PMID-sentid	Pub_year	Sent_text	compound_name	comp_offset	prot_official_name	organism	prot_offset
25869780-8	2015	In addition, flupirtine (10mg/kg and 25mg/kg) treatment alleviated neuronal apoptosis and the reduction of dendritic spine density and synaptophysin expression in the hippocampal CA1 region of CRS mice.	flupirtine	13-23	synaptophysin	Mus musculus	135-148
25869780-9	2015	Furthermore, flupirtine (10mg/kg and 25mg/kg) treatment significantly decreased the expression of Bax and increased the p-Akt and p-GSK-3beta, and flupirtine (25mg/kg) treatment up-regulated the p-Erk1/2 in the hippocampus of CRS mice.	flupirtine	13-23	BCL2-associated X protein	Mus musculus	98-101
25869780-9	2015	Furthermore, flupirtine (10mg/kg and 25mg/kg) treatment significantly decreased the expression of Bax and increased the p-Akt and p-GSK-3beta, and flupirtine (25mg/kg) treatment up-regulated the p-Erk1/2 in the hippocampus of CRS mice.	flupirtine	13-23	thymoma viral proto-oncogene 1	Mus musculus	122-125
25869780-9	2015	Furthermore, flupirtine (10mg/kg and 25mg/kg) treatment significantly decreased the expression of Bax and increased the p-Akt and p-GSK-3beta, and flupirtine (25mg/kg) treatment up-regulated the p-Erk1/2 in the hippocampus of CRS mice.	flupirtine	13-23	glycogen synthase kinase 3 beta	Mus musculus	132-141
25869780-9	2015	Furthermore, flupirtine (10mg/kg and 25mg/kg) treatment significantly decreased the expression of Bax and increased the p-Akt and p-GSK-3beta, and flupirtine (25mg/kg) treatment up-regulated the p-Erk1/2 in the hippocampus of CRS mice.	flupirtine	13-23	mitogen-activated protein kinase 3	Mus musculus	197-203
25869780-10	2015	These results suggested that flupirtine exerted protective effects on the CRS-induced cognitive impairment and hippocampal neuronal apoptosis, which is possibly associated with the activation of Akt/GSK-3beta and Erk1/2 signaling pathways.	flupirtine	29-39	thymoma viral proto-oncogene 1	Mus musculus	195-198
25869780-10	2015	These results suggested that flupirtine exerted protective effects on the CRS-induced cognitive impairment and hippocampal neuronal apoptosis, which is possibly associated with the activation of Akt/GSK-3beta and Erk1/2 signaling pathways.	flupirtine	29-39	glycogen synthase kinase 3 beta	Mus musculus	199-208
25869780-10	2015	These results suggested that flupirtine exerted protective effects on the CRS-induced cognitive impairment and hippocampal neuronal apoptosis, which is possibly associated with the activation of Akt/GSK-3beta and Erk1/2 signaling pathways.	flupirtine	29-39	mitogen-activated protein kinase 3	Mus musculus	213-219
25613539-4	2015	RESULTS: Renal dysfunction led to a relatively small average increase in systemic exposure to flupirtine: on D09, the REN : YN-ratios were 1.37 (95% confidence interval (CI): 1.03-1.82), 1.21 (CI: 1.01-1.45), and 1.34 (CI: 1.09-1.64) for Css,0, Css,max, and Css,av, respectively.	flupirtine	94-104	renin	Homo sapiens	118-121
23394517-6	2013	RESULTS: Flupirtine (3-30 muM) shortened the relative refractory period and increased post-conditioned superexcitability in human myelinated axons in vitro.	flupirtine	9-19	latexin	Homo sapiens	26-29
24120659-6	2013	The KV7 channel activators retigabine and flupirtine concentration-dependently relaxed the taenia coli, with mean EC50s of 19.2 muM and 29.9 muM, respectively.	flupirtine	42-52	latexin	Homo sapiens	128-131
