Folic Acid Antagonists
Methotrexate
Tetrahydrofolate Dehydrogenase
An enzyme of the oxidoreductase class that catalyzes the reaction 7,8-dihyrofolate and NADPH to yield 5,6,7,8-tetrahydrofolate and NADPH+, producing reduced folate for amino acid metabolism, purine ring synthesis, and the formation of deoxythymidine monophosphate. Methotrexate and other folic acid antagonists used as chemotherapeutic drugs act by inhibiting this enzyme. (Dorland, 27th ed) EC 1.5.1.3.
Thioguanine
Carcinoma, Ehrlich Tumor
Hypoxanthine Phosphoribosyltransferase
An enzyme that catalyzes the conversion of 5-phosphoribosyl-1-pyrophosphate and hypoxanthine, guanine, or 6-mercaptopurine to the corresponding 5'-mononucleotides and pyrophosphate. The enzyme is important in purine biosynthesis as well as central nervous system functions. Complete lack of enzyme activity is associated with the LESCH-NYHAN SYNDROME, while partial deficiency results in overproduction of uric acid. EC 2.4.2.8.
Phase I study of escalating doses of edatrexate in combination with paclitaxel in patients with metastatic breast cancer. (1/155)
Motivated by the observation of preclinical synergy, a Phase I dose escalation study of edatrexate in combination with a 3-h paclitaxel infusion was performed in patients with advanced breast cancer to determine the maximum tolerated dose (MTD) of edatrexate and the toxicities associated with this combination and to report preliminary observations of efficacy with this novel combination. Thirty-six patients were enrolled in this Phase I trial. Thirty-five eligible patients were treated every 21 days in cohorts of at least three patients and were assessable for toxicity. One patient was ineligible due to hyperbilirubinemia. Stepwise dose escalations of edatrexate were administered until grade >3 nonhematological dose-limiting toxicities were reported. The initial dose level of edatrexate was 180 mg/m2; subsequent cohorts were treated with escalating doses of edatrexate (210, 240, 270, 300, 350, and 400 mg/m2). Edatrexate was administered by i.v. infusion over 1 h. Paclitaxel was administered 24 h later at a fixed dose of 175 mg/m2 as a 3-h infusion with standard dexamethasone, diphenhydramine, and cimetidine premedication. The MTD of edatrexate was reached at the 350 mg/m2 level in this study. Grade 3 diarrhea was seen in one patient at the 300 and 400 mg/m2 dose levels, requiring dose reductions. Two patients experienced grade 4 stomatitis at the 400 mg/m2 dose level and also required dose reduction, establishing the MTD as 350 mg/m2. Grade 3 nausea and vomiting were noted in two of three patients at the highest dose level. Of 35 patients, 4 patients reported grade 3 myalgias and 1 patient reported grade 3 neurosensory complaints, which were seen mostly at the 350 and 400 mg/m2 dose levels; however, 1 patient reported grade 3 myalgias at 180 mg/m2. No cumulative neurotoxicity was observed, and no patient experienced an allergic reaction to paclitaxel. In 23 patients with bidimensionally measurable disease, there were four complete (17%) and seven partial responses, with an overall response rate of 48% (95% confidence interval, 27-69%). All of the responses were seen in patients who had not received prior chemotherapy for stage IV disease. The median duration of response was not assessable because many responding patients went on to receive high-dose chemotherapy treatment with stem cell support. The combination of edatrexate and paclitaxel for treatment of metastatic breast cancer is a feasible and safe regimen. The MTD of edatrexate was 350 mg/m2 when combined with a 3-h infusion of paclitaxel (175 mg/m2) given 24 h later. Activity was noted even among patients who had relapsed shortly after receiving methotrexate- and/or doxorubicin-containing adjuvant regimens. Additional studies evaluating the sequences and dosing schema for this combination are warranted to improve the response proportion and define the duration of the response. (+info)Folylpolyglutamyl synthetase gene transfer and glioma antifolate sensitivity in culture and in vivo. (2/155)
BACKGROUND: Although antifolates are popular agents for use in chemotherapy, they display minimal toxicity against slow-growing tumors and are toxic to actively replicating cells in normal tissues. These drugs are converted intracellularly into polyglutamate derivatives by the enzyme folylpolyglutamyl synthetase (FPGS). Because tumors with high expression of FPGS often respond to nontoxic antifolate doses, we investigated whether augmenting tumoral FPGS activity by gene delivery would enhance tumoral antifolate sensitivity. METHODS: 9L rat gliosarcoma cells were stably transfected with a human FPGS complementary DNA (cDNA), producing 9L/FPGS cells. The sensitivity of these cells to the antifolates methotrexate and edatrexate was measured in culture and in subcutaneous tumors, as was their ability to increase the chemosensitivity of nearby nontransfected cells, i.e., a bystander effect. The antifolate sensitivity of nonselected cells transduced with a hybrid amplicon vector that expressed