Synonyms for folic acid antagonist in Free Thesaurus. Antonyms for folic acid antagonist. 2 synonyms for methotrexate sodium: amethopterin, methotrexate. What are synonyms for folic acid antagonist?
Looking for folic acid antagonists? Find out information about folic acid antagonists. see coenzyme coenzyme , any one of a group of relatively small organic molecules required for the catalytic function of certain enzymes. A coenzyme may... Explanation of folic acid antagonists
Dihydrofolate reductase (DHFR), a key enzyme within folate biosynthetic pathway, has been a popular drug target for over six decades. Trimethoprim (TMP) is the only FDA approved antibacterial DHFR inhibitor and remains clinically important. However, acquired resistance by point mutations and natural enzymatic insensitivity limit its use. A library of novel propargyl-linked antifolates targeting DHFR from MSRA, Candida and Klebsiella species was developed. Early lead propargyl-linked antifolates were proven potent antibacterial and antifungal agents. Much effort was placed on evaluating the metabolism properties. A strategy of incorporating crystallographic insight and experimental evaluation of structure-activity relationships (SAR) to guide new compound generation was explored to optimize the drug likeliness while maintaining high antimicrobial potency. Exciting compounds with excellent antibacterial activity (MIC = 0.02 µg/mL against MRSA), moderate metabolic stability (t1/2 = 99 min), low CYP
Folic acid antagonists definition at Dictionary.com, a free online dictionary with pronunciation, synonyms and translation. Look it up now!
Antifolates are a class of antimetabolite medications that antagonise (that is, block) the actions of folic acid (vitamin B9). Folic acids primary function in the body is as a cofactor to various methyltransferases involved in serine, methionine, thymidine and purine biosynthesis. Consequently, antifolates inhibit cell division, DNA/RNA synthesis and repair and protein synthesis. Some such as proguanil, pyrimethamine and trimethoprim selectively inhibit folates actions in microbial organisms such as bacteria, protozoa and fungi. The majority of antifolates work by inhibiting dihydrofolate reductase (DHFR). Many are primarily DHFR inhibitors, but raltitrexed is an inhibitor of thymidylate synthase, and pemetrexed inhibits both and a third enzyme. Antifolates act specifically during DNA and RNA synthesis, and thus are cytotoxic during the S-phase of the cell cycle. Thus, they have a greater toxic effect on rapidly dividing cells (such as malignant and myeloid cells, and GI & oral mucosa), which ...
Although trimethoprim (TMP); (1) has been in the public domain since 1959 (H itchings and R oth1959) and available to the public since 1968 in combination with sulfamethoxazole as a broad spectrum...
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Drs. Takimoto and Allegra present a comprehensive overview of the development of antifolates over the past decade and a half. The antifolates are antimetabolite antineoplastic agents that are structurally and chemically similar to naturally occurring folates required for the synthesis of purines and pyrimidines. These drugs interfere with DNA synthesis by inhibiting key
3QLR: Crystal Structures of Candida albicans Dihydrofolate Reductase Bound to Propargyl-Linked Antifolates Reveal the Flexibility of Active Site Loop Residues Critical for Ligand Potency and Selectivity.
... Question # 1 (Multiple Answer) Antimalarials: dihydrofolate reductase inhibitors A) chloroquine (Aralen) B) chloroguanide C) pyrimethamine (Daraprim) D) trimethoprim (generic)
In the development of antimalarial agents there have been important and unresolved questions regarding the targets and mechanisms of action of two compounds presumed to affect the folate pathway. For both of these compounds, WR99210 and proguanil, various lines of evidence have suggested the chemotherapeutic action was directed against one or more targets independent of the DHFR enzyme. Using the DHFR inhibitor MTX, we have selected transformed lines of P. falciparum in which the parasite DHFR activity is supplemented by a MTX-resistant human DHFR. Transformed parasites showed a 4,000-fold increase in resistance to both MTX and WR99210. This result demonstrates that the action of WR99210 must be against parasite DHFR and is consistent with previous data indicating the excellent therapeutic window of this drug (37). Significant inhibition of a second target in P. falciparum by WR99210 is not supported by these results.. WR99210 shows no cross-resistance with pyrimethamine or cycloguanil (refs. 10 ...