24120659-6	2013	The KV7 channel activators retigabine and flupirtine concentration-dependently relaxed the taenia coli, with mean EC50s of 19.2 muM and 29.9 muM, respectively.	flupirtine	42-52	latexin	Homo sapiens	141-144
23078152-3	2012	This project investigated the synergistic effect of the addition of the potassium channel (KCNQ2-3) modulator flupirtine to morphine treatment in a rat model of prostate cancer-induced bone pain.	flupirtine	110-120	potassium voltage-gated channel subfamily Q member 2	Rattus norvegicus	91-96
21556831-0	2011	Parent-reported benefits of flupirtine in juvenile neuronal ceroid lipofuscinosis (Batten disease; CLN3) are not supported by quantitative data.	flupirtine	28-38	CLN3 lysosomal/endosomal transmembrane protein, battenin	Homo sapiens	42-81
22155095-5	2012	CGRP levels were measured by radioimmunoassay under basal conditions or in the presence of flupirtine, alone or with putative antagonist XE-991.	flupirtine	91-101	calcitonin-related polypeptide alpha	Rattus norvegicus	0-4
22155095-6	2012	We found that flupirtine inhibits in a concentration-dependent manner both basal and capsaicin-stimulated CGRP release from rat brainstem.	flupirtine	14-24	calcitonin-related polypeptide alpha	Rattus norvegicus	106-110
21556831-3	2011	Flupirtine has been shown in vitro to reduce apoptosis in CLN3 lymphocytes.	flupirtine	0-10	CLN3 lysosomal/endosomal transmembrane protein, battenin	Homo sapiens	58-62
21556831-4	2011	Based on that preclinical study, several children with JNCL were given flupirtine by their parents.	flupirtine	71-81	CLN3 lysosomal/endosomal transmembrane protein, battenin	Homo sapiens	55-59
21556831-6	2011	We administered a survey to parents of JNCL children to qualitatively assess flupirtine efficacy.	flupirtine	77-87	CLN3 lysosomal/endosomal transmembrane protein, battenin	Homo sapiens	39-43
21556831-9	2011	Twenty-one percent of survey responders reported administering flupirtine to their JNCL child, and 56% of these families perceived beneficial changes that they attributed to flupirtine.	flupirtine	63-73	CLN3 lysosomal/endosomal transmembrane protein, battenin	Homo sapiens	83-87
22282956-1	2011	A simple, highly sensitive, precise and accurate high-performance liquid chromatographic (LCMSMS) method with mass detection was developed and validated for the rapid quantification of flupirtine (CAS 75507-68-5) in rat plasma samples.	flupirtine	185-195	BCAR1 scaffold protein, Cas family member	Rattus norvegicus	197-200
20885443-4	2011	KCNQ2/3 channel openers N-ethylmaleimide (NEM) and flupirtine caused dose-dependent K(+) efflux, intracellular K(+) depletion, and cell death in hippocampal cultures, whereas little cell death was induced by NEM in cortical cultures.	flupirtine	51-61	potassium voltage-gated channel subfamily KQT member 2	Cricetulus griseus	0-5
18536747-11	2008	Recombinant KCNQ 4 or 5 channels were only activated by retigabine or flupirtine.	flupirtine	70-80	potassium voltage-gated channel, subfamily Q, member 4	Mus musculus	12-18
19508393-7	2009	These effects were attenuated by flupirtine, which also attenuated these indices of PAH in SERT(+) mice.	flupirtine	33-43	solute carrier family 6 (neurotransmitter transporter, serotonin), member 4	Mus musculus	91-95
19508393-8	2009	In the in vitro experiments, flupirtine induced a potent relaxant response in arteries from untreated WT and SERT(+) mice.	flupirtine	29-39	solute carrier family 6 (neurotransmitter transporter, serotonin), member 4	Mus musculus	109-113
