ライフサイエンスコーパス: antifolate

1 istance to TS-directed fluoropyrimidines and antifolates ().

2 served with cisplatin in combination with an antifolate.

3 n with neoplastic diseases treated with this antifolate.

4 blasts when incubated with this radiolabeled antifolate.

5 nic acid analogues of folic acid and related antifolates.

6 emonstrates activity superior to traditional antifolates.

7 acilitates membrane transport of folates and antifolates.

8 forms is also potentiated for MTX and other antifolates.

9 rnalized more rapidly than other traditional antifolates.

10 ein levels by methotrexate and certain other antifolates.

11 6 nm, respectively, compared with most other antifolates.

12 ional binding pocket that is not occupied by antifolates.

13 Therapy included glucocorticoids and antifolates.

14 ued by further design of sulfonyl-containing antifolates.

15 rtially restricted, linear tricyclic 5-deaza antifolates.

16 folate homeostasis and antitumor response to antifolates.

17 on of dUTP pools and enhanced sensitivity to antifolates.

18 apeutic potency and selectivity of classical antifolates.

19 otection by folic acid of cells to the other antifolates.

20 se may be important in the efficacy of these antifolates.

21 ipates in the internalization of folates and antifolates.

22 ot invariably render cells more sensitive to antifolates.

23 ubstituted pyrrolo[2,3-d]pyrimidine thienoyl antifolates.

24 ate metabolism and therapeutic outcomes with antifolates.

25 mission intensity and frequent resistance to antifolates.

26 roperties, augments transport of folates and antifolates.

27 tively targeting tumors with novel cytotoxic antifolates.

28 for leucovorin), that is hypersusceptible to antifolates.

29 mutants lacking MTHFS became susceptible to antifolates.

30 o sensitize bacterial pathogens to classical antifolates.

31 lications regarding the action of pABA-based antifolates.

32 hese compounds distinct from all other known antifolates.

33 In a complex with dUMP and the antifolate 10-propargyl-5,8-dideazafolate (CB3717), dUMP

34 al antifolates (3 and 4) and 17 nonclassical antifolates (11-27) were synthesized as antitumor and/or

35 Two series of nonclassical antifolates (2,4-diamino-5-deaza compounds 2-5 and 5,10-

36 of the ternary complex of NADPH, the potent antifolate [2, 4-diamino-5- inverted question mark3-[3-(

37 Nonclassical antifolates, 2,4-diamino-5-substituted-furo[2, 3-d]pyrim

38 Novel classical antifolates (3 and 4) and 17 nonclassical antifolates (1

39 The classical antifolate 7 utilized 4-(chloromethyl)benzoyl-l-glutamic

40 es of 2-9 nM, making the parent form of this antifolate a tight-binding inhibitor.

41 tion studies of classical two-carbon bridged antifolates, a 5-substituted 2,4-diaminofuro[2,3-d]pyrim

42 iously reported classical two-carbon-bridged antifolates, a 5-substituted 2,4-diaminofuro[2,3-d]pyrim

43 ng the relationship between GGH activity and antifolate action and may potentially be used in clinica

44 lays a central role in folate metabolism and antifolate action.

45 Antifolate activity was determined by urinary levels of

46 ar needs for folates and as a determinant of antifolate activity, respectively.

47 dge were synthesized and tested for in vitro antifolate activity.

48 confers substantial resistance of animals to antifolate administration.

49 ansduced tumor was detected in animals after antifolate administration.

50 and 5'-fluoro-2'-deoxyuridine (FdUrd) or the antifolates AG337, ZD1694, and BW1843U89, are widely use

51 Methotrexate (MTX) is an antifolate agent that is often associated with toxicity.

52 We found that upon binding of the antifolate agents raltitrexed and nolatrexed, the two in

53 ibuting mechanism of cytotoxicity induced by antifolate agents.