Pralatrexate is given as an infusion into your vein over 3 to 5 minutes under the supervision of your doctor or nurse. Pralatrexate is usually given once a week for 6 weeks, with no treatment on the 7th week to complete the 7-week cycle. Several treatment cycles of pralatrexate may be given depending on your response to treatment. Prior to being given pralatrexate, your doctor will advise you to take certain medicines or vitamin supplements before starting and while being on treatment to help minimise side effects.. Pralatrexate is approved by the TGA for the following indication:. The treatment of adult patients with peripheral T-cell lymphoma (nodal, extranodal, and leukaemic/disseminated) who have progressed after at least one prior therapy.. Pralatrexate is listed on the PBS from April 1st, 2018. Breaking News. Pralatrexate may have the following side effects:. ...
1LY4: Analysis of quinazoline and PYRIDO[2,3D]PYRIMIDINE N9-C10 reversed bridge antifolates in complex with NADP+ and Pneumocystis carinii dihydrofolate reductase
The need for new antimicrobials is great in face of a growing pool of resistant pathogenic organisms. This review will address the potential for antimicrobial therapy based on polypharmacological activities within the currently utilized bacterial biosynthetic folate pathway. The folate metabolic pathway leads to synthesis of required precursors for cellular function and contains a critical node, dihydrofolate reductase (DHFR), which is shared between prokaryotes and eukaryotes. The DHFR enzyme is currently targeted by methotrexate in anti-cancer therapies, by trimethoprim for antibacterial uses, and by pyrimethamine for anti-protozoal applications. An additional anti-folate target is dihyropteroate synthase (DHPS), which is unique to prokaryotes as they cannot acquire folate through dietary means. It has been demonstrated as a primary target for the longest standing antibiotic class, the sulfonamides, which act synergistically with DHFR inhibitors. Investigations have revealed most DHPS enzymes
... is a condition affecting babies whose mothers were exposed to the chemical aminopterin or methotraxate during pregnancy. Only about 50 cases have been reported. Babies exposed to aminopterin or methotraxate during development can be born with developmental delays such as inability to properly grow, abnormal arms or legs, and changes to the face or skull. Symptoms of fetal aminopterin syndrome depend on how early in pregnancy the woman is exposed to aminopterin or methotraxate and the dosage of the medication being used. There is no cure for fetal aminopterin syndrome, though symptoms can be managed. Aminopterin is no longer used, but methotraxate may still be used to treat some conditions such as cancer. Pregnant women should consult a physician before taking medications with either chemical ...
Synonyms for antifolate in Free Thesaurus. Antonyms for antifolate. 6 synonyms for folic acid: folacin, folate, pteroylglutamic acid, pteroylmonoglutamic acid, vitamin Bc, vitamin M. What are synonyms for antifolate?
PRIMARY OBJECTIVES:. I. To determine the overall response rate in patients with advanced esophago-gastric cancer (EGC) to combination pralatrexate and oxaliplatin.. SECONDARY OBJECTIVES:. I. To examine the toxicity and tolerability of this regimen. II. To determine the time-to-progression and overall survival using this regimen.. III. To examine whether functionally relevant polymorphisms of genes of the folate metabolism pathway correlate with efficacy and toxicity of pralatrexate.. IV. To examine whether response to pralatrexate can be predicted by micro-ribonucleic acid (microRNA) expression profiling of the epithelial component of the tumor.. OUTLINE:. Patients receive pralatrexate intravenously (IV) over 3-5 minutes and oxaliplatin IV over 2 hours on day 1. Courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity. Oxaliplatin will be discontinued after 12 courses.. After completion of study treatment, patients are followed up for 30 days and then ...
PRIMARY OBJECTIVES:. I. To determine the overall response rate in patients with advanced esophago-gastric cancer (EGC) to combination pralatrexate and oxaliplatin.. SECONDARY OBJECTIVES:. I. To examine the toxicity and tolerability of this regimen. II. To determine the time-to-progression and overall survival using this regimen.. III. To examine whether functionally relevant polymorphisms of genes of the folate metabolism pathway correlate with efficacy and toxicity of pralatrexate.. IV. To examine whether response to pralatrexate can be predicted by micro-ribonucleic acid (microRNA) expression profiling of the epithelial component of the tumor.. OUTLINE:. Patients receive pralatrexate intravenously (IV) over 3-5 minutes and oxaliplatin IV over 2 hours on day 1. Courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity. Oxaliplatin will be discontinued after 12 courses.. After completion of study treatment, patients are followed up for 30 days and then ...
