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Monoamine oxidase B

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Target id: 2490

Nomenclature: Monoamine oxidase B

Abbreviated Name: MAO-B

Family: Catecholamine turnover

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 520 Xp11.3 MAOB monoamine oxidase B
Mouse 1 520 X 11.88 cM Maob monoamine oxidase B
Rat 1 520 Xq11 Maob monoamine oxidase B
Database Links Click here for help
Alphafold P27338 (Hs), Q8BW75 (Mm), P19643 (Rn)
BRENDA 1.4.3.4
CATH/Gene3D 3.50.50.60
ChEMBL Target CHEMBL2039 (Hs), CHEMBL3050 (Mm), CHEMBL2993 (Rn)
DrugBank Target P27338 (Hs)
Ensembl Gene ENSG00000069535 (Hs), ENSMUSG00000040147 (Mm), ENSRNOG00000029778 (Rn)
Entrez Gene 4129 (Hs), 109731 (Mm), 25750 (Rn)
Human Protein Atlas ENSG00000069535 (Hs)
KEGG Enzyme 1.4.3.4
KEGG Gene hsa:4129 (Hs), mmu:109731 (Mm), rno:25750 (Rn)
OMIM 309860 (Hs)
Pharos P27338 (Hs)
RefSeq Nucleotide NM_000898 (Hs), NM_172778 (Mm), NM_013198 (Rn)
RefSeq Protein NP_000889 (Hs), NP_766366 (Mm), NP_037330 (Rn)
SynPHARM 81929 (in complex with safinamide)
81928 (in complex with safinamide)
UniProtKB P27338 (Hs), Q8BW75 (Mm), P19643 (Rn)
Wikipedia MAOB (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of human monoamine oxidase B in complex with the multi-target inhibitor ASS234
PDB Id:  4CRT
Ligand:  ASS234
Resolution:  1.8Å
Species:  Human
References:  5
Enzyme Reaction Click here for help
EC Number: 1.4.3.4
Cofactors Click here for help
Cofactor Species Comments Reference
flavin adenine dinucleotide Human

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Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
phenelzine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Irreversible inhibition 7.8 pKi 2
⤷ pKi 7.8 (Ki 1.5x10-8 M) [2]
lazabemide Small molecule or natural product Hs Inhibition 7.1 pKi 7,14
⤷ pKi 7.1 (Ki 8.4x10-8 M) [7,14]
safinamide Small molecule or natural product Approved drug Primary target of this compound Hs Inhibition 6.3 pKi 1
⤷ pKi 6.3 (Ki 4.5x10-7 M) [1]
moclobemide Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inhibition 6.0 pKi 8
⤷ pKi 6.0 (Ki 1.08x10-6 M) [8]
selegiline Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Inhibition 5.7 – 6.0 pKi 4,10
⤷ pKi 5.7 – 6.0 (Ki 1.96x10-6 – 9.7x10-7 M) [4,10]
bifemelane Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inhibition 4.3 pKi 11
⤷ pKi 4.3 (Ki 4.6x10-5 M) [11]
mofegiline Small molecule or natural product Immunopharmacology Ligand Rn Irreversible inhibition 8.4 pIC50 17
⤷ pIC50 8.4 (IC50 3.6x10-9 M) [17]
safinamide Small molecule or natural product Approved drug Primary target of this compound Hs Inhibition 8.1 pIC50 9
⤷ pIC50 8.1 (IC50 7.7x10-9 M) [9]
rasagiline Small molecule or natural product Approved drug Primary target of this compound Ligand has a PDB structure Hs Inhibition 7.8 pIC50 16
⤷ pIC50 7.8 (IC50 1.4x10-8 M) [16]
linezolid Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 5.7 – 8.3 pIC50 3,12
⤷ pIC50 8.3 (IC50 4.77x10-9 M) [3]
pIC50 5.7 (IC50 2.1x10-6 M) [12]
pargyline Small molecule or natural product Approved drug Rn Inhibition 5.7 pIC50 6
⤷ pIC50 5.7 (IC50 1.8x10-6 M) [6]
tranylcypromine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Inhibition 4.7 pIC50 15
⤷ pIC50 4.7 (IC50 1.9x10-5 M) [15]
View species-specific inhibitor tables
Inhibitor Comments
Differential inhibition of the A or B isozymes of MAO have different clinical outcomes. Inhibition of MAOA results in antidepressant activity [1], whereas inhibition of MAOB results in antiparkinsonian activity [13]. Important substrates for MAO activity in the CNS include dopamine, adrenaline, noradrenaline, serotonin (5-HT), and β-phenylethylamine.
Tranylcypromine is an irreversible MAO inhibitor with equal potency for the A and B isozymes [15].