54 and the specificity of the two isoforms for antifolates also differed, suggesting different architec

55 city of thymidine deprivation induced by the antifolate aminopterin was measured in a series of mutan

56 Both proteins also mediate transport of the antifolate analogs methotrexate and aminopterin, as evid

57 yrimidine, afforded the three-carbon-bridged antifolates analogues 4 and 5, with enhanced inhibitory

58 midine (2), afforded two four-carbon bridged antifolates, analogues 5 and 6, with enhanced FPGS subst

59 However, antifolate and pyrethroid resistance threaten the effect

60 Resistance markers for antifolates and chloroquine were also highly prevalent.

61 Consequently, antifolates and FA-linked chemotherapeutic agents that c

62 Because many antifolates and folic acid-linked chemotherapeutic agent

63 toxicity associated with the combined use of antifolates and NBMPR-P and thereby may provide a strate

64 marrow cells against combined treatment with antifolates and nitrobenzylmercaptopurine riboside (NBMP

65 ith natural product chemotherapeutic agents, antifolates and nucleotide analogs, but also into factor

66 tivity of the active thieno[2,3-d]pyrimidine antifolates and the FR specificity represent unique mech

67 ponsible for intrinsic resistance to various antifolates and this pathway is a chemically vulnerable

68 containing nanomolar concentrations of this antifolate, and vacuolar membrane-enriched vesicles puri

69 ydrofolate reductase (DHFR) is the target of antifolate antimalarial drugs such as pyrimethamine and

70 Antifolate antimalarials, such as pyrimethamine, have ex

71 atens to curtail the therapeutic lifetime of antifolate antimalarials.

72 olate/antifolate intracellular retention and antifolate antitumor activity, displays a pronounced spe

73 n against CCRF-CEM cells when both AICAr and antifolate are present for the first 24 hours of a 120-h

74 The antifolates are an important and affordable antimalarial

75 Antifolates are an underutilized drug class in tuberculo

76 ough chloroquine remains the drug of choice, antifolates are effective against P vivax malaria in Sou

77 Cells that are resistant to antifolates are generally less resistant to pemetrexed,

78 les that confer high levels of resistance to antifolates are rare, even in eastern and southern Afric

79 onjugates but also folate monoglutamates and antifolates as exemplified by pteroyl-l-glutamic acid an

80 Thymidylate synthase (TS) is a target for antifolate-based chemotherapies of microbial and human d

81 d bone marrow cells and then treated with an antifolate-based regimen that kills unmodified stem cell

82 tment of HCT-8 cells with ZD1694, a specific antifolate-based thymidylate synthase inhibitor, resulte

83 In contrast to conventional antifolates, BGC 945 has low affinity for the widely exp

84 n suggested to be important for cofactor and antifolate binding.

85 rexate transport were inhibited by classical antifolates but not by non-classical antifolates or biop

86 endent efflux system for certain folates and antifolates, but that its transport characteristics with

87 ssible to increase the antitumor activity of antifolates by the coadministration of drugs that inhibi

88 Pemetrexed represents the first antifolate cancer drug to be approved by the Food and Dr

89 e synthesized via straightforward methods of antifolate chemistry, and their properties were compared

90 nt in DHPS also abolished the synergy of the antifolate combination pyrimethamine/sulfadoxine.

91 The antifolate combination pyrimethamine/sulphadoxine (PYR/S

92 erring mid- and high-level resistance to the antifolate combination sulfadoxine-pyrimethamine have a

93 oing effort to discover novel small-molecule antifolates combining the enzyme-binding species selecti

94 ubstituted pyrrolo[2,3-d]pyrimidine thienoyl antifolate (compound 1) was used to establish whether PC

95 tures of four pyrrolo(2,3-d)pyrimidine-based antifolate compounds, developed as inhibitors of thymidy

96 sized 5-substituted pyrrolo[2,3-d]pyrimidine antifolates (compounds 5-10) with one-to-six bridge carb

97 This effect depended on the antifolate concentration and was independent of the fusi

98 regimens and other modalities incorporating antifolates, conjugates, histone deacetylase inhibitors,

99 -ornithine (1, PT523), a nonpolyglutamatable antifolate currently in advanced preclinical development

100 4) is a novel pyrrolo[2,3-d]pyrimidine-based antifolate currently undergoing extensive Phase II clini

101 Antifolates currently in the clinic, such as pemetrexed,

102 e compounds and thereby indirectly influence antifolate cytotoxicity, and it also implies that this p

103 ave been demonstrated to prevent rescue from antifolate cytotoxicity, mediated by nucleoside salvage.

104 Pralatrexate is an antifolate designed to be internalized more rapidly than

105 Pralatrexate is a novel antifolate designed to have high affinity for the reduce

106 highly selective, novel target for potential antifolate development in malaria.