Dihydrofolate Reductase Antibodies multi-assay validated. Browse our Dihydrofolate Reductase antibody catalog backed by our 100% Guarantee.
Levoleucovorin is indicated for use as rescue therapy following high-dose methotrexate in the treatment of osteosarcoma or for diminishing the toxicity associated with inadvertent overdosage of folic acid antagonists. Levoleucovorin, as the product Fusilev (FDA, dosed at one-half the usual dose of racemic d,l-leucovorin), has an additional indication for use in combination chemotherapy with 5-fluorouracil in the palliative treatment of patients with advanced metastatic colorectal cancer (although they should not be mixed in the same infusion as a precipitate may form ...
Inhibitor dihidrofolat reduktaze (DHFR inhibitor) je molekul koji inhibira funkciju dihdrofolatne reduktaze. Molekuli ove grupe se ubrajaju u antifolate. Podatak da je folat neophodan za brzu deobu ćelija radi formiranje timina se koristi kao osnova terapeutskog pristupa. Na primer, metotreksat se koristi u hemoterapiji raka zato što može da spreči deobu neoplastičnih ćelija.[1][2] Bakterijama je takođe neophodan DHFR enzim za rast i razmonožavanje, te su inhibitori sa selektivnošću za bakterijki DHFR našli primenu kao antibakterijski agensi.[3] Više raličitih lekova deluje putem inhibicije dihidrofolatne reduktaze: ...
Ovaj lek je otkrio Dr. Yellapragada Subbarao, a prvi je koristio njegovu antifolatnu aktivnost Sidni Farber 1947. da indukuje remisiju kod dece sa leukemijom.[3][4] Aminopterin je kasnije prodavala kompanija Lederle Laboratories (Pearl River, Njujork) u SAD od 1953 do 1964 za pedijatrijsku leukemiju. Ta kompanije je u toku istog perioda prodavala blisko srodni antifolat metotreksat. Lederle Laboratories je zatim obustavila prodaju aminopterina u korist metotreksata zbog proizvodnih razloga. Aminopterin je u toku svog tržišnog veka korišćen i za tretman psorijaze u SAD. Ovaj lek je doveo do dramatičnog čišćenja lezija.[5]. Upotreba aminopterina u tretmanu raka je zamenjena 1950-tih godina metotreksatom zbog boljeg terapeutskog indeksa metotreksata.[6] Nedavno je došlo do obnavljanja interesa u aminopterin, tako da su u toku klinička ispitivanja sa ciljom suzbijanja leukemije.[7]. Ovo jedinjenje je bilo istraženo kao abortifacijent 1960-tih i ranije, ali je bilo asocirano sa ...
Aminopterin (4-aminopterojska kislina) je 4-amino derivat folne kisline, ki izkazuje imunosupresivno in citostatično delovanje. Aminopterin je sintezni derivat pterina. Deluje kot encimski zaviralec, ker se veže na vezišča encima dihidrofolat reduktaze (namesto fiziološkega substrata - folne kisline) in s tem zavre sintezo tetrahidrofolata. Posledično pride do motenj nastajanja nukleotidov in s tem do zaviranja sinteze DNK, RNK in beljakovin. Aminopterin se je nekoč uporabljal za zdravljenje raka, dandanes pa ga je povsem nadomestil metotreksat, ki je spojina s podobno strukturo. Ponekod se še vedno uporablja kot rodenticid. Leta 2007 se je v ZDA pojavil škandal z aminopterinom, ko so v okoli 100 vrst hrane za pse in mačke dokazali znatne količine spojine (nad 40 ppm). Hrano so umaknili iz prodaje. Aminopteridina pri živih živalih ni mogoče dokazati. Obstajajo sumi na nefrotoksično delovanje (strupen učinek na ledvice), vendar nedvomnih dokazov o njegovem delovanju na zdravje ...
