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Identification
NameMimosine
Accession NumberDB01055  (APRD00647)
TypeSmall Molecule
GroupsApproved
Description

3-Hydroxy-4-oxo-1(4H)-pyridinealanine. An antineoplastic alanine-substituted pyridine derivative isolated from Leucena glauca. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
(S)-2-Amino-3-(3-hydroxy-4-oxo-4H-pyridin-1-yl)propanoateNot AvailableNot Available
L-MimosineNot AvailableNot Available
LeucaenineNot AvailableNot Available
LeucaenolNot AvailableNot Available
LeucenineNot AvailableNot Available
LeucenolNot AvailableNot Available
MimosinNot AvailableNot Available
Prescription ProductsNot Available
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
CategoriesNot Available
CAS number500-44-7
WeightAverage: 198.176
Monoisotopic: 198.064056818
Chemical FormulaC8H10N2O4
InChI KeyWZNJWVWKTVETCG-YFKPBYRVSA-N
InChI
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
IUPAC Name
(2S)-2-amino-3-(3-hydroxy-4-oxo-1,4-dihydropyridin-1-yl)propanoic acid
SMILES
N[C@@H](CN1C=CC(=O)C(O)=C1)C(O)=O
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as l-alpha-amino acids. These are alpha amino acids which have the L-configuration of the alpha-carbon atom.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentL-alpha-amino acids
Alternative Parents
Substituents
  • L-alpha-amino acid
  • Hydroxypyridine
  • Dihydropyridine
  • Pyridine
  • Hydropyridine
  • Heteroaromatic compound
  • Vinylogous amide
  • Cyclic ketone
  • Azacycle
  • Organoheterocyclic compound
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Hydrocarbon derivative
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Primary aliphatic amine
  • Carbonyl group
  • Amine
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Pharmacology
IndicationNot Available
PharmacodynamicsMimosine 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.
Mechanism of actionMimosine 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.
AbsorptionNot Available
Volume of distributionNot Available
Protein binding>99.5%
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.6591
Blood Brain Barrier-0.9388
Caco-2 permeable-0.7696
P-glycoprotein substrateSubstrate0.653
P-glycoprotein inhibitor INon-inhibitor0.979
P-glycoprotein inhibitor IINon-inhibitor0.9717
Renal organic cation transporterNon-inhibitor0.8735
CYP450 2C9 substrateNon-substrate0.8796
CYP450 2D6 substrateNon-substrate0.8236
CYP450 3A4 substrateNon-substrate0.7208
CYP450 1A2 substrateNon-inhibitor0.9115
CYP450 2C9 substrateNon-inhibitor0.9388
CYP450 2D6 substrateNon-inhibitor0.9231
CYP450 2C19 substrateNon-inhibitor0.953
CYP450 3A4 substrateNon-inhibitor0.9881
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9919
Ames testNon AMES toxic0.6831
CarcinogenicityNon-carcinogens0.9491
BiodegradationNot ready biodegradable0.818
Rat acute toxicity2.1155 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9793
hERG inhibition (predictor II)Non-inhibitor0.8617
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point228 dec °CPhysProp
logP-2.5Not Available
Predicted Properties
PropertyValueSource
Water Solubility13.1 mg/mLALOGPS
logP-2.4ALOGPS
logP-3ChemAxon
logS-1.2ALOGPS
pKa (Strongest Acidic)1.94ChemAxon
pKa (Strongest Basic)8.88ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area103.86 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity48.66 m3·mol-1ChemAxon
Polarizability18.2 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
General ReferenceNot Available
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB Entries
FDA labelNot Available
MSDSDownload (61 KB)
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

1. Serine hydroxymethyltransferase, cytosolic

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Serine hydroxymethyltransferase, cytosolic P34896 Details

References:

  1. Oppenheim EW, Nasrallah IM, Mastri MG, Stover PJ: Mimosine is a cell-specific antagonist of folate metabolism. J Biol Chem. 2000 Jun 23;275(25):19268-74. Pubmed
  2. Conti P, Frydas S, Reale M, Barbacane RC, Di Gioacchino M, Felaco M, Trakatellis A: Inhibition of MCP-1 and MIP-2 transcription and translation by mimosine in muscle tissue infected with the parasite Trichinella spiralis. Mol Cell Biochem. 2002 Jan;229(1-2):129-37. Pubmed
  3. Perry C, Sastry R, Nasrallah IM, Stover PJ: Mimosine attenuates serine hydroxymethyltransferase transcription by chelating zinc. Implications for inhibition of DNA replication. J Biol Chem. 2005 Jan 7;280(1):396-400. Epub 2004 Nov 4. Pubmed
  4. Lin HB, Falchetto R, Mosca PJ, Shabanowitz J, Hunt DF, Hamlin JL: Mimosine targets serine hydroxymethyltransferase. J Biol Chem. 1996 Feb 2;271(5):2548-56. Pubmed

2. C-C motif chemokine 2

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
C-C motif chemokine 2 P13500 Details

References:

  1. Conti P, Frydas S, Reale M, Barbacane RC, Di Gioacchino M, Felaco M, Trakatellis A: Inhibition of MCP-1 and MIP-2 transcription and translation by mimosine in muscle tissue infected with the parasite Trichinella spiralis. Mol Cell Biochem. 2002 Jan;229(1-2):129-37. Pubmed
  2. Frydas S, Papaioannou N, Papazahariadou M, Hatzistilianou M, Karagouni E, Trakatelli M, Brellou G, Petrarca C, Castellani ML, Conti P, Riccioni G, Patruno A, Grilli A: Inhibition of MCP-1 and MIP-2 chemokines in murine trichinellosis: effect of the anti-inflammatory compound L-mimosine. Int J Immunopathol Pharmacol. 2005 Jan-Mar;18(1):85-94. Pubmed

3. Tyrosinase

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Tyrosinase P14679 Details

References:

  1. Ahmad VU, Ullah F, Hussain J, Farooq U, Zubair M, Khan MT, Choudhary MI: Tyrosinase inhibitors from Rhododendron collettianum and their structure-activity relationship (SAR) studies. Chem Pharm Bull (Tokyo). 2004 Dec;52(12):1458-61. Pubmed
  2. Khan KM, Mughal UR, Khan MT, Zia-Ullah, Perveen S, Choudhary MI: Oxazolones: new tyrosinase inhibitors; synthesis and their structure-activity relationships. Bioorg Med Chem. 2006 Sep 1;14(17):6027-33. Epub 2006 Jun 5. Pubmed
  3. Sugumaran M: Tyrosinase catalyzes an unusual oxidative decarboxylation of 3,4-dihydroxymandelate. Biochemistry. 1986 Aug 12;25(16):4489-92. Pubmed
  4. Woolery GL, Powers L, Winkler M, Solomon EI, Lerch K, Spiro TG: Extended X-ray absorption fine structure study of the coupled binuclear copper active site of tyrosinase from Neurospora crassa. Biochim Biophys Acta. 1984 Jul 31;788(2):155-61. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:13