In cultured vascular cells, l-mimosine acted as a prolyl 4-hydroxylase inhibitor. L-mimosine inhibited prolyl hydroxylase activity in rat and human smooth muscle cells (SMC) dose-dependently, and at concentrations of 400–500 M reduced hydroxyprolyl generation by 80–90%. At that concentration, [3H]proline incorporation decreased by about 20% in human SMC while increasing by about 20% in rat SMC. These findings showed that L-mimosine very specifically inhibited prolyl hydroxylation.

Physicochemical Properties

Molecular Formula	C8H10N2O4
Molecular Weight	198.18
Exact Mass	198.064
Elemental Analysis	C, 48.49; H, 5.09; N, 14.14; O, 32.29
CAS #	500-44-7
Related CAS #	500-44-7
PubChem CID	440473
Appearance	CRYSTALS FROM WATER TABLETS FROM WATER
Density	1.544g/cm3
Boiling Point	428.6ºC at 760mmHg
Melting Point	224-228 °C
Flash Point	213ºC
Index of Refraction	1.645
LogP	-3.5
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	3
Heavy Atom Count	14
Complexity	321
Defined Atom Stereocenter Count	1
SMILES	N[C@@H](CN1C=C(C(C=C1)=O)O)C(O)=O
InChi Key	WZNJWVWKTVETCG-YFKPBYRVSA-N
InChi Code	InChI=1S/C8H10N2O4/c9-5(8(13)14)3-10-2-1-6(11)7(12)4-10/h1-2,4-5,12H,3,9H2,(H,13,14)/t5-/m0/s1
Chemical Name	(2S)-2-amino-3-(3-hydroxy-4-oxopyridin-1-yl)propanoic acid
Synonyms	Leucenol; NSC 69188; NSC-69188; NSC69188; (L)-Mimosine
HS Tariff Code	2934.99.03.00
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product requires protection from light (avoid light exposure) during transportation and storage.
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

ln Vitro	L-Mimosine reduces cell proliferation by halting the cell cycle in PC-3 cells at the G1 phase and in LNCaP cells at the S phase. [1] L-mimosine, a prolyl hydroxylase (PHD) inhibitor, stimulates the synthesis of VEGF and boosts the proangiogenic potential of cells derived from dental pulp. [2]
ln Vivo	In Sprague-Dawley rats, L-mimosine (50 mg/kg i.p.) significantly increases the expression of HIF-1alpha in the kidneys and noticeably improves the natriuretic response to renal perfusion pressure. [3]
Enzyme Assay	In rats, it interfered with the reconstitution of the active human prolyl 4-hydroxylase with an IC50 value of 120 µM.
Cell Assay	Cell proliferation in response to L-mimosine is measured using a [3H]thymidine incorporation assay. In this test, RPMI-1640 medium with 10% FCS and various concentrations of L-mimosine (0-800 μM) are cultured in each well of a 12-well plate with 1 × 104 cells each. Each well of the 12-well plate receives 0.5 μCi/ml of [3H[3H]thymidine following the necessary incubation times (24 and 48 h). After that, the cells are incubated for 4 hours at 37°C in a humidified 5% CO2 environment. The following step involves washing the cells twice in cold phosphate-buffered saline (PBS) and once more in cold 5% trichloroacetic acid. By adding 0.5 ml of 0.5 N NaOH, cells are lysed. In a liquid scintillation analyzer, 400 μl of the solubilized cell solution are combined with 4 ml of scintillation cocktail, and the results are then tallied. Quadruplicates of each sample were examined.
Animal Protocol	Dissolved in Na2CO3 solution, pH 8.5; 50 mg/kg; i.p. injection Sprague-Dawley rats
ADME/Pharmacokinetics	Metabolism / Metabolites EXPERIMENTAL POISONING OF SHEEP HAS SHOWN THAT MIMOSINE IS LARGELY BROKEN DOWN IN THE RUMEN TO 3,4-DIHYDROXYPYRIDINE, AND EXCRETED AS SUCH. /MIMOSINE/
Toxicity/Toxicokinetics	Protein Binding >99.5%
References	[1]. Am J Physiol Cell Physiol. 2012 Feb 15;302(4):C676-85. [2]. J Endod . 2012 Nov;38(11):1498-503. [3]. Am J Physiol Renal Physiol. 2007 Jan;292(1):F207-16.
Additional Infomation	L-mimosine is an L-alpha-amino acid that is propionic acid substituted by an amino group at position 2 and a 3-hydroxy-4-oxopyridin-1(4H)-yl group at position 3 (the 2S-stereoisomer). It a non-protein plant amino acid isolated from Mimosa pudica. It has a role as an EC 1.14.18.1 (tyrosinase) inhibitor and a plant metabolite. It is a non-proteinogenic L-alpha-amino acid and a member of 4-pyridones. It is functionally related to a propionic acid. It is a conjugate acid of a L-mimosine(1-). It is a tautomer of a L-mimosine zwitterion. Mimosine is an antineoplastic alanine-substituted pyridine derivative isolated from Leucena glauca. L-mimosine has been reported in Arabidopsis thaliana, Euglena gracilis, and Caenorhabditis elegans with data available. 3-Hydroxy-4-oxo-1(4H)-pyridinealanine. An antineoplastic alanine-substituted pyridine derivative isolated from Leucena glauca. Mechanism of Action Mimosine causes inhibition of DNA replication, changes in the progression of the cells in the cell cycle, and apoptosis. Mimosine appears to introduce breaks into DNA. Mimosine is an iron/zinc chelator. Iron depletion induces DNA double-strand breaks in treated cells, and activates a DNA damage response that results in focal phosphorylation of histones. This leads to inhibition of DNA replication and/or DNA elongation. Some studies indicate that mimosine prevents the initiation of DNA replication, whereas other studies indicate that mimosine disrupts elongation of the replication fork by impairing deoxyribonucleotide synthesis by inhibiting the activity of the iron-dependent enzyme ribonucleotide reductase and the transcription of the cytoplasmic serine hydroxymethyltransferase gene (SHMT). Inhibition of serine hydroxymethyltransferase is moderated by a zinc responsive unit located in front of the SHMT gene. Pharmacodynamics Mimosine inhibits DNA synthesis at the level of elongation of nascent chains by altering deoxyribonucleotide metabolism. It arrests the cell cycle in the late G(1) phase.

Solubility Data

Solubility (In Vitro)	DMSO: <1 mg/mL Water: <1 mg/mL 10% NaHCO3 (aq): 38 mg/mL (191.74 mM)
Solubility (In Vivo)	Solubility in Formulation 1: 2 mg/mL (10.09 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	5.0459 mL	25.2296 mL	50.4592 mL
	5 mM	1.0092 mL	5.0459 mL	10.0918 mL
	10 mM	0.5046 mL	2.5230 mL	5.0459 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.