General : Outside of a well-designed clinical study, ZINOTECAN Injection should not be used in combination with the "Mayo Clinic" regimen of 5-FU/LV (administration for 4-5 consecutive days every 4 weeks) because of reports of increased toxicity, including toxic deaths. Irinotecan should be used as recommended (see In patients receiving either Irinotecan/5-FU/LV or 5-FU/LV in the clinical trials, higher rates of hospitalization, neutropenic fever, thromboembolism, first-cycle treatment discontinuation, and early deaths were observed in patients with a baseline performance status of 2 than in patients with a baseline performance status of 0 or 1.. Diarrhea : Irinotecan can induce both early and late forms of diarrhea that appear to be mediated by different mechanisms. Early diarrhea (occurring during or shortly after infusion of Irinotecan) is cholinergic in nature. It is usually transient and only infrequently is severe. It may be accompanied by symptoms of rhinitis, increased salivation, ...
95693-76-8 - ZUQBAQVRAURMCL-CVRLYYSRSA-N - Lometrexol - Similar structures search, synonyms, formulas, resource links, and other chemical information.
OVI 237 (formerly OSI 7904L), a benzoquinazoline folate analogue, is a liposomal formulation of a thymidylate synthase inhibitor, GW 1843. OSI Oncology (the
Four folate analogues, methotrexate, aminopterin, 10-deazaaminopterin, and 10-ethyl-10-deazaaminopterin were assessed for their ability to be metabolized to poly-γ-glutamyl derivatives in three tumor lines which vary in their sensitivity to these agents. Cytotoxicity of the four analogues against the murine L1210 leukemia and the human Manca B cell leukemia, as determined by a 3-h clonogenic assay, showed aminopterin and the two 10-deazaaminopterin compounds to be approximately equivalent for each cell type and were 3- to 10- (L1210) and 7- to 14-fold (Manca) more potent than methotrexate. In murine Sarcoma 180 cells, 10-ethyl-10-deazaaminopterin and aminopterin were similarly potent but were 5- to 10-fold more potent than 10-deazaaminopterin and 40- to 80-fold more potent than methotrexate. These results could be explained in part by the differences in transport properties and substrate activities for polyglutamylation for each analogue in these cell types.. Initial rates of polyglutamate ...
The folate antagonist methotrexate (MTX) is the anchor-drug in the treatment of patients with rheumatoid arthritis (RA) [1]. The main target of MTX in intracellular folate metabolism is dihydrofolate reductase (DHFR) but several other targets have been described (e.g. thymidylate synthase [TS] and 5-amino-imidazole-4-carboxamide ribonucleotide [AICAR]). At present the exact mechanism of action of MTX in RA still remains elusive [1]. Despite the potent anti-rheumatic capacity of MTX many patients (at least 50%) become resistant to MTX during long-lasting therapy. However, little is known about the mechanisms of resistance against MTX in RA patients [2].. From the field of oncology, where MTX is used against haematological malignancies, new anti-folate drugs were developed to circumvent MTX resistance [3]. These new folate antagonists have the following characteristics: are better transported through the reduced folate carrier, are retained intracellular more efficiently by polyglutamylation via ...
So my dad has NSCLC type adenocarcinoma. He has had 5 rounds of chemo with Carboplatin and Alimta. I just read that "ALIMTA is a chemotherapy drug used to treat certain kinds of non-small cell lung cancer (NSCLC) called advanced nonsquamous NSCLC." This is from the Alimta website (alimta.com). Now I am confused as to why my dad is on Alimta if its for nonsquamous type. Anyone else with adenocarcinoma been on Alimta? My dad is going to begin maintenance therapy with avastin but I was wondering if I should ask the doctor if there is other types of chemo we should try before going to maintenance therapy? Any thoughts?. Thanks in advance! ...
Pemetrexed - Oncology Drug Information Alimta is a novel antifolate compound with inhibitory activity against a number of enzymes including thymidilate synthase, dihydrofolate reductase and glycinamide ribonucleotide formyl transferase. Alimta has been studied with cis-platinum (Cisplatin) or gemcitabine (Gemzarâ) in the treatment of non-small-cell lung cancer (NSCLC). Phase II.... Read More ...
