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Identification
NameMarimastat
Accession NumberDB00786  (APRD00559)
TypeSmall Molecule
GroupsApproved, Investigational
Description

Used in the treatment of cancer, Marmiastat is an angiogenesis and metastasis inhibitor. As an angiogenesis inhibitor it limits the growth and production of blood vessels. As an antimetatstatic agent it prevents malignant cells from breaching the basement membranes.

Structure
Thumb
Synonyms
SynonymLanguageCode
BB-2516Not AvailableNot Available
MarimastatNot AvailableUSAN
Prescription ProductsNot Available
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
CAS number154039-60-8
WeightAverage: 331.4079
Monoisotopic: 331.210721053
Chemical FormulaC15H29N3O5
InChI KeyOCSMOTCMPXTDND-OUAUKWLOSA-N
InChI
InChI=1S/C15H29N3O5/c1-8(2)7-9(10(19)13(21)18-23)12(20)17-11(14(22)16-6)15(3,4)5/h8-11,19,23H,7H2,1-6H3,(H,16,22)(H,17,20)(H,18,21)/t9-,10+,11-/m1/s1
IUPAC Name
(2S,3R)-N'-[(1S)-2,2-dimethyl-1-(methylcarbamoyl)propyl]-N,2-dihydroxy-3-(2-methylpropyl)butanediamide
SMILES
CNC(=O)[C@@H](NC(=O)[C@H](CC(C)C)[C@H](O)C(=O)NO)C(C)(C)C
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as n-acyl-alpha amino acids and derivatives. These are compounds containing an alpha amino acid (or a derivative thereof) which bears an acyl group at its terminal nitrogen atom.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentN-acyl-alpha amino acids and derivatives
Alternative Parents
Substituents
  • N-acyl-alpha amino acid or derivatives
  • Alpha-amino acid amide
  • Fatty acyl
  • N-acyl-amine
  • Monosaccharide
  • Fatty amide
  • Secondary carboxylic acid amide
  • Secondary alcohol
  • Hydroxamic acid
  • Carboxamide group
  • Carboxylic acid amide
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Alcohol
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
Pharmacology
IndicationFor the treatment of various cancers
PharmacodynamicsUsed in the treatment of cancer, it is an angiogenesis and metastasis inhibitor. As an angiogenesis inhibitor it limits the growth and production of blood vessels. As an antimetatstatic agent it prevents malignant cells from breaching the basement membranes.
Mechanism of actionMarimastat is a broad spectrum matrix metalloprotease inhibitor. It mimics the peptide structure of natural MMP substrates and binds to matrix metalloproteases, thereby preventing the degradation of the basement membrane by these proteases. This antiprotease action prevents the migration of endothelial cells needed to form new blood vessels. Inhibition of MMPs also prevents the entry and exit of tumor cells into existing blood cells, thereby preventing metastasis.
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
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+0.516
Blood Brain Barrier+0.5834
Caco-2 permeable-0.6426
P-glycoprotein substrateNon-substrate0.5779
P-glycoprotein inhibitor INon-inhibitor0.7079
P-glycoprotein inhibitor IINon-inhibitor0.8359
Renal organic cation transporterNon-inhibitor0.9815
CYP450 2C9 substrateNon-substrate0.8498
CYP450 2D6 substrateNon-substrate0.8202
CYP450 3A4 substrateNon-substrate0.5449
CYP450 1A2 substrateNon-inhibitor0.8587
CYP450 2C9 substrateNon-inhibitor0.8594
CYP450 2D6 substrateNon-inhibitor0.8881
CYP450 2C19 substrateNon-inhibitor0.8108
CYP450 3A4 substrateNon-inhibitor0.8754
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9651
Ames testNon AMES toxic0.5559
CarcinogenicityNon-carcinogens0.6499
BiodegradationNot ready biodegradable0.9886
Rat acute toxicity2.5082 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9979
hERG inhibition (predictor II)Non-inhibitor0.9557
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
logP0.4Not Available
Predicted Properties
PropertyValueSource
Water Solubility3.38 mg/mLALOGPS
logP0.41ALOGPS
logP-0.059ChemAxon
logS-2ALOGPS
pKa (Strongest Acidic)8.61ChemAxon
pKa (Strongest Basic)-1ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count5ChemAxon
Polar Surface Area127.76 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity84.2 m3·mol-1ChemAxon
Polarizability34.99 Å3ChemAxon
Number of Rings0ChemAxon
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
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

