Dihydrofolic acid
(Synonyms: 二氢叶酸) 目录号 : GC33603An active metabolite of folic acid
Cas No.:4033-27-6
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >90.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Dihydrofolic acid is an active metabolite of folic acid and an intermediate in the biosynthesis of both purines and pyrimidines.1,2 It is formed via the NADH-dependent reduction of folic acid by dihydrofolate reductase (DHFR).2 Dihydrofolic acid (10, 50, and 100 ?g/ml) reduces insulin-like growth factor 1 receptor (IGF-1R) promotor activity in a cell-based reporter assay.3
1.Futterman, S.Enzymatic reduction of folic acid and dihydrofolic acid to tetrahydrofolic acidJ. Biol. Chem.228(2)1031-1038(1957) 2.López, C.A., and Menendez, J.C.AntimetabolitesMedicinal Chemistry of Anticancer Drugs9-52(2008) 3.Attias, Z., Werner, H., and Vaisman, N.Folic acid and its metabolites modulate IGF-I receptor gene expression in colon cancer cells in a p53-dependent mannerEndocr. Relat. Cancer13(2)571-581(2006)
| Cas No. | 4033-27-6 | SDF | |
| 别名 | 二氢叶酸 | ||
| Canonical SMILES | O=C(O)CC[C@@H](C(O)=O)NC(C1=CC=C(NCC2=NC3=C(N=C(N)NC3=O)NC2)C=C1)=O | ||
| 分子式 | C19H21N7O6 | 分子量 | 443.41 |
| 溶解度 | DMF: 1 mg/ml,DMSO: 5 mg/ml | 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 | 2.2552 mL | 11.2762 mL | 22.5525 mL |
| 5 mM | 0.451 mL | 2.2552 mL | 4.5105 mL |
| 10 mM | 0.2255 mL | 1.1276 mL | 2.2552 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。
Isolation and characterization of Dihydrofolic acid reductase from methotrexate-sensitive and -resistant human cell lines
J Biol Chem 1981 Oct 10;256(19):10169-75.PMID:7275974doi
Dihydrofolic acid reductase has been purified by affinity chromatography to apparent homogeneity from the human HeLa BU-25 cell line and from two methotrexate-resistant variants, one deriving from HeLa BU-25 and the other from the human VA2-B cell line. The purified enzymes from the three sources have been characterized in their physical and enzymatic properties. They were not found to differ significantly as concerns their electrophoretic mobility in polyacrylamide gels under a variety of conditions, their specific Dihydrofolic acid reductase and folic acid reductase activities, their Km values for folic acid and TPNH, their sensitivity to methotrexate, and the pH dependence of their folic acid reductase activity. The human Dihydrofolic acid reductase has an apparent molecular weight of 21,000 to 22,000, a Km for folic acid of 6.1 to 7.6 X 10(-6) M and a Km for TPNH of 1.6 to 1.7 X 10(-4) M, turnover numbers of about 500 and 65 mol/min/mol of enzyme for the Dihydrofolic acid reductase and the folic acid reductase activity, respectively. The values of the above mentioned physical and kinetic parameters are comparable to those reported for the Dihydrofolic acid reductase from other animal cell systems. The Dihydrofolic acid reductase content of the two-resistant cell lines is at least 200-fold higher than that of the methotrexate-sensitive HeLa BU-25 cell line. The available evidence indicates that this increased Dihydrofolic acid reductase content results from a hyperproduction of an enzyme identical or similar to that of the sensitive cells, presumably due to a selective Dihydrofolic acid reductase gene amplification, as previously reported for other cell lines of rodent origin.