Levoleucovorin is indicated for use as rescue therapy following high-dose methotrexate in the treatment of osteosarcoma or for diminishing the toxicity associated with inadvertent overdosage of folic acid antagonists. Levoleucovorin, as the product Fusilev (FDA, dosed at one-half the usual dose of racemic d,l-leucovorin), has an additional indication for use in combination chemotherapy with 5-fluorouracil in the palliative treatment of patients with advanced metastatic colorectal cancer (although they should not be mixed in the same infusion as a precipitate may form ...
Bifunctional dihydrofolate reductase-thymidylate synthase; Bifunctional enzyme. Involved in de novo dTMP biosynthesis. Key enzyme in folate metabolism. Can play two different roles depending on the source of dihydrofolate- de novo synthesis of tetrahydrofolate or recycling of the dihydrofolate released as one of the end products of the TS catalyzed reaction. Catalyzes an essential reaction for de novo glycine and purine synthesis, DNA precursor synthesis, and for the conversion of dUMP to dTMP (By similarity) (568 aa ...
E. Piall, N. Curtin, W. Aherne, A. Harris, V. Marks; The Quantification of 2′-Deoxyuridine 5′-Triphosphate in Anti-Folate Treated Cells using a Sensitive Radioimmunoassay. Clin Sci (Lond) 1 January 1987; 73 (s17): 18P. doi: https://doi.org/10.1042/cs073018Pa. Download citation file:. ...
Motif chief executive Graham Lumsden told investors: "Resistance to antibiotics is a major global health threat and we believe that iclaprim, a novel antibiotic in the under-utilized dihydrofolate reductase inhibitor class, can become an integral part of hospital doctors life-saving treatment strategies." ...
The appearance of electrophoretically separable isozyme patterns is specific both to type of tissue and to its stage of development (Markert & Møller, 1959). In abnormally developing embryonic systems there are alterations in the time of initial appearance and the persistence of isozymes from a variety of metabolic areas (Johnson & Spinuzzi, 1966, 1968). In malformed embryos from folic-aciddeficient rats the altered zymogram patterns of esterases from abnormal limbs were different from those of abnormal kidneys, yet differentiation of zymograms from the normal hearts of these embryos was unaltered. This implies a correlation between altered tissue-specific zymogram patterns and abnormally developing systems, though no causal relationship has as yet been shown (Johnson, 1968). Moreover, when tibial hemimelia in the rat was elicited by two different teratogens-a folic acid antagonist, 9-methylpteryol-glutamic acid (PGA), and the alkylating agent N-nitroso-N-methylurea (NNMU)-there were similar ...
In recent years, efforts are being made to search for new molecules from the natural sources and in this endeavour diaryl heptanoids, oxygenated abietanes, diterpene quinones are showing promise as new lead molecules. Randomly designed heterocyclic ionone like molecules [Anzaldi M., Sottofattori E., Rizzetto R, di Casaleto B. G., Balbi A., Eur. J. Med. Chem. (1999), 34, 837] and some novel terpenyl 2, 4-diamino pyrimidines [Rosowsky A., Papoulis A. T., Queener S. F., J. Heterocyclic Chem.(1999), 36 723] are showing promising antimicrobial and dihydrofolate reductase inhibitory activities. Rationally designed 2, 4-diaminopyrimidines and some computer aided molecules are also giving further inputs in the leishmanial dihydrofolate reductase activity. In continuation of our studies on terpenyl pyrimidines as novel antileishmanial agents [Pandey S, Suryawanshi S. N., Gupta S, Srivastava V. M. L., Eur. J. Med. Chem. (2004), 39, 969], we have designed novel terpenyl Isooxazoles for their in-vivo ...
BioAssay record AID 57587 submitted by ChEMBL: Negative logarithm of inhibition constant (-log Ki) against Dihydrofolate reductase in Escherichia coli.
Since the demonstration, in 1935, of the striking antibacterial activity of sulfanilamide, the molecule has been drastically altered in many ways.