FPGS was also ascertained. RESULTS: In comparison with 9L cells, 9L/FPGS cells displayed enhanced sensitivity to 4-hour pulses of antifolate. Subcutaneous 9L/FPGS tumors responded as well to methotrexate given every third day as 9L tumors did to daily treatment. A modest bystander effect was observed with edatrexate treatment in culture and in vivo. The observed bystander effect appeared to result from the release of antifolates by transfected cells after the removal of extracellular drug. In culture, enhanced antifolate sensitivity was also seen in other stably transfected rodent and human glioma cell lines, including one with high pre-existing FPGS activity, and in canine and human glioblastoma cell lines transduced with a vector bearing FPGS cDNA. CONCLUSIONS: FPGS gene delivery enhances the antifolate sensitivity of several glioma cell lines and merits further evaluation as a therapeutic strategy. (+info)Phase I study of the sequential administration of edatrexate and paclitaxel in patients with advanced solid tumors. (3/155)
BACKGROUND: The antifolate edatrexate and the microtubule-stabilizing agent paclitaxel have both demonstrated single-agent activity in lung and breast cancer. In vitro, the sequential combination of edatrexate followed by paclitaxel produced synergistic antitumor effects. This trial was designed to find the maximum tolerated doses of edatrexate and paclitaxel when given every two weeks utilizing this sequential schedule. PATIENTS AND METHODS: Thirty-four patients with solid tumors received edatrexate intravenously on days 1 and 15 and paclitaxel intravenously as a three-hour infusion on days 2 and 16 of each 28-day cycle. Edatrexate was escalated from 40 to 120 mg/m2 and the paclitaxel dose fixed at 135 mg/m2. When the maximum-tolerated dose was not reached, edatrexate was fixed at 120 mg/m2 and paclitaxel escalated to 175 and 210 mg/m2. RESULTS: All 34 patients were assessable. The maximum tolerated doses were 120 mg/m2 of edatrexate and 210 mg/m2 of paclitaxel. Grade 3 myalgia, peripheral neuropathy, leukopenia, and an infusion-related reaction occurred. Eight patients with non-small-cell lung cancer and one with bladder cancer achieved major objective responses. CONCLUSIONS: The recommended phase II doses are 120 mg/m2 of edatrexate days 1 and 15 and 175 mg/m2 of paclitaxel as a three-hour infusion days 2 and 16 of a 28 day cycle. These results warrant phase II trials of the combination leading to phase III studies comparing the two drugs to a single agent to confirm the preclinical evidence of synergy. (+info)Dihydrofolate reductase from Kaposi's sarcoma-associated herpesvirus. (4/155)
Kaposi's sarcoma-associated herpesvirus (KSHV) is the first human virus known to encode dihydrofolate reductase (DHFR), an enzyme required for nucleotide and methionine biosynthesis. We have studied the purified KSHV-DHFR enzyme in vitro and analyzed its expression in cultured B-cell lines derived from primary effusion lymphoma (PEL), an AIDS-associated malignancy. The amino acid sequence of KSHV-DHFR is most similar to human DHFR (hDHFR), but the viral enzyme contains an additional 23 amino acids at the carboxyl-terminus. The viral DHFR, overexpressed and purified from E. coli, was catalytically active in vitro. The K(m) of KSHV-DHFR for dihydrofolate (FH(2)) was 2.4 microM, which is significantly higher than the K(m) of recombinant hDHFR (rhDHFR) for FH(2) (390 nM). K(m) values for NADPH were similar for the two enzymes, about 1 microM. KSHV-DHFR was inhibited by folate antagonists such as methotrexate (K(i): 200 pM), aminopterin (K(i): 610 pM), pyrimethamine (K(i): 29 nM), trimethoprim (K(i): 2.3 microM), and piritrexim (K(i): 3.9 nM). In all cases, K(i) values for these folate antagonists were higher for KSHV-DHFR than for rhDHFR. The viral enzyme was expressed at levels two- to tenfold higher than hDHFR in PEL cell lines as an early lytic cycle gene. KSHV-DHFR mRNA and protein appeared from 6 to 24 h after chemical induction of the KSHV lytic cycle. Epitope-tagged KSHV-DHFR and rhDHFR both localized to the nucleus of transfected cells, while other KSHV nucleotide metabolism genes localized to the cytoplasm. DHFR activity was not essential for viral replication in cultured PEL cells. Since hDHFR was not detectable in peripheral blood mononuclear cells (PBMCs), KSHV-DHFR may function to provide increased DHFR activity in vivo in infected cells that have little or none of their own enzyme. (+info)A spontaneous murine melanoma lung metastasis comprised of host x tumor hybrids. (5/155)