19508393-10	2009	CONCLUSIONS AND IMPLICATIONS: Flupirtine significantly attenuated development of chronic hypoxia-induced PAH in mice and reversed established PAH in SERT(+) mice, apparently via K(v)7 channel activation.	flupirtine	30-40	solute carrier family 6 (neurotransmitter transporter, serotonin), member 4	Mus musculus	149-153
19074524-5	2009	With CYP3A1-induced rat liver microsomes an 18% turnover of flupirtine and a 20 to 25% turnover of D13223 took place over 30 min, but less than 5% turnover of flupirtine was observed with all human liver microsomal preparations tested, evidence that cytochrome P450 does not contribute appreciably to the metabolism in humans.	flupirtine	60-70	cytochrome P450, family 3, subfamily a, polypeptide 23-polypeptide 1	Rattus norvegicus	5-11
19074524-7	2009	In contrast, flupirtine was an excellent substrate for both human myeloperoxidase and horse radish peroxidase (HRP).	flupirtine	13-23	myeloperoxidase	Homo sapiens	66-81
18832577-7	2008	Although flupirtine was shown previously to increase neuronal survival by Bcl-2 up-regulation, this mechanism does not appear to play a role in flupirtine-mediated protection of retinal ganglion cells either in vitro or in vivo.	flupirtine	9-19	BCL2 apoptosis regulator	Homo sapiens	74-79
15007119-9	2004	The mean change in ADAS-Cog (baseline to best) was +8.4 (+/-15.3) in the FLU group and +20.6 (+/-15.1) in the PLA group (p = 0.02, one-sided t-test).	flupirtine	73-76	alkylglycerone phosphate synthase	Homo sapiens	19-23
16043230-0	2005	Tumor-necrosis-factor-related apoptosis-inducing-ligand (TRAIL)-mediated death of neurons in living human brain tissue is inhibited by flupirtine-maleate.	flupirtine	135-153	TNF superfamily member 10	Homo sapiens	0-55
16043230-0	2005	Tumor-necrosis-factor-related apoptosis-inducing-ligand (TRAIL)-mediated death of neurons in living human brain tissue is inhibited by flupirtine-maleate.	flupirtine	135-153	TNF superfamily member 10	Homo sapiens	57-62
16043230-3	2005	We observed dose-dependent TRAIL-mediated death of both total human CNS cells and neurons, which was prevented by flupirtine-maleate, a centrally acting analgesic drug with proposed neuroprotective properties.	flupirtine	114-132	TNF superfamily member 10	Homo sapiens	27-32
15488320-9	2004	This effect is most likely due to the hyperpolarization of CA1 pyramidal neurons and the reduction of their input resistance found after application of flupirtine.	flupirtine	152-162	carbonic anhydrase 1	Mus musculus	59-62
11921051-0	2002	Flupirtine blocks apoptosis in batten patient lymphoblasts and in human postmitotic CLN3- and CLN2-deficient neurons.	flupirtine	0-10	CLN3 lysosomal/endosomal transmembrane protein, battenin	Homo sapiens	84-88
11921051-9	2002	Flupirtine upregulates Bcl-2, increases glutathione levels, activates an inwardly rectifying potassium channel, and delays loss of intermitochondrial membrane calcium retention capacity.	flupirtine	0-10	BCL2 apoptosis regulator	Homo sapiens	23-28
9804146-16	1998	The levels of the mRNA transcripts for ICH-1L relative to those for ICH-1S were significantly decreased in cultures treated with 100 microM flupirtine or 100 microM melatonin when compared with levels in control cells.	flupirtine	140-150	caspase 2	Homo sapiens	39-45
11080178-1	2000	The present study investigated the effects of flupirtine (Katadolon) on tumor necrosis factor (TNF)-alpha-mediated cell death and Bcl-2 expression in the permanent rat oligodendrocyte cell line OLN-93 (OLN cells).	flupirtine	58-67	tumor necrosis factor	Rattus norvegicus	72-105
