 10.
18 Identification of HMG-CoA reductase inhibitors as activators for human, mouse and rat constitutive androstane receptor. Drug Metab Dispos. 2005 Jul;33(7):924-9.
19 Acetylated deoxycholic (DCA) and cholic (CA) acids are potent ligands of pregnane X (PXR) receptor. Toxicol Lett. 2017 Jan 4;265:86-96.
20 Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
21 Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
22 Ouabain impairs cell migration, and invasion and alters gene expression of human osteosarcoma U-2 OS cells. Environ Toxicol. 2017 Nov;32(11):2400-2413. doi: 10.1002/tox.22453. Epub 2017 Aug 10.
23 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.
24 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.
25 Drug-induced endoplasmic reticulum and oxidative stress responses independently sensitize toward TNF-mediated hepatotoxicity. Toxicol Sci. 2014 Jul;140(1):144-59. doi: 10.1093/toxsci/kfu072. Epub 2014 Apr 20.
26 Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
27 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.
28 Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
29 Treatment with anticancer agents induces dysregulation of specific Wnt signaling pathways in human ovarian luteinized granulosa cells in vitro. Toxicol Sci. 2013 Nov;136(1):183-92. doi: 10.1093/toxsci/kft175. Epub 2013 Aug 16.
30 Progesterone increases csk homologous kinase in HMC-1560 human mast cells and reduces cell proliferation. J Cell Biochem. 2007 Dec 1;102(5):1271-80. doi: 10.1002/jcb.21357.
31 Cannabidiol upregulates melanogenesis through CB1 dependent pathway by activating p38 MAPK and p42/44 MAPK. Chem Biol Interact. 2017 Aug 1;273:107-114. doi: 10.1016/j.cbi.2017.06.005. Epub 2017 Jun 7.
32 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.
33 Growth stimulation of human pulmonary adenocarcinoma cells and small airway epithelial cells by beta-carotene via activation of cAMP, PKA, CREB and ERK1/2. Int J Cancer. 2006 Mar 15;118(6):1370-80. doi: 10.1002/ijc.21537.
34 Estrogen and pure antiestrogen fulvestrant (ICI 182 780) augment cell-matrigel adhesion of MCF-7 breast cancer cells through a novel G protein coupled estrogen receptor (GPR30)-to-calpain signaling axis. Toxicol Appl Pharmacol. 2014 Mar 1;275(2):176-81. doi: 10.1016/j.taap.2014.01.005. Epub 2014 Jan 17.
35 Inhibition of activator protein 1 by barbiturates is mediated by differential effects on mitogen-activated protein kinases and the small G proteins ras and rac-1. J Pharmacol Exp Ther. 2004 Dec;311(3):1232-40. doi: 10.1124/jpet.104.071332. Epub 2004 Jul 19.
36 Growth of hormone-dependent MCF-7 breast cancer cells is promoted by constitutive caveolin-1 whose expression is lost in an EGF-R-mediated manner during development of tamoxifen resistance. Breast Cancer Res Treat. 2010 Feb;119(3):575-91. doi: 10.1007/s10549-009-0355-8. Epub 2009 Mar 15.
37 Effect of histamine H1 receptor antagonists on TARC/CCL17 and MDC/CCL22 production from CD14+ cells induced by antigenic stimulation in vitro. Int Arch Allergy Immunol. 2011;155(1):38-51. doi: 10.1159/000318720. Epub 2010 Nov 25.
38 SIRT3 Mediates the Antioxidant Effect of Hydrogen Sulfide in Endothelial Cells. Antioxid Redox Signal. 2016 Feb 20;24(6):329-43. doi: 10.1089/ars.2015.6331. Epub 2015 Nov 10.
39 Downregulation of mitogen-activated protein kinases (MAPKs) in chronic ethanol-induced fatty liver. Toxicol Mech Methods. 2020 Jul;30(6):407-416. doi: 10.1080/15376516.2020.1747126. Epub 2020 Apr 1.
40 A unique mechanism of beta-blocker action: carvedilol stimulates beta-arrestin signaling. Proc Natl Acad Sci U S A. 2007 Oct 16;104(42):16657-62. doi: 10.1073/pnas.0707936104. Epub 2007 Oct 9.
41 The stent-eluting drugs sirolimus and paclitaxel suppress healing of the endothelium by induction of autophagy. Am J Pathol. 2009 Nov;175(5):2226-34.
42 Modulation of apoptosis in HaCaT keratinocytes via differential regulation of ERK signaling pathway by flavonoids. J Biol Chem. 2005 Sep 9;280(36):31498-507. doi: 10.1074/jbc.M505537200. Epub 2005 Jul 13.
43 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.
44 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.
45 Disruption of endothelial adherens junction by invasive breast cancer cells is mediated by reactive oxygen species and is attenuated by AHCC. Life Sci. 2013 Dec 18;93(25-26):994-1003. doi: 10.1016/j.lfs.2013.10.027. Epub 2013 Nov 6.
46 Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
47 Gene microarray analysis of human renal cell carcinoma: the effects of HDAC inhibition and retinoid treatment. Cancer Biol Ther. 2008 Oct;7(10):1607-18.
48 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.
49 Ethanol disrupts vascular endothelial barrier: implication in cancer metastasis. Toxicol Sci. 2012 May;127(1):42-53. doi: 10.1093/toxsci/kfs087. Epub 2012 Feb 13.
50 Hydrocortisone enhances the barrier properties of HBMEC/ci, a brain microvascular endothelial cell line, through mesenchymal-to-endothelial transition-like effects. Fluids Barriers CNS. 2015 Mar 5;12:7. doi: 10.1186/s12987-015-0003-0. eCollection 2015.
51 Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
52 Chlorpyrifos, permethrin and cyfluthrin effect on cell survival, permeability, and tight junction in an in-vitro model of the human blood-brain barrier (BBB). Neurotoxicology. 2022 Dec;93:152-162. doi: 10.1016/j.neuro.2022.09.010. Epub 2022 Sep 24.
53 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
54 Inhibition of vascular endothelial growth factor-induced angiogenesis by resveratrol through interruption of Src-dependent vascular endothelial cadherin tyrosine phosphorylation. Mol Pharmacol. 2003 Nov;64(5):1029-36. doi: 10.1124/mol.64.5.1029.
55 Dexamethasone differentially regulates expression of carboxylesterase genes in humans and rats. Drug Metab Dispos. 2000 Feb;28(2):186-91.
56 Transcriptional activation of the carboxylesterase 2 gene by the p53 pathway. Cancer Biol Ther. 2006 Nov;5(11):1450-6.
57 Binding and hydrolysis of meperidine by human liver carboxylesterase hCE-1. J Pharmacol Exp Ther. 1999 Jul;290(1):314-8.
58 Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
59 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.
60 Inhibition of human carboxylesterases hCE1 and hiCE by cholinesterase inhibitors. Chem Biol Interact. 2013 Mar 25;203(1):226-30.
61 Photochemotherapeutic agent 8-methoxypsoralen induces cytochrome P450 3A4 and carboxylesterase HCE2: evidence on an involvement of the pregnane X receptor. Toxicol Sci. 2007 Jan;95(1):13-22.
62 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.
63 Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
64 Hepatoxicity mechanism of cantharidin-induced liver LO2 cells by LC-MS metabolomics combined traditional approaches. Toxicol Lett. 2020 Oct 15;333:49-61. doi: 10.1016/j.toxlet.2020.07.024. Epub 2020 Jul 26.