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

General Information of Drug (ID: DM92VRP)

• Drug Name: Batimastat Drug Info
• Synonyms: batimastat; 130370-60-4; BB-94; Batimastat (BB-94); BB 94; UNII-BK349F52C9; BB94; Batimastat(BB-94); C23H31N3O4S2; CHEMBL279786; BK349F52C9; Butanediamide, N4-hydroxy-N1-(2-(methylamino)-2-oxo-1-(phenylmethyl)ethyl)-2-(2-methylpropyl)-3-((2-thienylthio)methyl)-, (2R-(1(S*),2R*,3S*))-; 4-(N-HYDROXYAMINO)-2R-ISOBUTYL-2S-(2-THIENYLTHIOMETHYL)SUCCINYL-L-PHENYLALANINE-N-METHYLAMIDE; (2S,3R)-5-Methyl-3-(((alphaS)-alpha-(methylcarbamoyl)phenethyl)carbamoyl)-2-((2-thienylthio)methyl)hexanohydroxamic acid

Indication

Disease Entry	ICD 11	Status	REF
Idiopathic pulmonary fibrosis	CB03.4	Preclinical	[1]

• Cross-matching ID:
  PubChem CID: 5362422
  ChEBI ID: CHEMBL279786
  CAS Number: CAS 130370-60-4
  TTD Drug ID: DM92VRP

Molecule-Related Drug Atlas

Drug(s) Targeting Matrix metalloproteinase-3 (MMP-3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PMID29130358-Compound-Figure10(2a)	DMFWXPS	N. A.	N. A.	Patented	[5]
GM6001	DM7V9CT	Corneal ulcer	9A76	Discontinued in Phase 2	[6]
RS-130830	DMOTANY	Hepatitis C virus infection	1E51.1	Discontinued in Phase 2	[7]
PG-530742	DMELXBQ	Myocardial infarction	BA41-BA43	Discontinued in Phase 2	[8]
SC-44463	DMBPNKT	N. A.	N. A.	Terminated	[9]
BB-1101	DM7GH5Z	Multiple sclerosis	8A40	Terminated	[10]
L-696418	DMV785R	N. A.	N. A.	Terminated	[11]
RO-319790	DML3NEU	Rheumatoid arthritis	FA20	Terminated	[12]
MMI270	DM38N2K	Discovery agent	N.A.	Investigative	[13]
IK-862	DMJA4UE	Discovery agent	N.A.	Investigative	[14]

Drug(s) Affected By Metalloproteinase inhibitor 2 (TIMP2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[15]
Nitric Oxide	DM1RBYG	Hypertension	BA00-BA04	Approved	[16]
Selenium	DM25CGV	N. A.	N. A.	Approved	[17]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[18]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[19]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[20]
Aspirin	DM672AH	Acute coronary syndrome	BA41	Approved	[21]
Calcitriol	DM8ZVJ7	Congenital alopecia	LC30	Approved	[22]
Tetracaine	DM9J6C2	Spinal anesthesia	MB40.3	Approved	[23]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[24]

Drug(s) Affected By Mitogen-activated protein kinase 3 (MAPK3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[25]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[26]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[27]
Sertraline	DM0FB1J	Coronary heart disease	BA80.Z	Approved	[28]
Beta-carotene	DM0RXBT	Vitamin deficiency	5B55-5B71	Approved	[29]
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[30]
Secobarbital	DM14RF5	Epilepsy	8A60-8A68	Approved	[31]
Gefitinib	DM15F0X	Colon adenocarcinoma		Approved	[32]
Fexofenadine	DM17ONX	Allergic rhinitis	CA08.0	Approved	[33]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[34]

Drug(s) Affected By Mitogen-activated protein kinase 1 (MAPK1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ethanol	DMDRQZU	Chronic pain	MG30	Approved	[35]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[26]
Carvedilol	DMHTEAO	Chronic heart failure	BD1Z	Approved	[36]
Paclitaxel	DMLB81S	Breast carcinoma		Approved	[37]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[38]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[25]
Urokinase	DM0GOUD	Myocardial infarction	BA41-BA43	Approved	[39]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[40]
Sertraline	DM0FB1J	Coronary heart disease	BA80.Z	Approved	[28]
Beta-carotene	DM0RXBT	Vitamin deficiency	5B55-5B71	Approved	[29]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Matrix metalloproteinase-3 (MMP-3)	TTUZ2L5	MMP3_HUMAN	Modulator	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Metalloproteinase inhibitor 2 (TIMP2)	OT8S1RRP	TIMP2_HUMAN	Gene/Protein Processing	[3]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Gene/Protein Processing	[4]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Gene/Protein Processing	[4]