107 polyglutamylatable and nonpolyglutamylatable antifolates, directed against dihydrofolate reductase (D

108 Resistance to this antifolate directly correlated with BCRP expression, and

109 R), 15-fold lower than that of the classical antifolate drug methotrexate (MTX).

110 mine, the antimalarial drug amodiaquine, the antifolate drug metoprine, and the anticholinesterase dr

111 th potentiation of ADI-PEG20 activity by the antifolate drug pemetrexed.

112 It is a novel antifolate drug resembling TS inhibitors plevitrexed and

113 PTR1 contributes to antifolate drug resistance by providing a molecular bypa

114 c progenitors expressing increased levels of antifolate drug resistance could be enriched from the GF

115 e reductase (PTR1) is a major contributor to antifolate drug resistance in Leishmania spp., as it pro

116 d TbFT1-3 loss-of-function is a mechanism of antifolate drug resistance.

117 nd formally prove the role of this enzyme in antifolate drug synergy and folate biosynthesis in vivo.

118 er family, TbFT1-3, as major contributors to antifolate drug uptake.

119 ystathionine beta-synthase gene and/or by an antifolate drug, aminopterin (which prevents remethylati

120 D1L knockdown or the use of methotrexate, an antifolate drug, sensitizes cancer cells to sorafenib, a

121 o test the relative efficacy and safety of 2 antifolate drugs against P vivax malaria and compare eac

122 eir human counterparts, existing active-site antifolate drugs can have dose-limiting toxicities.

123 Resistance to chloroquine and antifolate drugs has evolved independently in South Amer

124 and characterize mechanisms of resistance to antifolate drugs in African trypanosomes.

125 ared to be more efficient than sulfonamides, antifolate drugs known to inhibit the invasion and proli

126 f adverse effects associated with taking two antifolate drugs simultaneously.

127 Antifolate drugs such as methotrexate are commonly used

128 as may render these tumors more sensitive to antifolate drugs such as methotrexate.

129 igh folate status may reduce the response to antifolate drugs used against malaria, rheumatoid arthri

130 c possibilities to selectively deliver novel antifolate drugs via transport by PCFT over RFC by explo

131 f the genes coding for the target enzymes of antifolate drugs, dihydrofolate reductase (DHFR) and dih

132 ate derivatives of folate cofactors and many antifolate drugs.

133 onfers resistance to bacterial DHFR-targeted antifolate drugs.

134 cusses how to extend the therapeutic life of antifolate drugs.

135 atopoietic cells resist the toxic effects of antifolate drugs.

136 quired before reduced folates and anticancer antifolates [e.g., methotrexate (MTX)] exert their physi

137 Pemetrexed is a novel antifolate effective in the treatment of mesothelioma.

138 ith a higher affinity for PMX than the other antifolates evaluated.

139 Antifolates, folate analogs that inhibit vitamin B9 (fol

140 on of anti-FRalpha antibodies, high-affinity antifolates, folate-based imaging agents and folate-conj

141 long-chain gamma-glutamyl derivatives of the antifolate for HT-1080 and another human sarcoma line.

142 ductase and therefore compromises the use of antifolates for treatment of trypanosomiasis.

143 Clinical resistance to antifolates has been mainly attributed to mutations that

144 Antifolates have a proven record as clinically used onco

145 rtaken to characterize the transport of this antifolate in this tumor.

146 Cellular uptake of the antifolates in clinical use occurs primarily via widely

147 f three other pyrrolo(2,3-d)pyrimidine-based antifolates in complex with Escherichia coli TS confirm

148 ity of pemetrexed, but not that of the other antifolates in HepG2 cells grown with 5-formyltetrahydro

149 e major membrane transporter for folates and antifolates in mammalian tissues.

150 yme conferred resistance to FdUrd as well as antifolates in transfected cells.

151 mediates the uptake of folate and classical antifolates in trypanosomes, and TbFT1-3 loss-of-functio

152 ubstituted pyrrolo[2,3-d]pyrimidine thienoyl antifolates in which the terminal l-glutamate of the par

153 l evidence demonstrating that lethality from antifolates in yeast is primarily dependent on uracil mi

154 the activity of pemetrexed, a multitargeted antifolate, in squamous cell carcinoma of the head and n

155 Several antifolates, including trimethoprim (TMP) and a series o

156 The affinities of the antifolates increase up to 60-fold with the Y102F mutant

157 eral mechanisms by which PTR1 may compromise antifolate inhibition in wild-type Leishmania and lines

158 ms while raltitrexed (Tomudex, ZD1694) is an antifolate inhibitor of TS approved for clinical use in

159 ductase (DHFR) and compound 7 as a classical antifolate inhibitor of tumor cells in culture.