11080178-3	2000	Flupirtine significantly reduced the rate of spontaneous cell death of OLN cells already at low concentrations; TNF-alpha-mediated apoptosis was suppressed only with higher concentrations of flupirtine (100 microM:).	flupirtine	191-201	tumor necrosis factor	Rattus norvegicus	112-121
11080178-7	2000	Furthermore, addition of 10 or 100 microM: flupirtine before incubation with TNF-alpha led to an approximately threefold increase of Bcl-2 expression.	flupirtine	43-53	BCL2, apoptosis regulator	Rattus norvegicus	133-138
11080178-8	2000	Exposure of OLN cells to flupirtine alone moderately augmented the expression of Bcl-2 protein.	flupirtine	25-35	BCL2, apoptosis regulator	Rattus norvegicus	81-86
11080178-9	2000	Our data demonstrate that flupirtine up-regulates the expression of Bcl-2 protein in OLN cells; this Bcl-2 induction is associated with a reduced rate of TNF-alpha-induced cell death.	flupirtine	26-36	BCL2, apoptosis regulator	Rattus norvegicus	68-73
11080178-9	2000	Our data demonstrate that flupirtine up-regulates the expression of Bcl-2 protein in OLN cells; this Bcl-2 induction is associated with a reduced rate of TNF-alpha-induced cell death.	flupirtine	26-36	BCL2, apoptosis regulator	Rattus norvegicus	101-106
11080178-9	2000	Our data demonstrate that flupirtine up-regulates the expression of Bcl-2 protein in OLN cells; this Bcl-2 induction is associated with a reduced rate of TNF-alpha-induced cell death.	flupirtine	26-36	tumor necrosis factor	Rattus norvegicus	154-163
11921051-10	2002	We show that flupirtine aborts etoposide-induced apoptosis in CLN1-, CLN2-, CLN3-, and CLN6-deficient as well as normal lymphoblasts.	flupirtine	13-23	palmitoyl-protein thioesterase 1	Homo sapiens	62-66
11921051-10	2002	We show that flupirtine aborts etoposide-induced apoptosis in CLN1-, CLN2-, CLN3-, and CLN6-deficient as well as normal lymphoblasts.	flupirtine	13-23	tripeptidyl peptidase 1	Homo sapiens	69-73
11921051-10	2002	We show that flupirtine aborts etoposide-induced apoptosis in CLN1-, CLN2-, CLN3-, and CLN6-deficient as well as normal lymphoblasts.	flupirtine	13-23	CLN3 lysosomal/endosomal transmembrane protein, battenin	Homo sapiens	76-80
11921051-11	2002	Flupirtine also prevents the death of CLN3- and CLN2-deficient postmitotic hNT neurons at the mitochondrial level.	flupirtine	0-10	CLN3 lysosomal/endosomal transmembrane protein, battenin	Homo sapiens	38-42
9191602-12	1997	Treatment of RPE cells in serum-free medium with flupirtine (flupirtine gluconate, 100 microM) for 72 hours caused an upregulation of bcl-2 protein.	flupirtine	49-59	BCL2 apoptosis regulator	Homo sapiens	134-139
9191602-13	1997	In contrast, the oncogene proteins for TIAR and ICH-1t, were lower in flupirtine-treated cells than in control cells.	flupirtine	70-80	TIA1 cytotoxic granule associated RNA binding protein like 1	Homo sapiens	39-43
9191602-13	1997	In contrast, the oncogene proteins for TIAR and ICH-1t, were lower in flupirtine-treated cells than in control cells.	flupirtine	70-80	caspase 2	Homo sapiens	48-53
9166730-9	1997	Thus, flupirtine may be adequate for the treatment of the neuronal loss in Alzheimer"s disease (where A beta accumulates in senile plaques) and probably other neurological diseases such as amyotrophic lateral sclerosis.	flupirtine	6-16	amyloid beta precursor protein	Rattus norvegicus	102-108