References

• [1] Drugs and Targets in Fibrosis. Front Pharmacol. 2017 Nov 23;8:855.
• [2] Matrix metalloproteinase inhibitor BB-94 (batimastat) inhibits human colon tumor growth and spread in a patient-like orthotopic model in nude mice. Cancer Res. 1994 Sep 1;54(17):4726-8.
• [3] Elastin-derived peptides enhance angiogenesis by promoting endothelial cell migration and tubulogenesis through upregulation of MT1-MMP. J Cell Sci. 2005 Jan 15;118(Pt 2):343-56. doi: 10.1242/jcs.01613. Epub 2005 Jan 4.
• [4] Role of EGF receptor ligands in TCDD-induced EGFR down-regulation and cellular proliferation. Chem Biol Interact. 2016 Jun 25;253:38-47. doi: 10.1016/j.cbi.2016.04.031. Epub 2016 Apr 23.
• [5] Gelatinase inhibitors: a patent review (2011-2017).Expert Opin Ther Pat. 2018 Jan;28(1):31-46.
• [6] Introduction of the 4-(4-bromophenyl)benzenesulfonyl group to hydrazide analogs of Ilomastat leads to potent gelatinase B (MMP-9) inhibitors with i... Bioorg Med Chem. 2008 Sep 15;16(18):8745-59.
• [7] Structure-based design of potent and selective inhibitors of collagenase-3 (MMP-13). Bioorg Med Chem Lett. 2005 Feb 15;15(4):1101-6.
• [8] Selective matrix metalloproteinase inhibition attenuates progression of left ventricular dysfunction and remodeling in dogs with chronic heart fail... Am J Physiol Heart Circ Physiol. 2006 Jun;290(6):H2522-7.
• [9] Amide surrogates of matrix metalloproteinase inhibitors: Urea and sulfonamide mimics, Bioorg. Med. Chem. Lett. 7(18):2331-2336 (1997).
• [10] Broad spectrum matrix metalloproteinase inhibitors: an examination of succinamide hydroxamate inhibitors with P1 C alpha gem-disubstitution. Bioorg Med Chem Lett. 1998 Jun 16;8(12):1443-8.
• [11] Inhibition of matrix metalloproteinases by N-carboxyalkyl peptides containing extended alkyl residues At P1', Bioorg. Med. Chem. Lett. 5(6):539-542 (1995).
• [12] The asymmetric synthesis and in vitro characterization of succinyl mercaptoalcohol and mercaptoketone inhibitors of matrix metalloproteinases. Bioorg Med Chem Lett. 1998 May 19;8(10):1163-8.
• [13] Strategies for MMP inhibition in cancer: innovations for the post-trial era. Nat Rev Cancer. 2002 Sep;2(9):657-72.
• [14] Discovery of gamma-lactam hydroxamic acids as selective inhibitors of tumor necrosis factor alpha converting enzyme: design, synthesis, and structu... J Med Chem. 2002 Nov 7;45(23):4954-7.
• [15] 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.
• [16] Gaseous nitrogen oxide promotes human lung cancer cell line A549 migration, invasion, and metastasis via iNOS-mediated MMP-2 production. Toxicol Sci. 2008 Dec;106(2):364-75. doi: 10.1093/toxsci/kfn195. Epub 2008 Sep 16.
• [17] Inhibition of invasion and induction of apoptosis by selenium in human malignant brain tumour cells in vitro. Int J Oncol. 2007 May;30(5):1263-71.
• [18] Integrated assessment by multiple gene expression analysis of quercetin bioactivity on anticancer-related mechanisms in colon cancer cells in vitro. Eur J Nutr. 2005 Mar;44(3):143-56. doi: 10.1007/s00394-004-0503-1. Epub 2004 Apr 30.
• [19] Retinoic acid remodels extracellular matrix (ECM) of cultured human fetal palate mesenchymal cells (hFPMCs) through down-regulation of TGF-/Smad signaling. Toxicol Lett. 2014 Mar 3;225(2):208-15. doi: 10.1016/j.toxlet.2013.12.013. Epub 2013 Dec 24.
• [20] Arsenic trioxide (As2O3) inhibits invasion of HT1080 human fibrosarcoma cells: role of nuclear factor-kappaB and reactive oxygen species. J Cell Biochem. 2005 Aug 1;95(5):955-69. doi: 10.1002/jcb.20452.
• [21] Expression profile analysis of human peripheral blood mononuclear cells in response to aspirin. Arch Immunol Ther Exp (Warsz). 2005 Mar-Apr;53(2):151-8.
• [22] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [23] Tetracaine downregulates matrix metalloproteinase activity and inhibits invasiveness of strongly metastatic MDA-MB-231 human breast cancer cells. Chem Biol Interact. 2023 Nov 1;385:110730. doi: 10.1016/j.cbi.2023.110730. Epub 2023 Oct 7.
• [24] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [25] 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.
• [26] 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.
• [27] 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.
• [28] 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.
• [29] 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.
• [30] 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.
• [31] 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.
• [32] 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.
• [33] 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.
• [34] 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.
• [35] 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.
• [36] 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.
• [37] 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.
• [38] 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.
• [39] 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.
• [40] 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.