160 h with bound NADPH cofactor and a lipophilic antifolate inhibitor, have been determined at atomic res

161 n, PDPA shows positive cooperativity with an antifolate inhibitor, ZD9331, which binds to the active

162 pyrimidines 1-6 are reported as nonclassical antifolate inhibitors of dihydrofolate reductase (DHFR)

163 n apparent relatively low affinity for other antifolate inhibitors of dihydrofolate-reductase (MTX, a

164 ross-resistance patterns with new-generation antifolate inhibitors of tetrahydrofolate cofactor-depen

165 revealed a unique binding mode compared with antifolate inhibitors.

166 (fpgs) gene, whose product determines folate/antifolate intracellular retention and antifolate antitu

167 erexpressors were differentially affected by antifolates known to inhibit parasite growth via targets

168 Tests with two antifolates led to the recovery of cosmids encoding DHFR

169 The maintenance of antifolate levels in animals protected from MTX toxicity

170 C8-N9 bridged analogues of the multitargeted antifolate LY231514 were synthesized as inhibitors of th

171 th one of the inhibitors, the multi-targeted antifolate LY231514, demonstrates that this compound ind

172 for the relatively selective action certain antifolates may have against MTAP-deficient malignancies

173 Cellular resistance to the antifolate methotrexate (MTX) is often caused by target

174 e, MCF7/MX, is highly cross-resistant to the antifolate methotrexate (MTX), because of enhanced ATP-d

175 R protein increase following exposure to the antifolate methotrexate (MTX), suggesting that MTX may r

176 ve polyglutamates of natural folates and the antifolate methotrexate (MTX).

177 3 when the folate cycle was inhibited by the antifolate methotrexate and to 12-14 when BHMT expressio

178 nown and may affect the effectiveness of the antifolate methotrexate for the treatment of psoriasis.

179 nant TbPTR1 and inhibition by the archetypal antifolate methotrexate have been characterized and the

180 The antifolate methotrexate is one of the most successful dr

181 the parasite's susceptibly to the classical antifolates methotrexate and raltitrexed.

182 tream form Trypanosoma brucei exposed to the antifolates methotrexate and raltitrexed.

183 Multitargeted antifolate (MTA) is an investigational agent that, like

184 oma cells was decreased by the multitargeted antifolate (MTA), LY231514.

185 We designed and synthesized a classical antifolate N-{4-[(2-amino-6-methyl-4-oxo-3,4-dihydro-5 H

186 Two novel classical antifolates N-{4-[(2,4-diamino-5-methyl-4,7-dihydro-3H-p

187 B-ring analogues of the nonpolyglutamatable antifolate Nalpha-(4-amino-4-deoxypteroyl)-Ndelta-hemiph

188 Compounds 2-5 were designed as potential antifolate nonpolyglutamatable inhibitors of thymidylate

189 ubstituted pyrrolo[2,3-d]pyrimidine thienoyl antifolates offer significant promise for treating NS-NS

190 vities of four-carbon-atom bridged classical antifolates on dihydrofolate reductase (DHFR), thymidyla

191 assical antifolates but not by non-classical antifolates or biopterin.

192 for the specific delivery of new classes of antifolates or folate conjugates to tumors or sites of i

193 n established anti-infective target, and the antifolate para-aminosalicylic acid (PAS) was one of the

194 r from inhibition of purine synthesis by the antifolate pemetrexed (PTX), a drug used extensively in

195 R in complex with three clinically prevalent antifolates, pemetrexed (also Alimta), aminopterin, and

196 specific and convergent route the lipophilic antifolate piritrexim (PTX) is described in which a key

197 part of a program to design propargyl-linked antifolates (PLAs) against trimethoprim-resistant dihydr

198 e have developed a class of propargyl-linked antifolates (PLAs) that exhibit potent inhibition of the

199 h polyglutamylation, augmented hydrolysis of antifolate polyglutamates, increased expression and muta

200 During the consolidation phase, when antifolates predominated, the reduced folate carrier pol

201 3 increased susceptibly to the non-classical antifolates pyrimethamine and nolatrexed.