Dihydrofolate reductase (DHFR) is a member of the reductase enzyme family, which is ubiquitously expressed in all organisms. Levels of this enzyme peak at the G1/S cell cycle boundary. Autoregulation, through DHFR-RNA interactions, has also been reported. DHFR catalyzes the NADPH dependent reduction of dihydrofolate (DHF) to tetrahydrofolate (THF) needed for several one-carbon transfer reactions in purine and pyrimidine synthesis (Jensen et al 1997, Klon et al 2002). It is also the only enzyme that reduces folic acid, a synthetic vitamin not found in nature, to dihydrofolate (Banka et al. 2011). Reduction of DHFR enzymatic activity diminishes the THF pool inside the cell which slows DNA synthesis and cell proliferation eventually leading to cell death (Assaraf et al 2007, Klon et al 2002, Morales et al 2009). DHFR inhibition is essential to the action of antifolate medications used to treat cancer and some inflammatory diseases. Changes in DHFR expression can affect susceptibility to a variety ...
For analysis of non-volatile samples, simply dispense samples into the LumaPlate-96 wells, dry down and count on TopCount®. The LumaPlate™?s solid scintillator simplifies single and dual label CPM/DPM counting by eliminating variable chemical quench and in addition dramatically reduces total cost per sample. LumaPlates™-96 are particulary suitable for low-volume samples produced from 51Cr release assays, enzyme inhibition assays, organic extractions, chromatography fractions, and capillary electrophoresis fractions.. Features & Benefits:. ...
Alimta infusion contains the active ingredient pemetrexed disodium, which is a type of chemotherapy medicine for cancer called a cytotoxic antimetabolite.
Learn about Neutrexin (Trimetrexate Glucuronate Inj) may treat, uses, dosage, side effects, drug interactions, warnings, patient labeling, reviews, and related medications.
Learn about the potential side effects of Folotyn (pralatrexate). Includes common and rare side effects information for consumers and healthcare professionals.
Sigma-Aldrich offers Aldrich-364231, 2,6-Diamino-4-chloropyrimidine 1-oxide for your research needs. Find product specific information including CAS, MSDS, protocols and references.
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The first chapter of this thesis encompasses progress towards the X-ray structure determination and drug design for the dihydrofolate reductase-thymidylate synthase (DHFR-TS) enzyme from the protozoa Toxoplasma gondii, along with another mutant construct of this protein. Solving the structure of the mutant construct, along with wildtype Tg DHFR-TS, will help elucidate both the nature of pyrimethamine resistance and inhibitor selectivity. In addition to being an excellent model for malarial resistance, T. gondii is a pathogen infecting 50% of the worlds population. T. gondii is an HIV opportunistic infection. In protozoa, DHFR-TS is a bifunctional enzyme, but in humans, DHFR and TS are separate monofunctional enzymes. The difference in connectivity makes DHFR-TS an excellent target for pathogen-specific drugs. Another important factor making DHFR-TS a good drug target is that the enzyme catalyzes reactions that are essential to all life, two sequential reactions in DNA nucleotide synthesis. ...
The chaperonin GroEL binds non-native polypeptides in an open ring via hydrophobic contacts and then, after ATP and GroES binding to the same ring as polypeptide, mediates productive folding in the now hydrophilic, encapsulated cis chamber. The nature of the folding reaction in the cis cavity remains poorly understood. In particular, it is unclear whether polypeptides take the same route to the native state in this cavity as they do when folding spontaneously free in solution. Here, we have addressed this question by using NMR measurements of the time course of acquisition of amide proton exchange protection of human dihydrofolate reductase (DHFR) during folding in the presence of methotrexate and ATP either free in solution or inside the stable cavity formed between a single ring variant of GroEL, SR1, and GroES. Recovery of DHFR refolded by the SR1/GroES-mediated reaction is 2-fold higher than in the spontaneous reaction. Nevertheless, DHFR folding was found to proceed by the same trajectories ...
Aminopterin (4-Aminofolic acid), the 4-amino derivative of folic acid, is a folic acid antagonist. Aminopterin catalyses the reduction of folic acid to tetrahydrofolic acid, and competitively inhibits dihydrofolate reductase (DHFR) with a Ki of 3.7 pM. Aminopterin has anticancer and immunosuppressive activity. Aminopterin is used in treatment of pediatric leukemia. - Mechanism of Action & Protocol.
Looking for online definition of pralatrexate in the Medical Dictionary? pralatrexate explanation free. What is pralatrexate? Meaning of pralatrexate medical term. What does pralatrexate mean?