L-AP4
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MedKoo CAT#: 596856

CAS#: 23052-81-5

Description: L-AP4 is the phosphonic acid analog of L-glutamic acid. A selective group III metabotropic glutamate receptor agonist. Also a potent, pathway-specific synaptic depressant.

Chemical Structure

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L-AP4
CAS# 23052-81-5
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 596856
Name: L-AP4
CAS#: 23052-81-5
Chemical Formula: C4H10NO5P
Exact Mass: 183.03
Molecular Weight: 183.100
Elemental Analysis: C, 26.24; H, 5.51; N, 7.65; O, 43.69; P, 16.92

Price and Availability

Size Price Availability Quantity
5mg USD 295 2 Weeks
10mg USD 500 2 Weeks
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Synonym: L-AP4; L AP4; LAP4;

IUPAC/Chemical Name: 2-amino-4-phosphonobutanoic acid

InChi Key: DDOQBQRIEWHWBT-UHFFFAOYSA-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)

SMILES Code: O=C(O)C(N)CCP(O)(O)=O

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info:

Product Data:
Product Data
Instruction:
View handling instruction
Biological target: L-AP4 (L-APB) is a potent and specific agonist for the group III mGluRs, with EC50s of 0.13, 0.29, 1.0, 249 μM for mGlu4, mGlu8, mGlu6 and mGlu7 receptors, respectively.
In vitro activity: Application of 100 microM L-2-amino-4-phosphonobutyrate (L-AP4), a class III mGluR-specific agonist, induced a rise in [Ca2+]i in hmGlu(R4)1-519/1b but not in hmGluR1b expressing cells. Reference: Neuroreport. 1995 Dec 29;7(1):117-20. https://pubmed.ncbi.nlm.nih.gov/8742431/
In vivo activity: An intrathecal (5-30 microg) L-AP4 dose-dependently attenuated allodynia in nerve-injured rats but had no antinociceptive effect in normal rats. Topical spinal application of 5 to 50 microM L-AP4 also significantly inhibited the evoked responses of ascending dorsal horn neurons in nerve-ligated but not normal rats. Reference: J Pharmacol Exp Ther. 2005 Jan;312(1):120-6. https://pubmed.ncbi.nlm.nih.gov/15375175/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
PBS (pH 7.2) 2.0 10.92
Water 25.5 139.05

Preparing Stock Solutions

The following data is based on the product molecular weight 183.10 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Tones MA, Bendali N, Flor PJ, Knöpfel T, Kuhn R. The agonist selectivity of a class III metabotropic glutamate receptor, human mGluR4a, is determined by the N-terminal extracellular domain. Neuroreport. 1995 Dec 29;7(1):117-20. PMID: 8742431. 2. Takemoto Y. L-Cysteine and L-AP4 microinjections in the rat caudal ventrolateral medulla decrease arterial blood pressure. Auton Neurosci. 2014 Dec;186:45-53. doi: 10.1016/j.autneu.2014.09.018. Epub 2014 Oct 2. PMID: 25450419. 3. Chen SR, Pan HL. Distinct roles of group III metabotropic glutamate receptors in control of nociception and dorsal horn neurons in normal and nerve-injured Rats. J Pharmacol Exp Ther. 2005 Jan;312(1):120-6. doi: 10.1124/jpet.104.073817. Epub 2004 Sep 16. PMID: 15375175.
In vitro protocol: 1. Tones MA, Bendali N, Flor PJ, Knöpfel T, Kuhn R. The agonist selectivity of a class III metabotropic glutamate receptor, human mGluR4a, is determined by the N-terminal extracellular domain. Neuroreport. 1995 Dec 29;7(1):117-20. PMID: 8742431.
In vivo protocol: 1. Takemoto Y. L-Cysteine and L-AP4 microinjections in the rat caudal ventrolateral medulla decrease arterial blood pressure. Auton Neurosci. 2014 Dec;186:45-53. doi: 10.1016/j.autneu.2014.09.018. Epub 2014 Oct 2. PMID: 25450419. 2. Chen SR, Pan HL. Distinct roles of group III metabotropic glutamate receptors in control of nociception and dorsal horn neurons in normal and nerve-injured Rats. J Pharmacol Exp Ther. 2005 Jan;312(1):120-6. doi: 10.1124/jpet.104.073817. Epub 2004 Sep 16. PMID: 15375175.

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1: Schkeryantz JM, Chen Q, Ho JD, Atwell S, Zhang A, Vargas MC, Wang J, Monn JA, Hao J. Determination of L-AP4-bound human mGlu8 receptor amino terminal domain structure and the molecular basis for L-AP4's group III mGlu receptor functional potency and selectivity. Bioorg Med Chem Lett. 2018 Feb 15;28(4):612-617. doi: 10.1016/j.bmcl.2018.01.037. Epub 2018 Jan 31. PubMed PMID: 29402739.

