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

General Information of Drug (ID: DMPBV9D)

• Drug Name: Flupirtine Drug Info
• Synonyms: Flupirtine; 56995-20-1; Flupirtine [INN:BAN]; Flupirtinum [INN-Latin]; Flupirtino [INN-Spanish]; UNII-MOH3ET196H; C15H17FN4O2; EINECS 260-503-8; MOH3ET196H; JUUFBMODXQKSTD-UHFFFAOYSA-N; ethyl N-[2-amino-6-[(4-fluorophenyl)methylamino]pyridin-3-yl]carbamate; D 9998; flupirtin maleate; ethyl 2-amino-6-(4-fluorobenzylamino)pyridin-3-ylcarbamate; Flupirtinum; Flupirtino; MLS002153180; Carbamic acid, (2-amino-6-(((4-fluorophenyl)methyl)amino)-3-pyridinyl)-, ethyl ester; NCGC00015451-03; SMR001230672; Flupirtin; Carbamic acid, [2-ami

Indication

Disease Entry	ICD 11	Status	REF
Cancer related pain	MG30	Phase 2	[1]
Fibromyalgia	MG30.01	Phase 2	[1]

• Cross-matching ID:
  PubChem CID: 53276
  ChEBI ID: CHEMBL94646
  CAS Number: CAS 56995-20-1
  TTD Drug ID: DMPBV9D

Molecule-Related Drug Atlas

Drug(s) Targeting Voltage-gated potassium channel Kv7 (KCNQ)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Retigabine	DMGNYIH	Behcet disease	4A62	Approved	[5]
CNSB-001	DM2PEU5	Neuropathic pain	8E43.0	Phase 2	[6]
DMP-543	DMCNEOZ	Parkinson disease	8A00.0	Discontinued in Phase 2	[7]

Drug(s) Affected By Bile salt export pump (ABCB11)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Glimepiride	DM5FSJA	Diabetic complication	5A2Y	Approved	[3]
Ezetimibe	DM7A8TW	Atherosclerosis	BD40	Approved	[8]
Glipizide	DMZA5PQ	Diabetic complication	5A2Y	Approved	[8]
Bosentan	DMIOGBU	Pulmonary arterial hypertension	BB01.0	Approved	[9]
Indinavir	DM0T3YH	Human immunodeficiency virus infection	1C62	Approved	[3]
Ofloxacin	DM0VQN3	Acute gonococcal cervicitis		Approved	[8]
Primidone	DM0WX6I	Epilepsy	8A60-8A68	Approved	[10]
Gefitinib	DM15F0X	Colon adenocarcinoma		Approved	[3]
Drospirenone	DM1A9W3	Acne vulgaris	ED80	Approved	[11]
Nitrendipine	DM21C09	Hypertension	BA00-BA04	Approved	[3]

Drug(s) Affected By Cytotoxic granule associated RNA binding protein TIA1 (TIA1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[12]
Selenium	DM25CGV	N. A.	N. A.	Approved	[13]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[14]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[15]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[16]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[17]
Ivermectin	DMDBX5F	Intestinal strongyloidiasis due to nematode parasite	1F6B	Approved	[18]
Temozolomide	DMKECZD	Adenocarcinoma	2D40	Approved	[19]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[20]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[21]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Voltage-gated potassium channel Kv7 (KCNQ)	TTQ29KF	NOUNIPROTAC	Modulator	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Gene/Protein Processing	[3]
Cytotoxic granule associated RNA binding protein TIA1 (TIA1)	OTGPN3P8	TIA1_HUMAN	Gene/Protein Processing	[4]

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: 2598).
• [2] Treatment with the Kv7 potassium channel activator flupirtine is beneficial in two independent mouse models of pulmonary hypertension. Br J Pharmacol. 2009 August; 157(7): 1241-1249.
• [3] Interference with bile salt export pump function is a susceptibility factor for human liver injury in drug development. Toxicol Sci. 2010 Dec; 118(2):485-500.
• [4] Melatonin counteracts ischemia-induced apoptosis in human retinal pigment epithelial cells. Invest Ophthalmol Vis Sci. 1998 Nov;39(12):2374-83.
• [5] Antibodies and venom peptides: new modalities for ion channels. Nat Rev Drug Discov. 2019 May;18(5):339-357.
• [6] The Kv7 potassium channel activator flupirtine affects clinical excitability parameters of myelinated axons in isolated rat sural nerve. J Peripher Nerv Syst. 2010 Mar;15(1):63-72.
• [7] KV7 channels regulate muscle tone and nonadrenergic noncholinergic relaxation of the rat gastric fundus.Pharmacol Res.2011 Oct;64(4):397-409.
• [8] Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11). Toxicol Sci. 2013 Dec;136(2):328-43.
• [9] Omics-based responses induced by bosentan in human hepatoma HepaRG cell cultures. Arch Toxicol. 2018 Jun;92(6):1939-1952.
• [10] Evaluating the Role of Multidrug Resistance Protein 3 (MDR3) Inhibition in Predicting Drug-Induced Liver Injury Using 125 Pharmaceuticals. Chem Res Toxicol. 2017 May 15;30(5):1219-1229. doi: 10.1021/acs.chemrestox.7b00048. Epub 2017 May 4.
• [11] A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development. Toxicol Sci. 2013 Nov;136(1):216-41.
• [12] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [13] 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.
• [14] 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.
• [15] Suppression of mammary carcinoma growth by retinoic acid: proapoptotic genes are targets for retinoic acid receptor and cellular retinoic acid-binding protein II signaling. Cancer Res. 2005 Sep 15;65(18):8193-9. doi: 10.1158/0008-5472.CAN-05-1177.
• [16] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [17] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [18] 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.
• [19] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [20] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [21] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.