Acidic dissociation constants of folic acid, Dihydrofolic acid, and methotrexate
J Biol Chem 1977 Jun 10;252(11):3724-8.PMID:16913doi
The acidic dissociation constants in the range HO--1.5 to pH 7 of folic acid, Dihydrofolic acid, methopterin (N(10)methylfolic acid), and methotrexate have been measured by potentiometric and spectrophotometric titrations. Assignment of these dissociations was made by comparison to model compounds, by proton magnetic resonance measurements, and by examination of associated ultraviolet absorbance changes. For folic acid, the dissociation constants are as follows: N(1), pK' 2.35; N(10), pK' 0.20; N(5), pK' greater than -1.5. For Dihydrofolic acid: N(5), pK' 3.84; N(1), pK' 1.38; N(10), pK' 0.28. For methotrexate: N(1), pK' 5.71; gamma-carboxyl, pK' 4.70; alpha-carboxyl, pK' 3.36; N(10), pK' 0.50; N(5), boxyl, pK' 4.70; alpha-carboxyl, pK' 3.36; N(10), pK' 0.50; N(5) pK' greater than -1.5. For methopterin: acidic ionization of amide, pK' 7.68; gamma-carboxyl, pK' 4.62; N(1), pK' 2.40; N(10), pK; 0.36; N(5), pK' greater than -1.5. The pK' values were determined directly for the four compounds at 25 degrees near 0.1 ionic strength, or in 0.1 to 4 M HCl for pK ln 0.1 M NaCl.
A computational chemistry-driven hypothesis on the mode of action of hipposudoric acid and related analogs
Future Med Chem 2022 Aug;14(15):1115-1131.PMID:35796603DOI:10.4155/fmc-2022-0067.
Aim: To elucidate the mode of action of the hipposudoric acid derivatives and identify hit compounds for synthesis. Materials & methods: Structural fragments of known bioactive fluorenes were introduced onto the hipposudoric acid scaffold to yield novel derivatives. The binding motifs of the novel compounds were compared to the pharmacophore of DHFR co-crystallized with methotrexate (MTX). Results: Several of the novel compounds showed binding affinities that exceeded the affinity of the docked endogenous ligand (Dihydrofolic acid). Conclusion: This study indicates that compounds 3r12, 3r9, 1s9 and 3r10 are promising candidates for synthesis and pharmacological evaluation.
Dissociation constants for Dihydrofolic acid and dihydrobiopterin and implications for mechanistic models for dihydrofolate reductase
Biochemistry 1990 May 15;29(19):4554-60.PMID:2372539DOI:10.1021/bi00471a008.
The dissociation constants (pKa) for the pteridine ring system of dihydrofolate (H2folate) have been redetermined, and those for dihydrobiopterin (H2biopterin) have been determined. Determination of the pKa for N5 of H2folate is complicated by the low solubility and instability of H2folate at pH 2-4, and other complicating factors. The initial rate of absorbance change due to degradation is a maximum at pH 2.5, and the products depend on the oxygen concentration: under aerobic conditions, (p-aminobenzoyl)glutamic acid and 7,8-dihydropterin-6-carboxaldehyde are major products. H2Biopterin is much more soluble and more stable at low pH. For protonation of N5, the pKa is 2.56 +/- 0.01 for H2biopterin and 2.59 +/- 0.03 for H2folic acid. Spectrophotometric determination of the pKa for the N3-O4 amide group of H2folate is subject to serious errors when a wavelength between 220 and 235 nm is used. These errors arise from the pH-dependent absorbance of mercaptoethanol often present in the preparation. The amide group has a pKa of 10.41 +/- 0.04 in H2biopterin and 10.85 +/- 0.04 in H2folate. The redetermined value for the pKa of N5 of H2folate has implications for mechanistic models for dihydrofolate reductase, and revised kinetic constants have been calculated for one model.
The nucleotide sequence of the cDNA coding for the human Dihydrofolic acid reductase
Gene 1983 Jan-Feb;21(1-2):59-63.PMID:6687716DOI:10.1016/0378-1119(83)90147-6.
The nucleotide sequence of the human Dihydrofolic acid reductase (DHFR) reading frame has been derived from the analysis of human DHFR cDNA. This sequence and the corresponding amino acid sequence have been compared with those available for the enzyme and its coding segment from other organisms. There is an 89% nucleotide sequence homology between the human DHFR reading frame and the mouse coding sequence. Furthermore, amino acid-sequence homologies of 74%, 81% and 89% has been found between human DHFR and chicken, bovine and mouse DHFR, respectively.