1. Interstitial collagenase

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Interstitial collagenase P03956 Details

References:

  1. Heath EI, Grochow LB: Clinical potential of matrix metalloprotease inhibitors in cancer therapy. Drugs. 2000 May;59(5):1043-55. Pubmed
  2. Belotti D, Paganoni P, Giavazzi R: MMP inhibitors: experimental and clinical studies. Int J Biol Markers. 1999 Oct-Dec;14(4):232-8. Pubmed
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. 72 kDa type IV collagenase

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
72 kDa type IV collagenase P08253 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. Treharne GD, Boyle JR, Goodall S, Loftus IM, Bell PR, Thompson MM: Marimastat inhibits elastin degradation and matrix metalloproteinase 2 activity in a model of aneurysm disease. Br J Surg. 1999 Aug;86(8):1053-8. Pubmed
  3. Fanchon S, Bourd K, Septier D, Everts V, Beertsen W, Menashi S, Goldberg M: Involvement of matrix metalloproteinases in the onset of dentin mineralization. Eur J Oral Sci. 2004 Apr;112(2):171-6. Pubmed
  4. Bernardo MM, Brown S, Li ZH, Fridman R, Mobashery S: Design, synthesis, and characterization of potent, slow-binding inhibitors that are selective for gelatinases. J Biol Chem. 2002 Mar 29;277(13):11201-7. Epub 2002 Jan 14. Pubmed
  5. Shinoda K, Shibuya M, Hibino S, Ono Y, Matsuda K, Takemura A, Zou D, Kokubo Y, Takechi A, Kudoh S: A novel matrix metalloproteinase inhibitor, FYK-1388 suppresses tumor growth, metastasis and angiogenesis by human fibrosarcoma cell line. Int J Oncol. 2003 Feb;22(2):281-8. Pubmed
  6. Bourd-Boittin K, Fridman R, Fanchon S, Septier D, Goldberg M, Menashi S: Matrix metalloproteinase inhibition impairs the processing, formation and mineralization of dental tissues during mouse molar development. Exp Cell Res. 2005 Apr 1;304(2):493-505. Epub 2005 Jan 11. Pubmed

3. Stromelysin-1

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Stromelysin-1 P08254 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

4. Matrilysin

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Matrilysin P09237 Details

References:

  1. Heath EI, Grochow LB: Clinical potential of matrix metalloprotease inhibitors in cancer therapy. Drugs. 2000 May;59(5):1043-55. Pubmed
  2. Belotti D, Paganoni P, Giavazzi R: MMP inhibitors: experimental and clinical studies. Int J Biol Markers. 1999 Oct-Dec;14(4):232-8. Pubmed

5. Neutrophil collagenase

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Neutrophil collagenase P22894 Details

References:

  1. Heath EI, Grochow LB: Clinical potential of matrix metalloprotease inhibitors in cancer therapy. Drugs. 2000 May;59(5):1043-55. Pubmed
  2. Belotti D, Paganoni P, Giavazzi R: MMP inhibitors: experimental and clinical studies. Int J Biol Markers. 1999 Oct-Dec;14(4):232-8. Pubmed

6. Matrix metalloproteinase-9

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Matrix metalloproteinase-9 P14780 Details

References:

  1. Underwood CK, Min D, Lyons JG, Hambley TW: The interaction of metal ions and Marimastat with matrix metalloproteinase 9. J Inorg Biochem. 2003 Jun 1;95(2-3):165-70. Pubmed
  2. Nenan S, Lagente V, Planquois JM, Hitier S, Berna P, Bertrand CP, Boichot E: Metalloelastase (MMP-12) induced inflammatory response in mice airways: effects of dexamethasone, rolipram and marimastat. Eur J Pharmacol. 2007 Mar 15;559(1):75-81. Epub 2006 Dec 12. Pubmed
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