Cells from a lung metastasis, arising from Cloudman S91 melanoma cells implanted s.c. in the tail of a BALB/c nu/nu mouse, were comprised chiefly of host x tumor hybrids. These lung metastasis cells showed: (a) 30-40% increased DNA content; (b) resistance to 10(-4) M hypoxanthine, 4 x 10(-7) M aminopterin, and 1.6 x 10(-5) M thymidine (HAT) + G418; and (c) the presence in genomic DNA of genes for both wt and albino tyrosinase, reflecting the DBA/2J (Cloudman S91) and BALB/c mouse genotypes, respectively. Individual clones of lung metastasis cells expressed enhanced pigmentation, motility, and responsiveness to MSH/IBMX, a behavior similar to that recently reported for artificially generated melanoma x macrophage fusion hybrids. These similarities suggested that the host fusion partner generating the lung metastasis hybrids might have been a macrophage, although formal proof for this was not possible. The results provide the first direct evidence that host x tumor hybridization could serve as an initiating mechanism for melanoma metastasis. (+info)Trans-stimulation effects of folic acid derivatives on methotrexate transport by rat renal organic anion transporter, OAT-K1. (6/155)
We examined the pharmacological role of the renal organic anion transporter OAT-K1, which localizes predominantly in the brush-border membranes of proximal straight tubules, in the urinary excretion of methotrexate and the possibility of its contribution to "folinic acid rescue." With Madin-Darby canine kidney (MDCK) cells stably transfected with OAT-K1 cDNA, OAT-K1-mediated methotrexate accumulation was inhibited in the presence of various folic acid derivatives. These derivatives included aminopterin, 5-methyltetrahydrofolic acid, unlabeled methotrexate, folinic acid (citrovorum factor, leucovorin), and folic acid with apparent inhibition constant values of 0.5, 1.2, 1.8, 8.2, and 14.1 microM, respectively. In contrast, 10 microM taurocholic acid and sulfobromophthalein did not inhibit OAT-K1-mediated methotrexate accumulation. In addition, methotrexate efflux was stimulated in the presence of inwardly directed gradients of aminopterin, 5-methyltetrahydrofolic acid, unlabeled methotrexate, folinic acid, and folic acid, but not of uric acid, taurocholic acid, and glutathione, indicating that OAT-K1-mediated methotrexate efflux is stimulated by a folic acid derivatives exchange. In conclusion, OAT-K1 was suggested to enhance the apical efflux of highly accumulated methotrexate in tubular epithelial cells and contribute at least in part to folinic acid rescue by exchanging intracellular methotrexate for extracellular folinic acid. (+info)Phase I and pharmacokinetic study of 10-propargyl-10-deazaaminopterin, a new antifolate. (7/155)
The 10-deazaaminopterins are a new class of rationally designed antifolates demonstrating greater antitumor effects than methotrexate in murine tumor models and human tumor xenografts. Their design was aimed at improving membrane transport and polyglutamylation in tumor cells, resulting in increased intracellular accumulation and enhanced cytotoxicity. Compared with other 4-aminofolate analogues, 10-propargyl-10-deazaaminopterin (PDX) is the most efficient permeant for the RFC-1-mediated internalization and substrate for folylpolyglutamate synthetase. PDX demonstrates greater in vitro and in vivo antitumor efficacy than methotrexate or edatrexate. We undertook a Phase I study with PDX to identify the potential toxicities and define an optimal dose and schedule. Thirty-three patients were enrolled, all of whom had non-small cell lung cancer (NSCLC) and were treated previously with a median of two prior chemotherapy regimens. Initially, PDX was administered weekly for 3 weeks in a 4-week cycle. Mucositis requiring dose reduction and/or delay in the first cycle occurred in four of six patients treated at the initial dose level (30 mg/m2), making this the maximal tolerated dose for PDX given on this schedule. The treatment schedule was then modified to every 2 weeks. Twenty-seven patients were treated twice weekly with a total of 102 four-week cycles (median, 2 cycles/patient). Mucositis was the dose-limiting toxicity, with grade 3 and 4 mucositis occurring in the first two patients treated at the 170 mg/m2 dose level. Other toxicities were mild and reversible. No neutropenia was observed. The recommended Phase II dose is 150 mg/m2 biweekly. At that dose level, the mean area under the curve was 20.6 micromol x h, and the mean terminal half-life was 8 h. Two patients with stage IV NSCLC had major objective responses, and five patients had stable disease for 7 (two patients), 9 (one patient), 10 (one patient), and 13 months (one patient). PDX is a new antifolate with manageable toxicity and evidence of antitumor activity in NSCLC. A Phase II trial in NSCLC and a Phase I trial with paclitaxel are under way. These studies will also quantitate the expression of genes controlling internalization (RFC-1) and polyglutamylation of PDX in tumor cells as correlates of response. (+info)Co-administration of probenecid, an inhibitor of a cMOAT/MRP-like plasma membrane ATPase, greatly enhanced the efficacy of a new 10-deazaaminopterin against human solid tumors in vivo. (8/155)
