PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 29167151-4 2018 Pemetrexed, a high-affinity substrate for PCFT, decreased or abolished biotinylation of seven of these residues consistent with their location in or near the folate binding pocket. Pemetrexed 0-10 solute carrier family 46 member 1 Homo sapiens 42-46 32493992-1 2020 BACKGROUND: Expression of proton-coupled folate transporter (PCFT) is associated with survival of mesothelioma patients treated with pemetrexed, and is reduced by hypoxia, prompting studies to elucidate their correlation. Pemetrexed 133-143 solute carrier family 46 member 1 Homo sapiens 61-65 34040256-6 2021 Here we present cryo-electron microscopy structures of PCFT in a substrate-free state and in complex with a new-generation antifolate drug (pemetrexed). Pemetrexed 140-150 solute carrier family 46 member 1 Homo sapiens 55-59 31167838-5 2019 The positive controls, methotrexate and pemetrexed, demonstrated clinically relevant inhibition of PCFT, RFC, and FRalpha in folate absorption, distribution, and renal sparing. Pemetrexed 40-50 solute carrier family 46 member 1 Homo sapiens 99-103 29326243-1 2018 The proton-coupled folate transporter (PCFT) is ubiquitously expressed in solid tumors to which it delivers antifolates, particularly pemetrexed, into cancer cells. Pemetrexed 134-144 solute carrier family 46 member 1 Homo sapiens 39-43 23552283-7 2013 Pemetrexed also protected PCFT mutant function from inhibitory modification of the substituted Cys at positions 157, 158, and 161 by a MTS. Pemetrexed 0-10 solute carrier family 46 member 1 Homo sapiens 26-30 29127457-4 2018 For pemetrexed, among the best PCFT substrates, transport by PCFT establishes its importance as a clinically important transporter in malignant pleural mesothelioma and non-small cell lung cancer. Pemetrexed 4-14 solute carrier family 46 member 1 Homo sapiens 31-35 29127457-4 2018 For pemetrexed, among the best PCFT substrates, transport by PCFT establishes its importance as a clinically important transporter in malignant pleural mesothelioma and non-small cell lung cancer. Pemetrexed 4-14 solute carrier family 46 member 1 Homo sapiens 61-65 27251438-9 2016 There was a 6.5-fold decrease in the pemetrexed influx Vmax and a 3.5- and 6-fold decrease in the influx Kt and Ki, respectively, for the W299S PCFT. Pemetrexed 37-47 solute carrier family 46 member 1 Homo sapiens 144-148 24396145-7 2014 Pemetrexed is an excellent substrate for both RFC and PCFT. Pemetrexed 0-10 solute carrier family 46 member 1 Homo sapiens 54-58 24396145-8 2014 Novel tumor-targeted antifolates related to pemetrexed with selective membrane transport by PCFT over RFC are being developed. Pemetrexed 44-54 solute carrier family 46 member 1 Homo sapiens 92-96 28945836-6 2017 Results: Pemetrexed-treated patients with low PCFT had significantly lower rates of disease control, and shorter overall survival (OS), in both the test (N = 73, 11.3 versus 20.1 months, P = 0.01) and validation (N = 51, 12.6 versus 30.3 months, P = 0.02) cohorts. Pemetrexed 9-19 solute carrier family 46 member 1 Homo sapiens 46-50 28945836-10 2017 PCFT silencing reduced pemetrexed sensitivity, whereas 5-aza-2"-deoxycytidine overcame resistance. Pemetrexed 23-33 solute carrier family 46 member 1 Homo sapiens 0-4 26837243-2 2016 PMX is transported by the reduced folate carrier (RFC) and proton-coupled folate transporter (PCFT). Pemetrexed 0-3 solute carrier family 46 member 1 Homo sapiens 94-98 26837243-6 2016 6-Substituted pyrrolo[2,3-d]pyrimidine thienoyl antifolates related to PMX [compound 1 (C1) and compound 2 (C2), respectively] are selective substrates for PCFT over RFC. Pemetrexed 71-74 solute carrier family 46 member 1 Homo sapiens 156-160 24745983-7 2014 Pemetrexed (PMX) is an excellent substrate for PCFT as well as for RFC. Pemetrexed 0-10 solute carrier family 46 member 1 Homo sapiens 47-51 24745983-7 2014 Pemetrexed (PMX) is an excellent substrate for PCFT as well as for RFC. Pemetrexed 12-15 