202 f point mutations in enzymes targeted by the antifolates, pyrimethamine and sulphadoxine.

203 ubstituted pyrrolo[2,3-d]pyrimidine thienoyl antifolates related to PMX [compound 1 (C1) and compound

204 exed and to the activities of this and other antifolates relative to RFC at physiological pH.

205 epresents a low-affinity transport route for antifolates (relative affinities: raltitrexed > pemetrex

206 by MTHFS is required for bacterial intrinsic antifolate resistance and folate homeostatic control.

207 roteins from bacteria or human restored both antifolate resistance and folinic acid utilization to FU

208 ctor in mechanisms of acquired and intrinsic antifolate resistance has been reported for several cult

209 reconstruction of the probable phylogeny of antifolate resistance in malaria.

210 This novel mechanism of antimicrobial antifolate resistance might be targeted to sensitize bac

211 Antifolate resistance mutations were common, with appare

212 scribes the bases for intrinsic and acquired antifolate resistance within the context of the current

213 To better define the role of PCFT in antifolate resistance, a methotrexate-resistant cell lin

214 ssion is yet another mechanism for acquiring antifolate resistance, overexpression of FR does not inv

215 Considering antifolate resistance, SP was associated with increased

216 asmodium falciparum that are associated with antifolate resistance.

217 ed and evaluated for their ability to impart antifolate resistance.

218 l PABA biosynthesis contributes to intrinsic antifolate resistance.

219 in essential pteridine salvage as well as in antifolate resistance.

220 valence, malaria transmission intensity, and antifolate resistance.

221 tion of the altered enzymes and formation of antifolate-resistant colonies in mouse bone marrow cells

222 tructed two retroviral vectors containing an antifolate-resistant dihydrofolate reductase cDNA transc

223 ined in vitro potency against newly emerging antifolate-resistant malaria parasites.

224 tified 5-fluoro-2'-deoxyuridine (5-FdUR) and antifolate-resistant mutants of human thymidylate syntha

225 to use molecular markers for surveillance of antifolate-resistant P. falciparum malaria in Africa.

226 nity of this transporter for BSP relative to antifolates seems to be intrinsic to its binding site an

227 h folic acid as the sole folate source under antifolate selective pressure.

228 nd this is associated with impaired vacuolar antifolate sequestration.

229 Human cells exposed to antifolates show a rapid increase in the levels of the e

230 larly LmQDPR is not inhibited by a series of antifolates showing anti-leishmanial activity beyond tha

231 mple of a classical pyrrolo[2,3-d]pyrimidine antifolate shown to have this alternate mode of binding

232 es this phenomenon, suggesting the design of antifolates specific for activation by individual FPGS i

233 ufficient to mediate transport of folate and antifolate substrates.

234 While antifolates such as Bactrim (trimethoprim-sulfamethoxazo

235 Antifolates such as methotrexate (MTX) and trimetrexate

236 glutamate derivatives of reduced folates and antifolates such as methotrexate and 5,10-dideaza-5,6,7,

237 h as 5-methyl tetrahydrofolate and classical antifolates such as methotrexate are actively transporte

238 to the purine de novo inhibitory actions of antifolates such as methotrexate than are p16+, MTAP+ ce

239 bolism of folic acid and the pharmacology of antifolates such as methotrexate.

240 bolism of folic acid and the pharmacology of antifolates such as methotrexate.

241 esidues from the polyglutamyl of folates and antifolates, such as methotrexate (MTX), a widely used a

242 Although classic antifolates, such as methotrexate, have been developed a

243 colony-forming units-spleen are resistant to antifolates, suggesting that myelotoxicity occurs late i

244 We conclude that the primary basis for antifolate synergy in these organisms arises from PYR ta

245 Tomudex is one of several new antifolates targeted to TS and the first to be approved

246 r knowledge, this is the first example of an antifolate that acts as a dual inhibitor of GARFTase and

247 to our knowledge, of a 2,4-diamino classical antifolate that has potent inhibitory activity against b

248 Pemetrexed is a novel antifolate that inhibits multiple enzymes necessary for

249 n treated with PALA or with methotrexate, an antifolate that, under the conditions used, should not g

250 le to develop clinically useful nonclassical antifolates that are both potent and selective against t

251 this study demonstrates that, for classical antifolates that are substrates for FPGS, poor inhibitor