Earlier studies from this laboratory have shown that the uricosuric agent probenecid (PBCD) will inhibit the extrusion of folate analogues from tumor cells mediated by a plasma membrane ATPase resembling the canicular multispecific organic anion transporter/multidrug resistance-related protein (MRP) family of ATP binding cassette transporters. This inhibition of this outwardly directed membrane ATPase has been shown to have a favorable impact upon the cellular pharmacokinetics, cytotoxicity, and efficacy of methotrexate in vivo. In an extension of these earlier studies, which had focused only on murine ascites tumors, we now report that parental co-administration of PBCD will also enhance net intracellular accumulation in vitro and intracellular persistence in vivo of a new folate analogue, 10-propargyl-10-deazaaminopterin (PDX) in tumor cells. This resulted in marked enhancement of the efficacy of PDX against murine and human lung neoplasms and human prostate and mammary neoplasms growing as solid tumors in mice. As possible ATPases targeted by PBCD, all of these tumors expressed MRP-1, -4, and -7 genes, with expression of MRP-4 being greatest in each case. Four other MRP genes were expressed to a variable extent in some tumors but not others. The therapeutic enhancement of PDX by PBCD was manifested as tumor regression, where PDX alone was only growth inhibitory (A549 NSCL tumor), or as a substantial increase (3-4-fold) in overall regression and/or number of complete regressions (Lewis and LX-1 lung, PC-3 and TSU-PR1 prostate, and MX-1 mammary tumors) compared to PDX alone. Also, only in the case of PDX with PBCD, a significant number of mice transplanted with LX-1 or MX-1 tumors that experienced complete regression did not have regrowth of their tumor. In view of these results, clinical trials of this therapeutic modality appear to be warranted, especially in the case of new more efficacious folate analogues that are also permeants for this canicular multispecific organic anion transporter/MRP-like plasma membrane ATPase. (+info)Fetal Aminopterin Syndrome
Aminopterin (4-Aminofolic acid) | Folic Acid/ DHFR Antagonist | MedChemExpress
Aminopterin - Wikipedija, prosta enciklopedija
Aminopterin - Википедија, слободна енциклопедија
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Aminopterin inhibition in Aerobacter aerogenes: alanine and valine accumulation during the inhibition and their utilization on...
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Aminopterin
... has a single-dose LDLo of 2.5 mg/kg when orally administered to rats. Aminopterin is widely used in selection media ... Aminopterin is a synthetic derivative of pterin. Aminopterin works as an enzyme inhibitor by competing for the folate binding ... and 0.097 mg/kg aminopterin each day for 7 to 12 days. Folic acid was given in a weight ratio to aminopterin of 200:1 to 800:1 ... the enzyme inhibited by aminopterin. Leucovorin has been used in rats, dogs and humans to rescue aminopterin toxicity. ...
Thymidine kinase
"Aminopterin". PubChem. U.S. National Library of Medicine. Köhler G, Milstein C (August 1975). "Continuous cultures of fused ... After fusion, the cells are grown in a medium with methotrexate or aminopterin that inhibit the enzyme dihydrofolate reductase ... One such medium that is commonly used is HAT medium, which contains hypoxanthine, aminopterin and thymidine. The unfused cells ...
Mary Jane Osborn
Osborn, M. J.; Freeman, M.; Huennekens, F. M. (February 1958). "Inhibition of dihydrofolic reductase by aminopterin and ... Inhibition of Dihydrofolic Reductase by Aminopterin and Amethopterin. DOI: 10.3181/00379727-97-23764 Wayne, Tiffany K. (2011 ...
Hybridoma technology
... hypoxanthine-aminopterin-thymidine medium) for roughly 10 to 14 days. Aminopterin blocks the pathway that allows for nucleotide ...
HAT medium
Aminopterin in the medium blocks the de novo pathway. Hence, unfused myeloma cells die, as they cannot produce nucleotides by ... HAT Medium (hypoxanthine-aminopterin-thymidine medium) is a selection medium for mammalian cell culture, which relies on the ... The trick is that aminopterin blocks DNA de novo synthesis, which is absolutely required for cell division to proceed, but ... is specifically blocked by aminopterin. THF, acting in association with specific proteins, can receive single carbon units that ...
2007 pet food recalls
Aminopterin is illegal in China, and neither Cornell University nor the FDA could replicate the New York lab's results. On 27 ... "No Aminopterin in Tissues of Animals Killed by Recalled Pet Food". PRNewsWire. March 30, 2007. Archived from the original on ... On 23 March, the New York State Food Laboratory reported that aminopterin was found in samples sent to them by Cornell. ... Beginning on 19 April, researchers reportedly had ruled out aminopterin contamination and had found a "spoke-like crystal" in ...
Timeline of the 2007 pet food recalls
The New York State Food Laboratory reported that aminopterin was found in samples sent to them by Cornell. Aminopterin is ... "No Aminopterin in Tissues of Animals Killed by Recalled Pet Food" (Press release). Syntrix Biosystems. March 30, 2007. Archived ... "fully consistent with the ingestion of rat poison containing aminopterin." The U.S. Food and Drug Administration (FDA) ...
Indian Americans
He obtained his Ph.D. the same year, and went on to make other major discoveries; including the synthesis of aminopterin (later ...
