 Chemical Structure.png)
Physicochemical Properties
| Molecular Formula | C4H10NO5P |
| Molecular Weight | 183.10 |
| Exact Mass | 183.03 |
| Elemental Analysis | C, 26.24; H, 5.51; N, 7.65; O, 43.69; P, 16.92 |
| CAS # | 78739-01-2 |
| Related CAS # | L-AP4;23052-81-5;L-AP4 monohydrate;2247534-79-6 |
| PubChem CID | 1550579 |
| Appearance | Typically exists as solid at room temperature |
| Density | 1.628g/cm3 |
| Boiling Point | 491.7ºC at 760 mmHg |
| Melting Point | 212-213ºC |
| Flash Point | 251.2ºC |
| Index of Refraction | 1.545 |
| LogP | -5.5 |
| Hydrogen Bond Donor Count | 4 |
| Hydrogen Bond Acceptor Count | 6 |
| Rotatable Bond Count | 4 |
| Heavy Atom Count | 11 |
| Complexity | 187 |
| Defined Atom Stereocenter Count | 1 |
| SMILES | C(CP(=O)(O)O)[C@H](C(=O)O)N |
| InChi Key | DDOQBQRIEWHWBT-GSVOUGTGSA-N |
| InChi Code | InChI=1S/C4H10NO5P/c5-3(4(6)7)1-2-11(8,9)10/h3H,1-2,5H2,(H,6,7)(H2,8,9,10)/t3-/m1/s1 |
| Chemical Name | (2R)-2-amino-4-phosphonobutanoic acid |
| Synonyms | D-AP4; 78739-01-2; (2R)-2-amino-4-phosphonobutanoic acid; (R)-2-Amino-4-phosphonobutanoic acid; Butanoic acid, 2-amino-4-phosphono-, (2R)-; |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | mGluR |
| ln Vitro | This study describes the inhibition of 57Co2+ influx through Ca2+-permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, consequent to the application of L-2-amino-4-phosphonobutanoic acid (L-AP4), D-AP4 and L-serine-O-phosphate (L-SOP) in cultured cerebellar granule cells. The forskolin-stimulated accumulation of cyclic AMP was inhibited by (2S,1'S,2'S)-2-(carboxycyclopropyl)glycine (L-CCG-1) with an IC50 = 491 +/- 135 nM and by L-AP4 in a biphasic manner (IC50(1) = 232 +/- 61 nM and IC50(2) = >300 microM), confirming the presence of group II and group III mGlu receptors, respectively. 57Co2+ influx was stimulated by kainate (EC50 = 42.2 +/- 11.3 microM) and, in the presence of 30 microM cyclothiazide, by (S)-5-fluorowillardiine (EC50 = 0.7 +/- 0.1 microM) and (S)-AMPA (EC50 = 2.8 +/- 0.5 microM). The effects of the latter were abolished by 10 microM 6-nitro-7-sulphamoylbenzo[f]quinoxaline-2,3-dione (NBQX). L-AP4 (IC50 = >300 microM), D-AP4 (IC50 = >100 microM) and L-SOP (IC50 = 199 +/- 6 microM) inhibited 6 microM (S)-AMPA-stimulated 57Co2+ influx, whereas L-CCG-1 (up to 10 microM), 300 microM (RS)-3,5-dihydroxyphenylglycine, 300 microM (+/-)-baclofen and 1 mM carbachol were ineffective. Pre-incubation with either pertussis toxin (250 ng/ml, 48 hr), 1 mM dibutyryl cyclic AMP, or the potent group III mGlu receptor antagonist (RS)-alpha-cyclopropyl-4-phosphonophenylglycine ((RS)-CPPG), tested at 400 microM, failed to alter the inhibition of AMPA receptor activity by 300 microM L-SOP. Unlike 10 microM NBQX, neither L-AP4, D-AP4 or L-SOP (tested at 1 mM) inhibited the binding of 10 nM (S)-[3H]5-fluorowillardiine (a selective AMPA receptor ligand) to granule cell membranes. Therefore, in these neurones, high concentrations (>100 microM) of L-AP4, L-SOP and D-AP4 inhibit Ca2+-permeable AMPA receptors by a mechanism distinct from known mGlu receptor action and at a site independent from that for AMPA receptor agonists [3]. |
| ln Vivo |