9134985-12	1997	Neuronal damage in the CA1 sector of the hippocampus and in the striatum produced by 4VO was significantly attenuated with pre-treatment of flupirtine whereas post-treatment did not affect this neuronal damage.	flupirtine	140-150	carbonic anhydrase 1	Rattus norvegicus	23-26
16465210-5	1997	The anti-apoptotic effect of flupirtine was restricted to CD3+ lymphocytes and in particular to CD4+ cells.	flupirtine	29-39	CD4 molecule	Homo sapiens	96-99
8822791-7	1996	Two compounds were found to act cytoprotectively against the deleterious effect caused by gp120 on neurons: Memantine [1-amino-3,5-dimethyladamantane] and Flupirtine [2-amino-3-ethoxycarbonylamino-6-(4-fluoro-benzyl-amino)-pyridine maleate].	flupirtine	155-165	inter-alpha-trypsin inhibitor heavy chain 4	Homo sapiens	90-95
8982732-0	1996	Flupirtine increases the levels of glutathione and Bc1-2 in hNT (human Ntera/D1) neurons: mode of action of the drug-mediated anti-apoptotic effect.	flupirtine	0-10	charged multivesicular body protein 2A	Homo sapiens	51-56
8982732-6	1996	Flupirtine completely abolished this reduction of Bc1-2 and glutathione level at a concentration of 10 microM.	flupirtine	0-10	charged multivesicular body protein 2A	Homo sapiens	50-55
1492848-2	1992	Single oral doses of the non-opioid, centrally-acting analgesic flupirtine maleate (Katadolon, CAS 75507-68-5) were administered to healthy volunteers and the 2 h plasma levels determined with a new specific HPLC assay.	flupirtine	64-82	BCAR1 scaffold protein, Cas family member	Homo sapiens	95-98
30990511-0	2019	Flupirtine and retigabine as templates for ligand-based drug design of KV7.2/3 activators.	flupirtine	0-10	potassium voltage-gated channel subfamily Q member 2	Homo sapiens	71-76
25264565-8	2015	Carriers of variant GSTP1 alleles showed lower bioavailability but increased intestinal secretion of flupirtine and increased efficiency in experimental pain.	flupirtine	101-111	glutathione S-transferase pi 1	Homo sapiens	20-25
35284765-7	2022	This flupirtine analogue showed potent KV7.2/3 opening activity, being six times as active as flupirtine itself, and by design is devoid of the potential for azaquinone diimine formation.	flupirtine	5-15	potassium voltage-gated channel subfamily Q member 2	Homo sapiens	39-46
35201886-6	2022	Disruption of Kcnq2/3 genes in Hcrt neurons of young mice destabilized sleep, mimicking aging-associated sleep fragmentation, whereas the KCNQ-selective activator flupirtine hyperpolarized Hcrt neurons and rejuvenated sleep architecture in aged mice.	flupirtine	163-173	potassium voltage-gated channel, subfamily Q, member 2	Mus musculus	14-21
35201886-6	2022	Disruption of Kcnq2/3 genes in Hcrt neurons of young mice destabilized sleep, mimicking aging-associated sleep fragmentation, whereas the KCNQ-selective activator flupirtine hyperpolarized Hcrt neurons and rejuvenated sleep architecture in aged mice.	flupirtine	163-173	hypocretin	Mus musculus	189-193
32796515-4	2020	Flupirtine and its new allyl carbamate derivative (compound 6) confer neuroprotective effects in CLN3-deficient cells.	flupirtine	0-10	CLN3 lysosomal/endosomal transmembrane protein, battenin	Homo sapiens	97-101
32796515-14	2020	In conclusion, flupirtine improved behavioral, neuropathological and biochemical parameters in Cln3Deltaex7/8 mice, paving the way for potential therapies for CLN3 disease.	flupirtine	15-25	ceroid lipofuscinosis, neuronal 3, juvenile (Batten, Spielmeyer-Vogt disease)	Mus musculus	159-163