Somatic fusion
This medium is supplemented with hypoxanthine, aminopterin and thymidine, hence the name HAT medium. Antimetabolite aminopterin ... since they cannot produce purines and pyrimidines due to the aminopterin present in the HAT medium). For using HAT medium as a ...
Monoclonal antibody
Exposing cells to aminopterin (a folic acid analogue, which inhibits dihydrofolate reductase, DHFR), makes them unable to use ... The selective culture medium is called HAT medium because it contains hypoxanthine, aminopterin and thymidine. This medium is ...
Stuart A. Rice
Effect of folic acid, aminopterin and vitamin K on growth of roots in Allium cepa. Proc. Soc. Exp. Biol. Med. 74:310-12 "The ...
History of cancer chemotherapy
These analogues - first aminopterin and then amethopterin (now methotrexate) were antagonistic to folic acid, and blocked the ... and similar to aminopterin) treatment. Dr. Richard Lewisohn of Mount Sinai Hospital in New York administered the drug, and over ... Aminopterin)". New England Journal of Medicine. 238 (23): 787-793. doi:10.1056/nejm194806032382301. PMID 18860765. Retrieved ...
Yellapragada Subbarow
... aminopterin)". N. Engl. J. Med. 238 (23): 787-93. doi:10.1056/NEJM194806032382301. PMID 18860765.{{cite journal}}: CS1 maint: ...
Sidney Farber
Realizing this, he attempted to use a folate antagonist, aminopterin, to block the function of folic acid in patients with ... In 1947, Farber conducted a clinical trial on aminopterin on 16 children, 10 of which eventually achieved temporary remission. ... aminopterin)". New England Journal of Medicine. 238 (23): 787-793. doi:10.1056/nejm194806032382301. PMID 18860765.{{cite ... he carried out both the preclinical and clinical evaluation of aminopterin (synthesized by Yellapragada Subbarow). He showed ...
Birth defect
Aminopterin, a cytostatic drug with antifolate effect, was used during the 1950s and 1960s to induce therapeutic abortions. In ... some cases, the abortion did not happen, but the newborns had a fetal aminopterin syndrome consisting of growth retardation, ...
Purine nucleoside phosphorylase
Often the de novo pathway is interrupted as a result of chemotherapy drugs such as methotrexate or aminopterin. All salvage ...
The New England Journal of Medicine
His team gave 16 infants and children with acute lymphoblastic leukemia a folic acid inhibitor, aminopterin-10 showed ... Aminopterin)". New England Journal of Medicine. 238 (23): 787-93. doi:10.1056/NEJM194806032382301. PMID 18860765. Zoll, PM ( ...
Min Chiu Li
Farber was able to use a drug of this type, aminopterin, to achieve a temporary remission in childhood leukemia. In the early ...
Donald Pinkel
... experimenting with the impact of aminopterin on leukemia. Pinkel was named chief of pediatrics at Roswell Park Comprehensive ...
Leukemia
By 1947, Boston pathologist Sidney Farber believed from past experiments that aminopterin, a folic acid mimic, could ...
Folate
This research subsequently led to the synthesis of the antifolate aminopterin, which was used to treat childhood leukemia by ...
Methotrexate
In 1947, a team of researchers led by Sidney Farber showed aminopterin, a chemical analogue of folic acid developed by ... Animal studies published in 1956 showed the therapeutic index of methotrexate was better than that of aminopterin, and clinical ... use of aminopterin was thus abandoned in favor of methotrexate. In 1951, Jane C. Wright demonstrated the use of methotrexate in ...
June Biedler
In particular, the group found that L1210 sublines that were resistant to the folate analogue aminopterin (later replaced by ...
List of MeSH codes (D03)
... aminopterin MeSH D03.438.733.631.192.500 - methotrexate MeSH D03.438.733.631.202 - biopterin MeSH D03.438.733.631.202.500 - ...
Boston Children's Hospital
Yellapragada Subbarow (of Lederle lab and his friend and colleague at Harvard Medical School) to supply Aminopterin and later ... Sidney Farber received the Lasker in 1966 for his 1947 discovery that a combination of aminopterin and methotrexate, both folic ...
Dana-Farber Cancer Institute
... using aminopterin. This, and another antifolate drug, methotrexate used by Dr. Farber, were discovered and supplied by Dr. ...
Developmental toxicity
Some of the known developmental toxicants can be grouped under the following categories: Reproductive toxins: Aminopterin ...
Madras Medical College
... known for the synthesis of the first ever chemotherapeutic drug aminopterin, and subsequently methotrexate. He is also known ...
Institute of Cancer Research
David Galton became the first physician in the world to use aminopterin (the forerunner of the methotrexate drug) in the ...
Menu Foods
... aminopterin, melamine (a plastic precursor that may also be used as a fertiliser), and cyanuric acid (which is commonly used to ...
API | aminopterin
... aminopterin , aminopterine , aminopterin sodium , a-ninopterin , apga , minopterin , n-(4-{[(2,4-diamino-6-pteridinyl)methyl] ... During the period Aminopterin was marketed, the agent was used off-label to safely treat over 4,000 patients with psoriasis in ... The use of aminopterin in cancer treatment was supplanted in the 1950s by methotrexate due to the latters better therapeutic ... Aminopterin was marketed by Lederle Laboratories (Pearl River, New York) in the United States from 1953 to 1964 for the ...