1 The depressant actions on evoked electrical activity and the excitant amino acid antagonist properties of a range of omega-phosphonic alpha-carboxylic amino acids have been investigated in the isolated spinal cord preparations of the frog or immature rat. 2 When tested on dorsal root-evoked ventral root potentials, members of the homologous series from 2- amino-5-phosphonovaleric acid to 2-amino-8-phosphonooctanoic acid showed depressant actions which correlated with the ability of the substances to antagonize selectivity motoneuronal depolarizations induced by N-methyl-D-aspartate. 3 2-Amino-5-phosphonovalerate was the most potent substance of the series giving an apparent KD of 1.4 microM for the antagonism of responses to N-methyl-D-aspartate. 4 A comparison of the (+)- and (-)-forms of 2-amino-5-phosphonovalerate indicated that the N-methyl-D-aspartate antagonist activity and the neuronal depressant action of this substance were both due mainly to the (-)-isomer. 5 The (-)- and (+)-forms of 2-amino-4-phosphonobutyrate had different actions. The (-)-forms of this substance had a relatively weak and non-selective antagonist action on depolarizations induced by N-methyl-D-aspartate, quisqualate and kainate and a similarly weak depressant effect when tested on evoked electrical activity. The (+)-form was more potent than he (-)-form in depressing electrically evoked activity but did not antagonize responses to amino acid excitants. At concentrations higher than those required to depress electrically evoked activity, the (+)-form produced depolarization. This action was blocked by 2-amino-5-phosphonovalerate. [1] Brief exposure of rat hippocampal slices to quisqualic acid (QUIS) sensitizes neurons to depolarization by the alpha-amino-omega-phosphonate excitatory amino acid (EAA) analogues AP4, AP5 and AP6. These phosphonates interact with a novel QUIS-sensitized site. Whereas L-AP4 and D-AP5 cross-react with other EAA receptors, DL-AP6 has been shown to be relatively selective for the QUIS-sensitized site. This specificity of DL-AP6, in conjunction with the apparent preference of this site for L-isomers, suggested that the hitherto unavailable L-isomer of AP6 would be a potent and specific agonist. We report the resolution of the D- and L-enantiomers of AP6 by fractional crystallization of the L-lysine salt of DL-AP6. We also report the pharmacological responses of kainate/AMPA, NMDA, lateral perforant path L-AP4 receptors and the CA1 QUIS-sensitized site to D- and L-AP6, and compare these responses to the D- and L-isomers of AP3, AP4, AP5 and AP7. The D-isomers of AP4, AP5 and AP6 were 5-, 3- and 14-fold less potent for the QUIS-sensitized site than their respective L-isomers. While L-AP4 and L-AP5 cross-reacted with NMDA and L-AP4 receptors, L-AP6 was found to be highly potent and specific for the QUIS-sensitized site (IC50 = 40 microM). Its IC50 values for kainate/AMPA, NMDA and L-AP4 receptors were > 10, 3 and 0.8 mM, respectively. As with AP4 and AP5, sensitization to L-AP6 was reversed by L-alpha-aminoadipate.[2] |
| References |
[1]. The effects of a series of omega-phosphonic alpha-carboxylic amino acids on electrically evoked and excitant amino acid-induced responses in isolated spinal cord preparations. Br J Pharmacol. 1982;75(1):65-75. [2]. Utilization of the resolved L-isomer of 2-amino-6-phosphonohexanoic acid (L-AP6) as a selective agonist for a quisqualate-sensitized site in hippocampal CA1 pyramidal neurons. Brain Res. 1994;649(1-2):203-207. [3]. Inhibition of AMPA receptor-stimulated 57Co2+ influx by D- and L-2-amino-4-phosphonobutanoic acid (D- and L-AP4) and L-serine-O-phosphate (L-SOP) in cultured cerebellar granule cells. Neuropharmacology. 1997;36(3):335-343. |
Solubility Data
| Solubility (In Vitro) | May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples |
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 5.4615 mL | 27.3075 mL | 54.6150 mL | |
| 5 mM | 1.0923 mL | 5.4615 mL | 10.9230 mL | |
| 10 mM | 0.5461 mL | 2.7307 mL | 5.4615 mL |