34132108-0	2021	Flupirtine enhances NHE-3 mediated Na+ absorption in rat colon via an ENS-dependent mechanism.	flupirtine	0-10	solute carrier family 9 member A3	Rattus norvegicus	20-25
34132108-7	2021	The NHE-3-selective inhibitor, S3226, significantly inhibited flupirtine-stimulated Na+ absorption whereas the NHE-2-selective inhibitor HOE-694 did not.	flupirtine	62-72	solute carrier family 9 member A3	Rattus norvegicus	4-9
34132108-8	2021	NHE-3 localization near the apical membranes of surface epithelial cells was also more apparent in flupirtine-treated colon versus control.	flupirtine	99-109	solute carrier family 9 member A3	Rattus norvegicus	0-5
34132108-11	2021	Together, these data indicate that flupirtine stimulates NHE-3-dependent Na+ absorption, likely as a result of reduced stimulatory input to the colonic epithelium by submucosal ENS neurons.	flupirtine	35-45	solute carrier family 9 member A3	Rattus norvegicus	57-62
33791156-7	2021	Through an initiate pilot screening with around 100 compounds, Flupirtine, a selective neuronal potassium channel opener, was identified as a potential TMPRSS2 inhibitor from an FDA-approved drug library by using this screening platform, and showed inhibitory effect on the TMPRSS-dependent infection of SARS-CoV-2 Spike-pseudotyped lentiviral particles.	flupirtine	63-73	transmembrane serine protease 2	Homo sapiens	152-159
33791156-7	2021	Through an initiate pilot screening with around 100 compounds, Flupirtine, a selective neuronal potassium channel opener, was identified as a potential TMPRSS2 inhibitor from an FDA-approved drug library by using this screening platform, and showed inhibitory effect on the TMPRSS-dependent infection of SARS-CoV-2 Spike-pseudotyped lentiviral particles.	flupirtine	63-73	surface glycoprotein	Severe acute respiratory syndrome coronavirus 2	315-320
33791156-8	2021	This study describes a platform proven effective for rapidly screening of TMPRSS2 inhibitors, and suggests that Flupirtine may be worthy of further consideration of repurposing to treat COVID-19 patients.	flupirtine	112-122	transmembrane serine protease 2	Homo sapiens	74-81
30028988-0	2018	In vitro approach to elucidate the relevance of carboxylesterase 2 and N-acetyltransferase 2 to flupirtine-induced liver injury.	flupirtine	96-106	carboxylesterase 2	Homo sapiens	48-66
30652063-0	2019	Flupirtine Analogues: Explorative Synthesis and Influence of Chemical Structure on KV7.2/KV7.3 Channel Opening Activity.	flupirtine	0-10	potassium voltage-gated channel subfamily Q member 2	Homo sapiens	83-88
30652063-0	2019	Flupirtine Analogues: Explorative Synthesis and Influence of Chemical Structure on KV7.2/KV7.3 Channel Opening Activity.	flupirtine	0-10	potassium voltage-gated channel subfamily Q member 3	Homo sapiens	89-94
30652063-1	2019	Neuronal voltage-gated potassium channels KV7.2/KV7.3 are sensitive to small-molecule drugs such as flupirtine, even though physiological response occurs in the absence of ligands.	flupirtine	100-110	potassium voltage-gated channel subfamily Q member 2	Homo sapiens	42-47
30652063-1	2019	Neuronal voltage-gated potassium channels KV7.2/KV7.3 are sensitive to small-molecule drugs such as flupirtine, even though physiological response occurs in the absence of ligands.	flupirtine	100-110	potassium voltage-gated channel subfamily Q member 3	Homo sapiens	48-53