Folic acid - test: MedlinePlus Medical Encyclopedia
Folate (Folic Acid): Reference Range, Interpretation, Collection and Panels
75 Years: A Look Back on Methotrexate's Fascinating History
By late January, aminopterin had brought the childs WBC count down to the realm of 12,000, just slightly above normal, with ... Testing aminopterin, beginning with young Robert Sandler at the end of December, is what proved his hypothesis correct. ... As early as the 1950s, dermatologists were using aminopterin to treat psoriasis. This led to the approval of methotrexate for ... Merely another chemical modification in a series of attempts by the research team, the new drug, aminopterin, was not expected ...
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US Patent for Methods of treatment using anti-ErbB antibody-maytansinoid conjugates Patent (Patent # 7,097,840 issued August...
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The New England Journal of Medicine - Unionpedia, the concept map
Aminopterin. Aminopterin (or 4-aminopteroic acid), the 4-amino derivative of folic acid, is an antineoplastic drug with ... New!!: The New England Journal of Medicine and Aminopterin · See more ». Amputation. Amputation is the removal of a limb by ... 63 relations: Acute lymphoblastic leukemia, Addiction Rare in Patients Treated with Narcotics, Aminopterin, Amputation, ...
MethotrexateThymidineFolic acid antagoAntagonistMaternal diabetesChemotherapiesAcute leukemiaAcidAntineoplasticSynthesisEnzymeInhibitionPoisonCancerLaboratoryDrugMethotrexateHypoxanthineFetalPyrimethamineFolic acidAlcoholAntifolateSyndromeAndrogensMethylChemotherapyHybridomasDerivativeFarberReplicationRatsCompoundMenu FoodsDiabetesDramaticCellType
Methotrexate5
- Aminopterin was discontinued by Lederle Laboratories in favor of methotrexate due to manufacturing difficulties of the former. (liu.edu)
- The use of aminopterin in cancer treatment was supplanted in the 1950s by methotrexate due to the latter's better therapeutic index in a rodent tumor model. (liu.edu)
- Now in a more pure preparation and supported by laboratory evidence of superior tumor cell uptake in vitro, aminopterin is being investigated in clinical trials in leukemia as a potentially superior antifolate to methotrexate. (liu.edu)
- To further characterize the Drosophila-based prescreen to detect developmental toxicants, the following 8 chemicals were evaluated - methyl mercury chloride (MMC), methotrexate (MTX), L-phenylalanine (LPA), sodium arsenate heptahydrate (SAH), cadmium chloride (CC), vinblastine sulfate (VBS), aminopterin (APN) and mitomycin C (MC). (cdc.gov)
- Congenital cardiac defects: a possible association of aminopterin syndrome and in utero methotrexate exposure? (cdc.gov)
Thymidine2
- Splenocytes were fused with P3U1 cells and hypoxanthine-aminopterin-thymidine selection was performed. (leinco.com)
- HAT selective medium components ( hypoxanthine, aminopterin, thymidine) are used. (modernloveok.com)
Folic acid antago1
- however, contributing factors include folic acid deficiency, anticonvulsant therapy with carbamazepine and valproic acid, antineoplastic drug therapy with aminopterin or other folic acid antagonists, antimalarial drugs, and maternal diabetes (Hansen & Warf, 2017). (nann.org)
Antagonist2
- An earlier suspect toxin was aminopterin, an antagonist of folic acid. (petplace.com)
- A pharmaceutical company had synthesized this "antagonist" to folic acid (aminopterin), and in November 1947, Farber tried the drug on 16 terminally ill children. (massmoments.org)
Maternal diabetes1
- The aminopterin, maternal diabetes, hyperther- hospital serves as a referral centre for ob- mia, low socioeconomic status, and lack of stetric and gynaecologic problems and a folate have been shown to increase the risk prenatal intensive care unit for all other of NTD. (who.int)
Chemotherapies1
- Transformative therapies have come before, with a broad spectrum of activity and durable response (eg, chemotherapies like aminopterin or cisplatin, the B-cell-targeting rituximab, among many others). (cldinc.com)
Acute leukemia1
- In the late 1940s, legendary cancer researcher Sydney Farber and colleagues reported successfully treating acute leukemia in children with a new drug called aminopterin. (statnews.com)
Acid2
- Poisonous chemicals such as "melamine," "aminopterin," and "cyanuric acid" were identified in pet food products imported from China. (kennesaw.edu)
- Aminopterin (or 4-aminopteroic acid), the 4-amino derivative of folic acid, is an antineoplastic drug with immunosuppressive properties often used in chemotherapy. (unionpedia.org)
Antineoplastic1
- Aminopterin is a synthetic derivative of pterins with antineoplastic and immunosuppressive properties. (liu.edu)
Synthesis3
- As a folate analog, aminopterin competes for the folate binding site of the enzyme dihydrofolate reductase, thereby blocking tetrahydrofolate synthesis, and resulting in depletion of nucleotide precursors and inhibition of DNA, RNA and protein synthesis. (liu.edu)