solute carrier family 46 member 1 Homo sapiens 47-51 24745983-8 2014 Novel tumor-targeted antifolates related to PMX with selective membrane transport by PCFT over RFC are being developed. Pemetrexed 44-47 solute carrier family 46 member 1 Homo sapiens 85-89 22345511-6 2012 In contrast, the pemetrexed influx K(t) mediated by P425R-PCFT was decreased 30% compared with wild-type (WT)-PCFT. Pemetrexed 17-27 solute carrier family 46 member 1 Homo sapiens 58-62 22954694-5 2012 The finding that pemetrexed is an excellent PCFT substrate explains its demonstrated clinical efficacy for mesothelioma and non-small cell lung cancer, and prompted development of more PCFT-selective tumor-targeted 6-substituted pyrrolo[2,3-d]pyrimidine antifolates that derive their cytotoxic effects by targeting de novo purine nucleotide biosynthesis. Pemetrexed 17-27 solute carrier family 46 member 1 Homo sapiens 44-48 22954694-5 2012 The finding that pemetrexed is an excellent PCFT substrate explains its demonstrated clinical efficacy for mesothelioma and non-small cell lung cancer, and prompted development of more PCFT-selective tumor-targeted 6-substituted pyrrolo[2,3-d]pyrimidine antifolates that derive their cytotoxic effects by targeting de novo purine nucleotide biosynthesis. Pemetrexed 17-27 solute carrier family 46 member 1 Homo sapiens 185-189 22345511-6 2012 In contrast, the pemetrexed influx K(t) mediated by P425R-PCFT was decreased 30% compared with wild-type (WT)-PCFT. Pemetrexed 17-27 solute carrier family 46 member 1 Homo sapiens 110-114 22345511-7 2012 Methotrexate inhibition of pemetrexed influx was competitive with a K(i) for WT-PCFT comparable to its influx K(t). Pemetrexed 27-37 solute carrier family 46 member 1 Homo sapiens 80-84 22345511-10 2012 Hence, despite its location, the P425R-PCFT mutation produces a conformational change that fully preserves pemetrexed binding but markedly impairs binding of methotrexate and other folates to the carrier. Pemetrexed 107-117 solute carrier family 46 member 1 Homo sapiens 39-43 21940787-4 2011 Both 1 and pemetrexed (Pmx) inhibited proliferation of R1-11-PCFT4 HeLa cells engineered to express PCFT without the reduced folate carrier (RFC) and of HepG2 cells expressing both PCFT and RFC. Pemetrexed 11-21 solute carrier family 46 member 1 Homo sapiens 61-65 21940787-4 2011 Both 1 and pemetrexed (Pmx) inhibited proliferation of R1-11-PCFT4 HeLa cells engineered to express PCFT without the reduced folate carrier (RFC) and of HepG2 cells expressing both PCFT and RFC. Pemetrexed 11-21 solute carrier family 46 member 1 Homo sapiens 100-104 21940787-4 2011 Both 1 and pemetrexed (Pmx) inhibited proliferation of R1-11-PCFT4 HeLa cells engineered to express PCFT without the reduced folate carrier (RFC) and of HepG2 cells expressing both PCFT and RFC. Pemetrexed 23-26 solute carrier family 46 member 1 Homo sapiens 61-65 21940787-4 2011 Both 1 and pemetrexed (Pmx) inhibited proliferation of R1-11-PCFT4 HeLa cells engineered to express PCFT without the reduced folate carrier (RFC) and of HepG2 cells expressing both PCFT and RFC. Pemetrexed 23-26 solute carrier family 46 member 1 Homo sapiens 100-104 20601456-5 2010 Compound 2 and pemetrexed (Pmx) competed with [(3)H]methotrexate for PCFT transport in PCFT-expressing CHO (R2/hPCFT4) cells from pH 5.5 to 7.2; inhibition increased with decreasing pH. Pemetrexed 15-25 solute carrier family 46 member 1 Homo sapiens 69-73 20601456-5 2010 Compound 2 and pemetrexed (Pmx) competed with [(3)H]methotrexate for PCFT transport in PCFT-expressing CHO (R2/hPCFT4) cells from pH 5.5 to 7.2; inhibition increased with decreasing pH. Pemetrexed 15-25 solute carrier family 46 member 1 Homo sapiens 87-91 20601456-5 2010 Compound 2 and pemetrexed (Pmx) competed with [(3)H]methotrexate for PCFT transport in PCFT-expressing CHO (R2/hPCFT4) cells from pH 5.5 to 7.2; inhibition increased with decreasing pH. Pemetrexed 27-30 solute carrier family 46 member 1 Homo sapiens 69-73 20601456-5 2010 