30028988-0	2018	In vitro approach to elucidate the relevance of carboxylesterase 2 and N-acetyltransferase 2 to flupirtine-induced liver injury.	flupirtine	96-106	N-acetyltransferase 2	Homo sapiens	71-92
30028988-5	2018	Using recombinant enzymes, we found that D-13223 was formed from flupirtine via hydrolysis by carboxylesterase 2 (CES2) and subsequent acetylation by N-acetyltransferase (NAT) 2.	flupirtine	65-75	carboxylesterase 2	Homo sapiens	94-112
30028988-5	2018	Using recombinant enzymes, we found that D-13223 was formed from flupirtine via hydrolysis by carboxylesterase 2 (CES2) and subsequent acetylation by N-acetyltransferase (NAT) 2.	flupirtine	65-75	carboxylesterase 2	Homo sapiens	114-118
30028988-5	2018	Using recombinant enzymes, we found that D-13223 was formed from flupirtine via hydrolysis by carboxylesterase 2 (CES2) and subsequent acetylation by N-acetyltransferase (NAT) 2.	flupirtine	65-75	N-acetyltransferase 2	Homo sapiens	150-177
30028988-6	2018	A conjugate of N-acetyl-l-cysteine (NAC), a nucleophile, was detected by incubation of flupirtine with CES2, and the conjugate formation in human liver microsomes was inhibited by CES2 inhibitors, indicating that a reactive metabolite, which may be a quinone diimine, was produced in the process of CES2-mediated hydrolysis of flupirtine.	flupirtine	87-97	X-linked Kx blood group	Homo sapiens	36-39
30028988-6	2018	A conjugate of N-acetyl-l-cysteine (NAC), a nucleophile, was detected by incubation of flupirtine with CES2, and the conjugate formation in human liver microsomes was inhibited by CES2 inhibitors, indicating that a reactive metabolite, which may be a quinone diimine, was produced in the process of CES2-mediated hydrolysis of flupirtine.	flupirtine	87-97	carboxylesterase 2	Homo sapiens	103-107
30028988-6	2018	A conjugate of N-acetyl-l-cysteine (NAC), a nucleophile, was detected by incubation of flupirtine with CES2, and the conjugate formation in human liver microsomes was inhibited by CES2 inhibitors, indicating that a reactive metabolite, which may be a quinone diimine, was produced in the process of CES2-mediated hydrolysis of flupirtine.	flupirtine	327-337	X-linked Kx blood group	Homo sapiens	36-39
30028988-7	2018	The formation of the NAC conjugate in liver S9 samples from NAT2 slow acetylators was significantly higher than that from NAT2 rapid/intermediate acetylators, indicating that NAT2 could function as a detoxification enzyme for flupirtine.	flupirtine	226-236	X-linked Kx blood group	Homo sapiens	21-24
30028988-7	2018	The formation of the NAC conjugate in liver S9 samples from NAT2 slow acetylators was significantly higher than that from NAT2 rapid/intermediate acetylators, indicating that NAT2 could function as a detoxification enzyme for flupirtine.	flupirtine	226-236	N-acetyltransferase 2	Homo sapiens	60-64
30028988-8	2018	CES2-overexpressing HepG2 cells showed remarkable lactate dehydrogenase leakage under flupirtine treatment, while no cytotoxicity was observed in control cells, suggesting that the reactive metabolite formed by CES2-mediated hydrolysis of flupirtine would be a trigger of hepatotoxicity.	flupirtine	86-96	carboxylesterase 2	Homo sapiens	0-4
30028988-8	2018	CES2-overexpressing HepG2 cells showed remarkable lactate dehydrogenase leakage under flupirtine treatment, while no cytotoxicity was observed in control cells, suggesting that the reactive metabolite formed by CES2-mediated hydrolysis of flupirtine would be a trigger of hepatotoxicity.	flupirtine	86-96	carboxylesterase 2	Homo sapiens	211-215