7. Stromelysin-2

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Stromelysin-2 P09238 Details

References:

  1. Heath EI, Grochow LB: Clinical potential of matrix metalloprotease inhibitors in cancer therapy. Drugs. 2000 May;59(5):1043-55. Pubmed
  2. Belotti D, Paganoni P, Giavazzi R: MMP inhibitors: experimental and clinical studies. Int J Biol Markers. 1999 Oct-Dec;14(4):232-8. Pubmed

8. Stromelysin-3

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Stromelysin-3 P24347 Details

References:

  1. Heath EI, Grochow LB: Clinical potential of matrix metalloprotease inhibitors in cancer therapy. Drugs. 2000 May;59(5):1043-55. Pubmed
  2. Belotti D, Paganoni P, Giavazzi R: MMP inhibitors: experimental and clinical studies. Int J Biol Markers. 1999 Oct-Dec;14(4):232-8. Pubmed

9. Macrophage metalloelastase

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Macrophage metalloelastase P39900 Details

References:

  1. Heath EI, Grochow LB: Clinical potential of matrix metalloprotease inhibitors in cancer therapy. Drugs. 2000 May;59(5):1043-55. Pubmed
  2. Belotti D, Paganoni P, Giavazzi R: MMP inhibitors: experimental and clinical studies. Int J Biol Markers. 1999 Oct-Dec;14(4):232-8. Pubmed

10. Collagenase 3

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Collagenase 3 P45452 Details

References:

  1. Heath EI, Grochow LB: Clinical potential of matrix metalloprotease inhibitors in cancer therapy. Drugs. 2000 May;59(5):1043-55. Pubmed
  2. Belotti D, Paganoni P, Giavazzi R: MMP inhibitors: experimental and clinical studies. Int J Biol Markers. 1999 Oct-Dec;14(4):232-8. Pubmed

11. Matrix metalloproteinase-14

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Matrix metalloproteinase-14 P50281 Details

References:

  1. Heath EI, Grochow LB: Clinical potential of matrix metalloprotease inhibitors in cancer therapy. Drugs. 2000 May;59(5):1043-55. Pubmed
  2. Belotti D, Paganoni P, Giavazzi R: MMP inhibitors: experimental and clinical studies. Int J Biol Markers. 1999 Oct-Dec;14(4):232-8. Pubmed

12. Matrix metalloproteinase-15

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Matrix metalloproteinase-15 P51511 Details

References:

  1. Heath EI, Grochow LB: Clinical potential of matrix metalloprotease inhibitors in cancer therapy. Drugs. 2000 May;59(5):1043-55. Pubmed
  2. Belotti D, Paganoni P, Giavazzi R: MMP inhibitors: experimental and clinical studies. Int J Biol Markers. 1999 Oct-Dec;14(4):232-8. Pubmed

13. Matrix metalloproteinase-16

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Matrix metalloproteinase-16 P51512 Details

References:

  1. Heath EI, Grochow LB: Clinical potential of matrix metalloprotease inhibitors in cancer therapy. Drugs. 2000 May;59(5):1043-55. Pubmed
  2. Belotti D, Paganoni P, Giavazzi R: MMP inhibitors: experimental and clinical studies. Int J Biol Markers. 1999 Oct-Dec;14(4):232-8. Pubmed

14. Matrix metalloproteinase-17

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Matrix metalloproteinase-17 Q9ULZ9 Details

References:

  1. Heath EI, Grochow LB: Clinical potential of matrix metalloprotease inhibitors in cancer therapy. Drugs. 2000 May;59(5):1043-55. Pubmed
  2. Belotti D, Paganoni P, Giavazzi R: MMP inhibitors: experimental and clinical studies. Int J Biol Markers. 1999 Oct-Dec;14(4):232-8. Pubmed

15. Matrix metalloproteinase-19

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Matrix metalloproteinase-19 Q99542 Details

References:

  1. Heath EI, Grochow LB: Clinical potential of matrix metalloprotease inhibitors in cancer therapy. Drugs. 2000 May;59(5):1043-55. Pubmed
  2. Belotti D, Paganoni P, Giavazzi R: MMP inhibitors: experimental and clinical studies. Int J Biol Markers. 1999 Oct-Dec;14(4):232-8. Pubmed

16. Matrix metalloproteinase-20

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Matrix metalloproteinase-20 O60882 Details

References:

  1. Heath EI, Grochow LB: Clinical potential of matrix metalloprotease inhibitors in cancer therapy. Drugs. 2000 May;59(5):1043-55. Pubmed
  2. Belotti D, Paganoni P, Giavazzi R: MMP inhibitors: experimental and clinical studies. Int J Biol Markers. 1999 Oct-Dec;14(4):232-8. Pubmed

17. Matrix metalloproteinase-21

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Matrix metalloproteinase-21 Q8N119 Details

References:

  1. Heath EI, Grochow LB: Clinical potential of matrix metalloprotease inhibitors in cancer therapy. Drugs. 2000 May;59(5):1043-55. Pubmed
  2. Belotti D, Paganoni P, Giavazzi R: MMP inhibitors: experimental and clinical studies. Int J Biol Markers. 1999 Oct-Dec;14(4):232-8. Pubmed

18. Matrix metalloproteinase-23

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Matrix metalloproteinase-23 O75900 Details

References:

  1. Heath EI, Grochow LB: Clinical potential of matrix metalloprotease inhibitors in cancer therapy. Drugs. 2000 May;59(5):1043-55. Pubmed
  2. Belotti D, Paganoni P, Giavazzi R: MMP inhibitors: experimental and clinical studies. Int J Biol Markers. 1999 Oct-Dec;14(4):232-8. Pubmed

19. Matrix metalloproteinase-24

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Matrix metalloproteinase-24 Q9Y5R2 Details

References:

  1. Heath EI, Grochow LB: Clinical potential of matrix metalloprotease inhibitors in cancer therapy. Drugs. 2000 May;59(5):1043-55. Pubmed
  2. Belotti D, Paganoni P, Giavazzi R: MMP inhibitors: experimental and clinical studies. Int J Biol Markers. 1999 Oct-Dec;14(4):232-8. Pubmed

20. Matrix metalloproteinase-25

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Matrix metalloproteinase-25 Q9NPA2 Details

References:

  1. Heath EI, Grochow LB: Clinical potential of matrix metalloprotease inhibitors in cancer therapy. Drugs. 2000 May;59(5):1043-55. Pubmed
  2. Belotti D, Paganoni P, Giavazzi R: MMP inhibitors: experimental and clinical studies. Int J Biol Markers. 1999 Oct-Dec;14(4):232-8. Pubmed

21. Matrix metalloproteinase-26

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Matrix metalloproteinase-26 Q9NRE1 Details

References:

  1. Heath EI, Grochow LB: Clinical potential of matrix metalloprotease inhibitors in cancer therapy. Drugs. 2000 May;59(5):1043-55. Pubmed
  2. Belotti D, Paganoni P, Giavazzi R: MMP inhibitors: experimental and clinical studies. Int J Biol Markers. 1999 Oct-Dec;14(4):232-8. Pubmed

22. Matrix metalloproteinase-27

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Matrix metalloproteinase-27 Q9H306 Details

References:

  1. Heath EI, Grochow LB: Clinical potential of matrix metalloprotease inhibitors in cancer therapy. Drugs. 2000 May;59(5):1043-55. Pubmed
  2. Belotti D, Paganoni P, Giavazzi R: MMP inhibitors: experimental and clinical studies. Int J Biol Markers. 1999 Oct-Dec;14(4):232-8. Pubmed

23. Matrix metalloproteinase-28

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Matrix metalloproteinase-28 Q9H239 Details

References:

  1. Heath EI, Grochow LB: Clinical potential of matrix metalloprotease inhibitors in cancer therapy. Drugs. 2000 May;59(5):1043-55. Pubmed
  2. Belotti D, Paganoni P, Giavazzi R: MMP inhibitors: experimental and clinical studies. Int J Biol Markers. 1999 Oct-Dec;14(4):232-8. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:12