Aminopterin
(Synonyms: 氨基蝶呤; 4-Aminofolic acid; APGA) 目录号 : GC42789
A synthetic folic acid derivative
Cas No.:54-62-6
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Aminopterin is a synthetic folic acid derivative whose metabolite is a competitive inhibitor of dihydrofolate reductase, which is a cofactor for nucleic acid synthesis. Aminopterin has anticancer and immunosuppressive properties. Formulations containing it have been used for pediatric leukemia though methotrexate is now more commonly used due to a more favorable therapeutic index. Aminopterin is a component of the widely used HAT (hypoxanthine-aminopterin-thymidine) medium to select cells for mammalian cell culture.
| Cas No. | 54-62-6 | SDF | |
| 别名 | 氨基蝶呤; 4-Aminofolic acid; APGA | ||
| Canonical SMILES | NC1=NC2=NC=C(CNC3=CC=C(C(N[C@H](C(O)=O)CCC(O)=O)=O)C=C3)N=C2C(N)=N1 | ||
| 分子式 | C19H20N8O5 | 分子量 | 440.4 |
| 溶解度 | DMSO : 14.71 mg/mL (33.40 mM; Need ultrasonic); H2O : 5 mg/mL (11.35 mM; ultrasonic and adjust pH to 8 with NaOH) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.2707 mL | 11.3533 mL | 22.7066 mL |
| 5 mM | 0.4541 mL | 2.2707 mL | 4.5413 mL |
| 10 mM | 0.2271 mL | 1.1353 mL | 2.2707 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
The photodecomposition of Aminopterin
J Immunol Methods 1987 Jul 16;101(1):141-5.PMID:3611791DOI:10.1016/0022-1759(87)90227-4.
Aminopterin is used in cell fusion experiments to select for hybrid cells by killing unfused cells which are deficient in enzymes for nucleotide salvage pathways. Aqueous Aminopterin solutions exposed to fluorescent room light (wavelength greater than 300 nm) were found to lose cytotoxicity. Inactivation was accompanied by changes in the ultraviolet absorption spectra of the solutions. The ultraviolet spectrum of an irradiated Aminopterin solution is used to provide a quantitative measure of its cytotoxicity. Aminopterin appears to be photolytically cleaved at the C9-N10 methylene-anilino bond in a reaction analogous to that known for the photolysis of folic acid irradiated at 365 nm (Lowry et al., 1949).
Enhanced polyglutamylation of Aminopterin relative to methotrexate in the Ehrlich ascites tumor cell in vitro
Cancer Res 1985 Mar;45(3):1073-8.PMID:2578870doi
The polyglutamylation of Aminopterin and methotrexate (N10-methylaminopterin) was compared in the Ehrlich ascites tumor in vitro. Three poly-gamma-glutamyl conjugates of methotrexate and Aminopterin were detected, although at an equal (1 microM) extracellular drug concentration, the net accumulation of Aminopterin polyglutamates exceeded that for the methotrexate polyglutamyl derivatives by a factor of 9. When compensation was made for transport differences between these compounds by adjusting the extracellular drug concentrations to achieve equivalent intracellular monoglutamyl substrate levels, the polyglutamylation of Aminopterin was still 2.8-fold greater than that for methotrexate, suggesting that Aminopterin is a better substrate for the folylpolyglutamate synthetase as well as the transport carrier. An additional metabolite of Aminopterin was detected within seconds following drug exposure. This derivative did not bind tightly to dihydrofolate reductase, yet it was rapidly converted to a polyglutamate. The formation of both Aminopterin polyglutamates and these novel derivatives was enhanced by increases in the free intracellular level of Aminopterin. Aminopterin polyglutamates were bound tightly to dihydrofolate reductase and were retained intracellularly relative to unaltered Aminopterin when Ehrlich cells containing these forms were suspended in drug-free medium. These findings support a role for the polyglutamylation of Aminopterin as a critical element in drug action and as a factor in addition to membrane transport in the disparate antifolate potencies of Aminopterin and methotrexate.