Compound 2 and pemetrexed (Pmx) competed with [(3)H]methotrexate for PCFT transport in PCFT-expressing CHO (R2/hPCFT4) cells from pH 5.5 to 7.2; inhibition increased with decreasing pH. Pemetrexed 27-30 solute carrier family 46 member 1 Homo sapiens 87-91 20601456-6 2010 In Xenopus laevis oocytes microinjected with PCFT cRNA, uptake of 2, like that of Pmx, was electrogenic. Pemetrexed 82-85 solute carrier family 46 member 1 Homo sapiens 45-49 17308042-5 2007 This is due to concurrent contraction of competing cellular physiologic folates and utilization of a novel second transport carrier for which pemetrexed has high affinity, recently identified as the proton-coupled folate transporter (PCFT). Pemetrexed 142-152 solute carrier family 46 member 1 Homo sapiens 199-232 17340171-0 2007 The molecular identity and characterization of a Proton-coupled Folate Transporter--PCFT; biological ramifications and impact on the activity of pemetrexed. Pemetrexed 145-155 solute carrier family 46 member 1 Homo sapiens 49-82 17340171-0 2007 The molecular identity and characterization of a Proton-coupled Folate Transporter--PCFT; biological ramifications and impact on the activity of pemetrexed. Pemetrexed 145-155 solute carrier family 46 member 1 Homo sapiens 84-88 17340171-7 2007 This article reviews (1) the characteristics and prevalence of the low-pH folate transport activity, (2) its relationship to, and properties of, the recently identified Proton-Coupled Folate Transporter (PCFT), (3) the physiological and pharmacological roles of this transporter, particularly with respect to pemetrexed, and (4) the historical controversy, now resolved, on the mechanism of intestinal folate absorption. Pemetrexed 309-319 solute carrier family 46 member 1 Homo sapiens 169-202 17340171-7 2007 This article reviews (1) the characteristics and prevalence of the low-pH folate transport activity, (2) its relationship to, and properties of, the recently identified Proton-Coupled Folate Transporter (PCFT), (3) the physiological and pharmacological roles of this transporter, particularly with respect to pemetrexed, and (4) the historical controversy, now resolved, on the mechanism of intestinal folate absorption. Pemetrexed 309-319 solute carrier family 46 member 1 Homo sapiens 204-208 18524888-2 2008 This article addresses the extent to which PCFT contributes to transport of pemetrexed and to the activities of this and other antifolates relative to RFC at physiological pH. Pemetrexed 76-86 solute carrier family 46 member 1 Homo sapiens 43-47 18524888-6 2008 PCFT, expressed at high levels in Xenopus laevis oocytes and in transporter-competent HepG2 cells, exhibited a high affinity for pemetrexed, with an influx K(m) value of 0.2 to 0.8 muM at pH 5.5. Pemetrexed 129-139 solute carrier family 46 member 1 Homo sapiens 0-4 18524888-7 2008 PCFT increased the growth inhibitory activity of pemetrexed, but not that of the other antifolates in HepG2 cells grown with 5-formyltetrahydrofolate at physiological pH. Pemetrexed 49-59 solute carrier family 46 member 1 Homo sapiens 0-4 18524888-8 2008 These findings illustrate the unique role that PCFT plays in the transport and pharmacological activity of pemetrexed. Pemetrexed 107-117 solute carrier family 46 member 1 Homo sapiens 47-51 18524888-9 2008 Because of the ubiquitous expression of PCFT in human tumors, and the ability of PCFT to sustain pemetrexed activity even in the absence of RFC, tumor cells are unlikely to become resistant to pemetrexed as a result of impaired transport because of the redundancy of these genetically distinct routes. Pemetrexed 97-107 solute carrier family 46 member 1 Homo sapiens 81-85 17308042-5 2007 This is due to concurrent contraction of competing cellular physiologic folates and utilization of a novel second transport carrier for which pemetrexed has high affinity, recently identified as the proton-coupled folate transporter (PCFT). Pemetrexed 142-152 solute carrier family 46 member 1 Homo sapiens 234-238