30028988-8	2018	CES2-overexpressing HepG2 cells showed remarkable lactate dehydrogenase leakage under flupirtine treatment, while no cytotoxicity was observed in control cells, suggesting that the reactive metabolite formed by CES2-mediated hydrolysis of flupirtine would be a trigger of hepatotoxicity.	flupirtine	239-249	carboxylesterase 2	Homo sapiens	0-4
30028988-8	2018	CES2-overexpressing HepG2 cells showed remarkable lactate dehydrogenase leakage under flupirtine treatment, while no cytotoxicity was observed in control cells, suggesting that the reactive metabolite formed by CES2-mediated hydrolysis of flupirtine would be a trigger of hepatotoxicity.	flupirtine	239-249	carboxylesterase 2	Homo sapiens	211-215
30028988-9	2018	NAT2 slow acetylators with high CES2 activity could be highly susceptible to flupirtine-induced liver injury.	flupirtine	77-87	N-acetyltransferase 2	Homo sapiens	0-4
30028988-9	2018	NAT2 slow acetylators with high CES2 activity could be highly susceptible to flupirtine-induced liver injury.	flupirtine	77-87	carboxylesterase 2	Homo sapiens	32-36
26959717-0	2016	HLA-DRB1*16: 01-DQB1*05: 02 is a novel genetic risk factor for flupirtine-induced liver injury.	flupirtine	63-73	major histocompatibility complex, class II, DR beta 1	Homo sapiens	0-8
28125509-0	2017	KCNQ2/3 channel agonist flupirtine reduces cocaine place preference in rats.	flupirtine	24-34	potassium voltage-gated channel subfamily Q member 2	Rattus norvegicus	0-7
28125509-2	2017	We tested the hypothesis that flupirtine (FLU) (2.5, 10, 20 mg/kg), a KCNQ2/3 agonist, reduces cocaine (15 mg/kg) conditioned place preference.	flupirtine	30-40	potassium voltage-gated channel subfamily Q member 2	Rattus norvegicus	70-75
28125509-2	2017	We tested the hypothesis that flupirtine (FLU) (2.5, 10, 20 mg/kg), a KCNQ2/3 agonist, reduces cocaine (15 mg/kg) conditioned place preference.	flupirtine	42-45	potassium voltage-gated channel subfamily Q member 2	Rattus norvegicus	70-75
28125509-5	2017	The disruption of cocaine place preference by FLU suggests that KCNQ2/3 channels influence cocaine"s rewarding effects.	flupirtine	46-49	potassium voltage-gated channel subfamily Q member 2	Rattus norvegicus	64-69
26959717-0	2016	HLA-DRB1*16: 01-DQB1*05: 02 is a novel genetic risk factor for flupirtine-induced liver injury.	flupirtine	63-73	major histocompatibility complex, class II, DQ beta 1	Homo sapiens	16-20
26959717-8	2016	RESULTS: In the six flupirtine DILI cases included in the GWAS, we found a significant enrichment of the DRB1*16:01-DQB1*05:02 haplotype compared with the controls (minor allele frequency cases 0.25 and minor allele frequency controls 0.013; P=1.4 x 10(-5)).	flupirtine	20-30	major histocompatibility complex, class II, DR beta 1	Homo sapiens	105-109
26959717-8	2016	RESULTS: In the six flupirtine DILI cases included in the GWAS, we found a significant enrichment of the DRB1*16:01-DQB1*05:02 haplotype compared with the controls (minor allele frequency cases 0.25 and minor allele frequency controls 0.013; P=1.4 x 10(-5)).	flupirtine	20-30	major histocompatibility complex, class II, DQ beta 1	Homo sapiens	116-120
26999128-8	2016	However, activation of KV7.3 by flupirtine did not produce notable changes in matrix mineralization during osteoblast differentiation.	flupirtine	32-42	potassium voltage-gated channel subfamily Q member 3	Homo sapiens	23-28