- The aminopterin found in the medium blocks the de novo DNA nucleotide synthesis pathway. (turningtooneanother.net)
- This research in the Lederley Lab, Pearl River, NY under Dr. Yellapragada Subbarao, the then Director of the institute, was the basis for synthesis of Aminopterin, the first ever anti-cancer drug, the clinical proof of its efficacy was proven by Dr. S. Farber in 1948. (news-medical.net)
Enzyme1
- medium, since the myeloma cells provide the ability to grow in animal cell culture medium and plasma cells contribute the functional HGPRT enzyme necessary to overcome the aminopterin blocks. (turningtooneanother.net)
Inhibition1
- Incubation of fused cells in the HAT medium cause aminopterin in the myeloma cells death as nucleotide inhibition occur. (modernloveok.com)
Poison1
- Menu Foods initially blamed the contamination on a chemical called Aminopterin, which is used as a rat poison and to treat cancer. (dogster.com)
Cancer1
- Director Daniel Rice said aminopterin was a cancer drug about 50 years ago in the United States. (petplace.com)
Laboratory2
- The New York State Food Laboratory reported that it found aminopterin in food from the palatability studies. (petplace.com)
- At press time, no laboratory had announced an independent confirmation of the aminopterin finding. (petplace.com)
Drug1
- Tous les résultats de la recherche seront tirés du « National Drug Schedules » du site Web en anglais. (napra.ca)
Methotrexate11
- Analogues of methotrexate and aminopterin with gamma-methylene and gamma-cyano substitution of the glutamate side chain: synthesis and in vitro biological activity. (harvard.edu)
- Aminopterin and methotrexate, which have a structure similar to that of folic acid, are used in the treatment of certain types of malignant tumors. (thefreedictionary.com)
- To further characterize the Drosophila-based prescreen to detect developmental toxicants, the following 8 chemicals were evaluated - methyl mercury chloride (MMC), methotrexate (MTX), L-phenylalanine (LPA), sodium arsenate heptahydrate (SAH), cadmium chloride (CC), vinblastine sulfate (VBS), aminopterin (APN) and mitomycin C (MC). (cdc.gov)
- Aminopterin was discontinued by Lederle Laboratories in favor of methotrexate due to manufacturing difficulties of the former. (cloudfront.net)
- The use of aminopterin in cancer treatment was supplanted in the 1950s by methotrexate due to the latter's better therapeutic index in a rodent tumor model. (cloudfront.net)
- [5] Now in a more pure preparation and supported by laboratory evidence of superior tumor cell uptake in vitro , aminopterin is being investigated in clinical trials in leukemia as a potentially superior antifolate to methotrexate. (cloudfront.net)
- [7] Similar congenital abnormalities have been documented with methotrexate, and collectively their teratogenic effects have become known as the fetal aminopterin syndrome . (cloudfront.net)
- Methotrexate is a stable derivative of aminopterin, a folate antimetabolite. (phcog.com)
- Gbs has well recognized human teratogens exposure type fetal effect drugs aminopterin methotrexate growth restriction, microcephaly, and mental health services administration, mesolimbic da system is the production of platelets could be due to very premature infants and children, have a pneumopericardium drained by needle aspiration frequently have aggressive malignancies. (umaine.edu)
- Both the enzymically active form and the isomer having the opposite configuration at carbon 6 inhibited the influx of enzymically synthesized (+)-5-methyltetrahydrofolate, methotrexate, and aminopterin. (elsevier.com)
- The most striking effect is observed with ternary complexes containing methotrexate or aminopterin and NADPH: maximal retention of the labeled protein in the immunoprecipitation assay is reduced to approximately 30% of its original value with dihydrofolate reductase alone due to a decrease in both the affinity and lifetime of the antibody-protein complex at one or more antigenic sites. (nih.gov)
Hypoxanthine6
- ClonaCell™-HY AOF Expansion Medium is an animal origin-free (AOF) and serum-free liquid medium optimized for hybridoma expansion after hypoxanthine, aminopterin, thymidine (HAT) selection. (stemcell.com)
- The medium contains hypoxanthine and thymidine (HT) and is used to wean hybridomas off aminopterin used during the selection process. (stemcell.com)
- Only myeloma cells that do not secrete antibody are used, and these cells also lack the hypoxanthine-guanine phosphoribosyltransferase (HGPRT) gene, making them sensitive to hypoxanthine-aminopterin-thymine (HAT) media that contains aminopterin that blocks DNA synthesis, and thus cell division. (labmanager.com)
- If subculturing is carried out in a medium containing hypoxanthine, aminopterin, and thymidine (i.e. (biologydiscussion.com)
- Myeloma cells are refined with 8 azaguanine to testing the susceptibility to the hypoxanthine aminopterin-thymidine (HAT) medium utilized after cell combination. (get2fiu.com)