References

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1. Binda C, Hubálek F, Li M, Herzig Y, Sterling J, Edmondson DE, Mattevi A. (2004) Crystal structures of monoamine oxidase B in complex with four inhibitors of the N-propargylaminoindan class. J Med Chem, 47 (7): 1767-74. [PMID:15027868]

2. Binda C, Wang J, Li M, Hubalek F, Mattevi A, Edmondson DE. (2008) Structural and mechanistic studies of arylalkylhydrazine inhibition of human monoamine oxidases A and B. Biochemistry, 47 (20): 5616-25. [PMID:18426226]

3. Boppana K, Dubey PK, Jagarlapudi SA, Vadivelan S, Rambabu G. (2009) Knowledge based identification of MAO-B selective inhibitors using pharmacophore and structure based virtual screening models. Eur J Med Chem, 44 (9): 3584-90. [PMID:19321235]

4. Di Santo R, Costi R, Roux A, Artico M, Befani O, Meninno T, Agostinelli E, Palmegiani P, Turini P, Cirilli R et al.. (2005) Design, synthesis, and biological activities of pyrrolylethanoneamine derivatives, a novel class of monoamine oxidases inhibitors. J Med Chem, 48 (13): 4220-3. [PMID:15974574]

5. Esteban G, Allan J, Samadi A, Mattevi A, Unzeta M, Marco-Contelles J, Binda C, Ramsay RR. (2014) Kinetic and structural analysis of the irreversible inhibition of human monoamine oxidases by ASS234, a multi-target compound designed for use in Alzheimer's disease. Biochim Biophys Acta, 1844 (6): 1104-10. [PMID:24642166]

6. Fowler CJ, Mantle TJ, Tipton KF. (1982) The nature of the inhibition of rat liver monoamine oxidase types A and B by the acetylenic inhibitors clorgyline, l-deprenyl and pargyline. Biochem Pharmacol, 31 (22): 3555-61. [PMID:6817759]

7. Haefely WE, Kettler R, Keller HH, Da Prada M. (1990) Ro 19-6327, a reversible and highly selective monoamine, oxidase B inhibitor: a novel tool to explore the MAO-B function in humans. Adv Neurol, 53: 505-12. [PMID:2122653]

8. Jagrat M, Behera J, Yabanoglu S, Ercan A, Ucar G, Sinha BN, Sankaran V, Basu A, Jayaprakash V. (2011) Pyrazoline based MAO inhibitors: synthesis, biological evaluation and SAR studies. Bioorg Med Chem Lett, 21 (14): 4296-300. [PMID:21680183]

9. Koch P, Akkari R, Brunschweiger A, Borrmann T, Schlenk M, Küppers P, Köse M, Radjainia H, Hockemeyer J, Drabczyńska A et al.. (2013) 1,3-Dialkyl-substituted tetrahydropyrimido[1,2-f]purine-2,4-diones as multiple target drugs for the potential treatment of neurodegenerative diseases. Bioorg Med Chem, 21 (23): 7435-52. [PMID:24139167]

10. Mishra N, Sasmal D. (2011) Development of selective and reversible pyrazoline based MAO-B inhibitors: virtual screening, synthesis and biological evaluation. Bioorg Med Chem Lett, 21 (7): 1969-73. [PMID:21377879]

11. Naoi M, Nomura Y, Ishiki R, Suzuki H, Nagatsu T. (1988) 4-(O-benzylphenoxy)-N-methylbutylamine (bifemelane) and other 4-(O-benzylphenoxy)-N-methylalkylamines as new inhibitors of type A and B monoamine oxidase. J Neurochem, 50 (1): 243-7. [PMID:3335842]

12. Phillips OA, D'Silva R, Bahta TO, Sharaf LH, Udo EE, Benov L, Eric Walters D. (2015) Synthesis and biological evaluation of novel 5-(hydroxamic acid)methyl oxazolidinone derivatives. Eur J Med Chem, 106: 120-31. [PMID:26536532]

13. Tetrud JW, Langston JW. (1989) The effect of deprenyl (selegiline) on the natural history of Parkinson's disease. Science, 245 (4917): 519-22. [PMID:2502843]

14. Toprakçí M, Yelekçi K. (2005) Docking studies on monoamine oxidase-B inhibitors: estimation of inhibition constants (K(i)) of a series of experimentally tested compounds. Bioorg Med Chem Lett, 15 (20): 4438-46. [PMID:16137882]

15. Yoshida S, Rosen TC, Meyer OG, Sloan MJ, Ye S, Haufe G, Kirk KL. (2004) Fluorinated phenylcyclopropylamines. Part 3: Inhibition of monoamine oxidase A and B. Bioorg Med Chem, 12 (10): 2645-52. [PMID:15110846]

16. Youdim MB, Gross A, Finberg JP. (2001) Rasagiline [N-propargyl-1R(+)-aminoindan], a selective and potent inhibitor of mitochondrial monoamine oxidase B. Br J Pharmacol, 132 (2): 500-6. [PMID:11159700]

17. Zreika M, Fozard JR, Dudley MW, Bey P, McDonald IA, Palfreyman MG. (1989) MDL 72,974: a potent and selective enzyme-activated irreversible inhibitor of monoamine oxidase type B with potential for use in Parkinson's disease. J Neural Transm Park Dis Dement Sect, 1 (4): 243-54. [PMID:2597310]

How to cite this page

Catecholamine turnover: Monoamine oxidase B. Last modified on 04/10/2021. Accessed on 18/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=2490.