2: Selvam C, Lemasson IA, Brabet I, Oueslati N, Karaman B, Cabaye A, Tora AS, Commare B, Courtiol T, Cesarini S, McCort-Tranchepain I, Rigault D, Mony L, Bessiron T, McLean H, Leroux FR, Colobert F, Daniel H, Goupil-Lamy A, Bertrand HO, Goudet C, Pin JP, Acher FC. Increased Potency and Selectivity for Group III Metabotropic Glutamate Receptor Agonists Binding at Dual sites. J Med Chem. 2018 Mar 8;61(5):1969-1989. doi: 10.1021/acs.jmedchem.7b01438. Epub 2018 Feb 14. PubMed PMID: 29397723.

3: Martín R, Ferrero JJ, Collado-Alsina A, Aguado C, Luján R, Torres M, Sánchez-Prieto J. Bidirectional modulation of glutamatergic synaptic transmission by metabotropic glutamate type 7 receptors at Schaffer collateral-CA1 hippocampal synapses. J Physiol. 2018 Mar 1;596(5):921-940. doi: 10.1113/JP275371. Epub 2018 Jan 25. PubMed PMID: 29280494; PubMed Central PMCID: PMC5830420.

4: Dammann F, Kirschstein T, Guli X, Müller S, Porath K, Rohde M, Tokay T, Köhling R. Bidirectional shift of group III metabotropic glutamate receptor-mediated synaptic depression in the epileptic hippocampus. Epilepsy Res. 2018 Jan;139:157-163. doi: 10.1016/j.eplepsyres.2017.12.002. Epub 2017 Dec 8. PubMed PMID: 29224956.

5: Chardonnet S, Bessiron T, Ramos CI, Dammak R, Richard MA, Boursier C, Cadilhac C, Coquelle FM, Bossi S, Ango F, Le Maréchal P, Decottignies P, Berrier C, McLean H, Daniel H. Native metabotropic glutamate receptor 4 depresses synaptic transmission through an unusual Gα(q) transduction pathway. Neuropharmacology. 2017 Jul 15;121:247-260. doi: 10.1016/j.neuropharm.2017.04.036. Epub 2017 Apr 26. PubMed PMID: 28456688.

6: Van Hook MJ, Babai N, Zurawski Z, Yim YY, Hamm HE, Thoreson WB. A Presynaptic Group III mGluR Recruits Gβγ/SNARE Interactions to Inhibit Synaptic Transmission by Cone Photoreceptors in the Vertebrate Retina. J Neurosci. 2017 Apr 26;37(17):4618-4634. doi: 10.1523/JNEUROSCI.2948-16.2017. Epub 2017 Mar 31. PubMed PMID: 28363980; PubMed Central PMCID: PMC5413191.

7: Sabharwal J, Seilheimer RL, Cowan CS, Wu SM. The ON Crossover Circuitry Shapes Spatiotemporal Profile in the Center and Surround of Mouse OFF Retinal Ganglion Cells. Front Neural Circuits. 2016 Dec 22;10:106. doi: 10.3389/fncir.2016.00106. eCollection 2016. PubMed PMID: 28066192; PubMed Central PMCID: PMC5177742.

8: Iacovelli L, Di Menna L, Peterlik D, Stangl C, Orlando R, Molinaro G, De Blasi A, Bruno V, Battaglia G, Flor PJ, Uschold-Schmidt N, Nicoletti F. Type-7 metabotropic glutamate receptors negatively regulate α(1)-adrenergic receptor signalling. Neuropharmacology. 2017 Feb;113(Pt A):343-353. doi: 10.1016/j.neuropharm.2016.10.018. Epub 2016 Oct 18. PubMed PMID: 27769854.

9: Fujii M, Sunagawa GA, Kondo M, Takahashi M, Mandai M. Evaluation of micro Electroretinograms Recorded with Multiple Electrode Array to Assess Focal Retinal Function. Sci Rep. 2016 Aug 2;6:30719. doi: 10.1038/srep30719. PubMed PMID: 27480484; PubMed Central PMCID: PMC4969741.

10: Chen X, Liu Y, Zhang Z, Miao X, Tian Y, Yao L, Liu J, Lu H, Liu Y. Hypoxia stimulates the proliferation of rat neural stem cells by regulating the expression of metabotropic glutamate receptors: an in vitro study. Cell Mol Biol (Noisy-le-grand). 2016 Mar 31;62(3):105-14. PubMed PMID: 27064882.