- The cells are then cultivated in the hypoxanthine aminopterin-thymidine (HAT) medium, only the hybridoma cells develop, the rest will gradually die. (get2fiu.com)
Fetal1
- Pseudoaminopterin syndrome is a developmental anomalies syndrome that resembles the aminopterin embryopathy (see this term) without history of fetal exposure to aminopterin. (orpha.net)
Pyrimethamine1
- This prescription is additionally used to recharge folic corrosive in the body and lessen the poisonous quality caused because of the organization of folic corrosive foes, for example, aminopterin, pyrimethamine, trimethoprim, triamterene, and so forth. (gmsanjivani.com)
Folic acid3
- Soon after the discovery of folic acid in 1941, its chemical analog and antifolate, aminopterin was developed and used in rheumatoid arthritis (RA) [ 1 ]. (biomedcentral.com)
- Aminopterin (or 4-aminopteroic acid), the 4-amino derivative of folic acid , is an antineoplastic drug with immunosuppressive properties often used in chemotherapy . (cloudfront.net)
- Dr. Farber eventually demonstrated that aminopterin, a compound related to the vitamin folic acid, produced remissions in children with acute lymphoblastic leukemia (ALL). (samjeffersfoundation.org)
Alcohol1
- Alcohol, methyl mercury, aminopterin, pyriproxifene, cocaine and heroin are known causes of the condition, causing the baby's skull bones to close before their time. (hickeysolution.com)
Antifolate1
- This of import fact led to the development of the first antifolate drug, aminopterin or 4-aminopteroyl-glutamic acid. (hstreasures.com)
Syndrome2
- Aminopterin syndrome. (medscape.com)
- When a similar cluster of abnormalies appears in the absence of exposure to antifolates it is referred to as aminopterin-like syndrome without aminopterin. (cloudfront.net)
Androgens1
- Drugs such as aminopterin and Cytoxan (cancer drugs), androgens and diethylstilbesterol (hormones), and coumarin (anticoagulant drug) must be avoided. (targetwoman.com)
Methyl1
- methyl + aminopterin) + perhaps (o)x(y)- + -ate . (thefreedictionary.com)
Chemotherapy1
- A decade later, the first chemotherapy drug, 4-aminopteroic acid (aminopterin), was developed after understanding the action of folate in the body. (pasioonline.com)
Hybridomas1
- Aminopterin is widely used in selection media (such as HAT medium ) for cell culture , particularly in the development of hybridomas , which secrete monoclonal antibodies . (cloudfront.net)
Derivative1
- Aminopterin is a synthetic derivative of pterin . (cloudfront.net)
Farber1
- Merely another chemical modification in a series of attempts by the research team, the new drug, aminopterin, was not expected to do anything dramatic, but Farber and the team had come such a long way since the middle of 1947, when he'd actually done the opposite of what he was doing now. (medscape.com)
Replication2
- Our findings will give new directions to vaccines and therapies which will potentially invert these dysfunctional cells and invite them to regulate HIV-1 Aminopterin replication but also provide in "Surprise and Eliminate" HIV curative strategies. (harrisbee.org)
- Aminopterin blocked a critical chemical reaction needed for DNA replication. (samjeffersfoundation.org)
Rats2
- Menu Foods first announced that aminopterin, a chemical used to poison rats, was found in canned foods. (opednews.com)
- [10] Aminopterin has a single-dose LD Lo of 2.5 mg/kg when orally administered to rats. (cloudfront.net)
Compound1
- Tests from a New York State food laboratory pointed to a compound called aminopterin as the culprit in late March, but now the FDA is now focusing on something called melamine. (livescience.com)
Menu Foods1
- On March 23, 2007, ABC News reported [12] that aminopterin was the chemical linked to the 2007 Menu Foods pet food contamination incident . (cloudfront.net)
Diabetes2
- Effect of pitressin tannate on the diabetes insipidus induced by aminopterin in the rat. (semanticscholar.org)
- The aminopterin, maternal diabetes, hyperther- hospital serves as a referral centre for ob- mia, low socioeconomic status, and lack of stetric and gynaecologic problems and a folate have been shown to increase the risk prenatal intensive care unit for all other of NTD. (who.int)
Dramatic1
- During the period Aminopterin was marketed, the agent was used off-label to safely treat over 4,000 patients with psoriasis in the United States, producing dramatic clearing of lesions. (cloudfront.net)
Cell2
- These findings identify TIGIT as a novel marker of dysfunctional HIV-specific T Aminopterin cells and suggest TIGIT along with other checkpoint receptors may be novel curative HIV targets to reverse T cell exhaustion. (harrisbee.org)
- Launch During chronic viral attacks high antigenic tons constantly stimulate T cells resulting in progressive lack of function termed "T cell Aminopterin exhaustion" [1]. (harrisbee.org)
Type1
- Anencephaly (pronounced an-en-SEF-uh-lee ) is a more severe, but less common, type of NTD. (nih.gov)