Effect of "Aminopterin" on epithelial tissues
Arch Dermatol 1983 Jun;119(6):513-24.PMID:6859892doi
The folic acid antagonist, 4-aminopteroyl glutamic acid ("Aminopterin"), is a potent inhibitor of growth and of connective tissue proliferation. The present study indicates that the suppressive effects of "Aminopterin" on epithelial structures are more striking than on connective tissue, as revealed by observation of interference with wound healing and epithelization, atrophy and ulceration of mucosa, alopecia, and prompt suppressive effects in such dermatologic disorders as psoriasis and chronic indurative dermatoses. "Aminopterin" was administered orally in daily doses of 1.5 to 2.0 mg. to thirteen patients with psoriasis (of whom six had associated arthritis) and to five patients with chronic indurative dermatoses. The latter included one patient with chronic atopic eczematoid dermatitis with associated asthma, one with chronic eczematoid seborrheic dermatitis, one with chronic discoid lupus erythematosus involving the face, and two with scleroderma. In all patients there were remissions in cutaneous lesions, which appeared most commonly between the 5th and 10th day of "Aminopterin" therapy. Treatment was interrupted in most patients after an initial course of 14 to 28 mg. because of the regular occurrence of shallow ulceration of the buccal mucosa and frequent development of abdominal cramps. Remissions persisted for periods ranging from two weeks to several months, after which lesions returned which responded to further courses of "Aminopterin." The therapeutic response was more complete in the seven patients with psoriatic arthritis than in in six subjects with uncomplicated psoriasis. In four patients with psoriatic arthritis in whom the responses to "Aminopterin" and cortisone were compared, arthritic manifestations were considerably more relieved by cortisone, but improvement in psoriasis was consistently more complete and more sustained with "Aminopterin." No evidence of a summative effect of cortisone and "Aminopterin" on psoriasis was observed when the two were employed concomitantly, although amelioration of arthritic symptoms was more complete than when cortisone was given alone. Topical application of "Aminopterin" in a 1% ointment was found to be ineffective. "Aminopterin" is a toxic drug, and its administration must be carefully supervised. The citrovorum factor has proved useful in overcoming "Aminopterin" toxicity but interferes with its therapeutic effects. It is suggested that "Aminopterin" may prove useful in other dermatologic disorders and in cutaneous manifestations of some systemic diseases which, in certain instances, have been temporarily benefited by cortisone.
Phase II trial of oral Aminopterin for adults and children with refractory acute leukemia
Clin Cancer Res 2005 Nov 15;11(22):8089-96.PMID:16299240DOI:10.1158/1078-0432.CCR-05-0355.
Purpose: To determine the antileukemic activity of weekly oral Aminopterin in patients with refractory acute leukemia; to describe the pharmacodynamic properties of Aminopterin; and to contrast the intracellular metabolism of Aminopterin and methotrexate by patients' blasts in vitro. Experimental design: Forty-six patients were enrolled in three strata: children with acute lymphoblastic leukemia (ALL), adults with ALL, and patients with acute myeloid leukemia (AML). Aminopterin was given weekly, in two doses of 2 mg/m(2), 12 hours apart. Limited sampling pharmacokinetic analysis was done during the first week of therapy. Accumulation of [(3)H]Aminopterin and [(3)H]methotrexate by leukemic blasts was studied in vitro. Results: Six of 22 children with ALL (27%; 95% confidence interval, 8-47%) had clinically significant responses. None of those with AML and only two of 11 adults with ALL had responses meeting protocol definitions, although peripheral blast counts tended to decrease with therapy in all groups. Mucosal toxicity was minimal, even with limited use of leucovorin rescue. Complete bioavailability of Aminopterin was confirmed, with a mean area under the curve of 0.52 +/- 0.03 micromol hour/L after oral dosing. No relationship between Aminopterin pharmacokinetics and response was seen. In vitro, Aminopterin showed more consistent metabolism by leukemic blasts to polyglutamates than methotrexate. Lineage-specific differences in the pattern of intracellular antifolylpolyglutamates were observed. Conclusions: Weekly oral Aminopterin has significant activity among children with refractory ALL. With greater cellular accumulation and metabolism, more reliable bioavailability than methotrexate, and tolerable toxicity at this dose and schedule, Aminopterin deserves further study as a potent alternative to methotrexate.
Methotrexate and Aminopterin lack in vivo antimalarial activity against murine malaria species
Exp Parasitol 2009 Oct;123(2):118-21.PMID:19527714DOI:10.1016/j.exppara.2009.06.007.
The antifolate anticancer drug methotrexate (MTX) has potent activity against Plasmodium falciparum in vitro. Experience of its use in the treatment of rheumatoid arthritis indicates that it could be safe and efficacious for treating malaria. We sought to establish a murine malaria model to study the mechanism of action and resistance of MTX and its analogue Aminopterin (AMP). We used Plasmodium berghei, Plasmodium yoelii yoelii, Plasmodium chabaudi and Plasmodium vinckei. None of these species were susceptible to either drug. We have also tested the efficacy of pyrimethamine in combination with folic acid in P. berghei, and data indicate that folic acid does not influence pyrimethamine efficacy, which suggests that P. berghei may not transport folate. Since MTX and AMP utilise folate receptor/transport to gain access to cells, their lack of efficacy against the four tested murine malaria species may be the result of inefficiency of drug transport.