252 be ideal, previous attempts have resulted in antifolates that exhibit inconsistencies between enzyme

253 oic acid (PABA) can antagonize the action of antifolates that interact with dihydropteroate synthase

254 the evaluation of pairs of propargyl-linked antifolates that possess similar physicochemical propert

255 ntially be used in clinical combination with antifolates that require polyglutamylation for effective

256 lls are placed under selective pressure with antifolates that utilize RFC1 as the major route of entr

257 a suggest that LY231514 is a novel classical antifolate, the antitumor activity of which may result f

258 For half a century, successful antifolate therapy against Plasmodium falciparum malaria

259 orms and hence tissue-selective targeting of antifolate therapy for cancer, arthritis, or psoriasis.

260 variations in FPGS may alter the efficacy of antifolate therapy in cancer patients.

261 4-oxo-6-substituted-pyrrolo[2,3-d]pyrimidine antifolate thiophene regioisomers of AGF94 (4) with a th

262 ugmented drug export, impaired activation of antifolates through polyglutamylation, augmented hydroly

263 iew that polyglutamation enhances binding of antifolates to GARFT.

264 veral diseases, and the possibility of using antifolates to inhibit enzymes from Mycobacterium tuberc

265 FRs and distinct binding modes of folate and antifolates to these receptors.

266 tumors that can selectively target cytotoxic antifolates to tumors under acidic microenvironment cond

267 er shown to be associated with quinoline and antifolate tolerance in Plasmodium falciparum.

268 scribes highly pH-dependent OATP2B1-mediated antifolate transport and compares this property with tha

269 The folate/antifolate transporter with the widest tissue distributi

270 The level of fusion protein in antifolate-treated human tumor cells was increased in re

271 Thus, antifolate treatment does not relieve translational inhi

272 ution, reveals that TAB binds similar to the antifolates trimethoprim and methotrexate.

273 own to be insensitive to the clinically used antifolate, trimethoprim, because of a lack of potency a

274 sion protein and subsequently exposed to the antifolate trimetrexate (TMTX) showed a specific and tim

275 ng good catalytic function and resistance to antifolate TS inhibitors, confirm the importance of amin

276 es from areas with a history of longstanding antifolate use.

277 is a 5-substituted pyrrolo[2,3-d]pyrimidine antifolate used for therapy of nonsquamous nonsmall cell

278 rgue that arginine deprivation combined with antifolates warrants clinical investigation in ASS1-nega

279 ning, ortho-icosahedral carborane lipophilic antifolates were synthesized, and the crystal structures

280 The antifolates were the first class of antimetabolites to e

281 e ecTS is intrinsically resistant to several antifolates when compared with human TS, we suspected th

282 ors against the toxic effects of 3 different antifolates when each was combined with NBMPR.

283 Pemetrexed disodium is a potent new antifolate which inhibits many folate-dependent reaction

284 Pralatrexate is a novel antifolate, which shows increased antitumor activity in

285 Antifolates, which are among the first antimicrobial age

286 he growth-inhibitory actions of agents (e.g. antifolates) whose mechanism of action in part involves

287 Pralatrexate is a novel antifolate with high affinity for reduced folate carrier

288 Pemetrexed is a multitargeted antifolate with manageable toxicity and has been combine

289 selective, nonclassical, orally bioavailable antifolate with potent and specific inhibitory activity

290 cy and tolerability of pralatrexate, a novel antifolate with promising activity.

291 formed in cells from AMT and other classical antifolates with a glutamate side chain.

292 bstituted classical pyrrolo[2,3-d]pyrimidine antifolates with a three- to six-carbon bridge between t

293 ubstituted pyrrolo[2,3-d]pyrimidine thienoyl antifolates with four or three bridge carbons [compound

294 ested 6-substituted pyrrolo[2,3-d]pyrimidine antifolates with one to six carbons in the bridge region

295 Thus, solid tumor-targeted antifolates with PCFT-selective cellular uptake should h

296 s of bacterial TSase may assist in designing antifolates with polyglutamyl substitutes as species-spe

297 ed as a promising lead in the search for new antifolates with potential clinical activity against P.

298 Nine classic diamino furo[2,3-d]pyrimidine antifolates with unsubstituted alpha- and gamma-carboxyl

299 The development of specific, FR-targeted antifolates would be accelerated if additional biophysic

300 The experimental antifolate WR99210 inhibited the allele in this system.