Identification

Name
Mimosine
Accession Number
DB01055  (APRD00647)
Type
Small Molecule
Groups
Approved
Description

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

Structure
Thumb
Synonyms
  • (S)-2-Amino-3-(3-hydroxy-4-oxo-4H-pyridin-1-yl)propanoate
  • L-Mimosine
  • Leucaenine
  • Leucaenol
  • Leucenine
  • Leucenol
  • Mimosin
External IDs
NSC-69188
Categories
UNII
Z46B1LUI5N
CAS number
500-44-7
Weight
Average: 198.176
Monoisotopic: 198.064056818
Chemical Formula
C8H10N2O4
InChI Key
WZNJWVWKTVETCG-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[[email protected]@H](CN1C=CC(=O)C(O)=C1)C(O)=O

Pharmacology

Indication
Not Available
Structured Indications
Not Available
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.

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.

TargetActionsOrganism
ASerine hydroxymethyltransferase, cytosolic
inhibitor
Human
AC-C motif chemokine 2
inhibitor
Human
UTyrosinase
inhibitor
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding

>99.5%

Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB15188
KEGG Compound
C04771
PubChem Compound
440473
PubChem Substance
46505895
ChemSpider
389405
BindingDB
50198715
ChEBI
29063
ChEMBL
CHEMBL245416
Therapeutic Targets Database
DNC000947
PharmGKB
PA164752445
HET
MMS
Wikipedia
Mimosine
PDB Entries
5m8n / 5m8r
MSDS
Download (61 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)228 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 FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
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 inhibitorNon-inhibitor0.9388
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.953
CYP450 3A4 inhibitorNon-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
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This 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.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
L-alpha-amino acids
Alternative Parents
Hydroxypyridines / Dihydropyridines / Vinylogous amides / Heteroaromatic compounds / Cyclic ketones / Amino acids / Monocarboxylic acids and derivatives / Carboxylic acids / Azacyclic compounds / Organopnictogen compounds
show 3 more
Substituents
L-alpha-amino acid / Dihydropyridine / Hydroxypyridine / Hydropyridine / Pyridine / Heteroaromatic compound / Vinylogous amide / Amino acid / Cyclic ketone / Carboxylic acid
show 15 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
non-proteinogenic L-alpha-amino acid (CHEBI:29063)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Serine binding
Specific Function
Interconversion of serine and glycine.
Gene Name
SHMT1
Uniprot ID
P34896
Uniprot Name
Serine hydroxymethyltransferase, cytosolic
Molecular Weight
53082.18 Da
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:10766749]
  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:11936838]
  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:15531579]
  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:8576220]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Not Available
Specific Function
Not Available
Gene Name
CCL2
Uniprot ID
P13500
Uniprot Name
C-C motif chemokine 2
Molecular Weight
11024.87 Da
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:11936838]
  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:15698514]
Details
3. Tyrosinase
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Protein homodimerization activity
Specific Function
This is a copper-containing oxidase that functions in the formation of pigments such as melanins and other polyphenolic compounds. Catalyzes the rate-limiting conversions of tyrosine to DOPA, DOPA ...
Gene Name
TYR
Uniprot ID
P14679
Uniprot Name
Tyrosinase
Molecular Weight
60392.69 Da
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:15577244]
  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:16750372]
  3. Sugumaran M: Tyrosinase catalyzes an unusual oxidative decarboxylation of 3,4-dihydroxymandelate. Biochemistry. 1986 Aug 12;25(16):4489-92. [PubMed:3094574]
  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:6234942]

Drug created on June 13, 2005 07:24 / Updated on November 07, 2017 01:46