11: Pal Choudhuri S, Delay RJ, Delay ER. Metabotropic glutamate receptors are involved in the detection of IMP and L-amino acids by mouse taste sensory cells. Neuroscience. 2016 Mar 1;316:94-108. doi: 10.1016/j.neuroscience.2015.12.008. Epub 2015 Dec 14. PubMed PMID: 26701297.

12: Montesano G, Belfiore M, Ripamonti M, Arena A, Lamanna J, Ferro M, Zimarino V, Ambrosi A, Malgaroli A. Effects of the Concomitant Activation of ON and OFF Retinal Ganglion Cells on the Visual Thalamus: Evidence for an Enhanced Recruitment of GABAergic Cells. Front Neural Circuits. 2015 Nov 24;9:77. doi: 10.3389/fncir.2015.00077. eCollection 2015. PubMed PMID: 26635537; PubMed Central PMCID: PMC4656840.

13: Choi JH, Park JY, Park SP, Lee H, Han S, Park KH, Suh YH. Regulation of mGluR7 trafficking by SUMOylation in neurons. Neuropharmacology. 2016 Mar;102:229-35. doi: 10.1016/j.neuropharm.2015.11.021. Epub 2015 Nov 26. PubMed PMID: 26631532.

14: Ferrero JJ, Ramírez-Franco J, Martín R, Bartolomé-Martín D, Torres M, Sánchez-Prieto J. Cross-talk between metabotropic glutamate receptor 7 and beta adrenergic receptor signaling at cerebrocortical nerve terminals. Neuropharmacology. 2016 Feb;101:412-25. doi: 10.1016/j.neuropharm.2015.07.025. Epub 2015 Jul 23. PubMed PMID: 26211974.

15: Spaziano G, Luongo L, Guida F, Petrosino S, Matteis M, Palazzo E, Sullo N, de Novellis V, Di Marzo V, Rossi F, Maione S, D'Agostino B. Exposure to Allergen Causes Changes in NTS Neural Activities after Intratracheal Capsaicin Application, in Endocannabinoid Levels and in the Glia Morphology of NTS. Biomed Res Int. 2015;2015:980983. doi: 10.1155/2015/980983. Epub 2015 Mar 19. PubMed PMID: 25866824; PubMed Central PMCID: PMC4383154.

16: Spampinato SF, Merlo S, Chisari M, Nicoletti F, Sortino MA. Glial metabotropic glutamate receptor-4 increases maturation and survival of oligodendrocytes. Front Cell Neurosci. 2015 Jan 14;8:462. doi: 10.3389/fncel.2014.00462. eCollection 2014. PubMed PMID: 25642169; PubMed Central PMCID: PMC4294134.

17: Yasumatsu K, Manabe T, Yoshida R, Iwatsuki K, Uneyama H, Takahashi I, Ninomiya Y. Involvement of multiple taste receptors in umami taste: analysis of gustatory nerve responses in metabotropic glutamate receptor 4 knockout mice. J Physiol. 2015 Feb 15;593(4):1021-34. doi: 10.1113/jphysiol.2014.284703. Epub 2015 Jan 22. PubMed PMID: 25529865; PubMed Central PMCID: PMC4398535.

18: Takemoto Y. L-Cysteine and L-AP4 microinjections in the rat caudal ventrolateral medulla decrease arterial blood pressure. Auton Neurosci. 2014 Dec;186:45-53. doi: 10.1016/j.autneu.2014.09.018. Epub 2014 Oct 2. PubMed PMID: 25450419.

19: Rovira X, Malhaire F, Scholler P, Rodrigo J, Gonzalez-Bulnes P, Llebaria A, Pin JP, Giraldo J, Goudet C. Overlapping binding sites drive allosteric agonism and positive cooperativity in type 4 metabotropic glutamate receptors. FASEB J. 2015 Jan;29(1):116-30. doi: 10.1096/fj.14-257287. Epub 2014 Oct 23. PubMed PMID: 25342125.

20: Jalan-Sakrikar N, Field JR, Klar R, Mattmann ME, Gregory KJ, Zamorano R, Engers DW, Bollinger SR, Weaver CD, Days EL, Lewis LM, Utley TJ, Hurtado M, Rigault D, Acher F, Walker AG, Melancon BJ, Wood MR, Lindsley CW, Conn PJ, Xiang Z, Hopkins CR, Niswender CM. Identification of positive allosteric modulators VU0155094 (ML397) and VU0422288 (ML396) reveals new insights into the biology of metabotropic glutamate receptor 7. ACS Chem Neurosci. 2014 Dec 17;5(12):1221-37. doi: 10.1021/cn500153z. Epub 2014 Oct 9. PubMed PMID: 25225882; PubMed Central PMCID: PMC4306484.