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targets (23)
for drugs
Identification
Name Marimastat
Accession Number DB00786 (APRD00559)
Type small molecule
Groups approved
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
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Salts Not Available
Brand names
Name Company
Marimastat [Usan]
Brand mixtures Not Available
Categories
  • Antineoplastic Agents
  • Enzyme Inhibitors
CAS number 154039-60-8
Weight Average: 331.4079
Monoisotopic: 331.210721053
Chemical Formula C15H29N3O5
InChI Key InChIKey=OCSMOTCMPXTDND-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
Plain Text
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
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Polypeptides
  • Amino Ketones
  • Carboxylic Acids and Derivatives
  • Alcohols and Polyols
Substructures
  • Polypeptides
  • Hydroxy Compounds
  • Hydroxamic Acids
  • Amino Ketones
  • Carboxylic Acids and Derivatives
  • Carboxamides and Derivatives
  • Alcohols and Polyols
Pharmacology
Indication For the treatment of various cancers
Pharmacodynamics Used 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 action Marimastat 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.
Absorption Not Available
Volume of distribution Not Available
Protein binding Not Available
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
Pharmacoeconomics
Manufacturers Not Available
Packagers Not Available
Dosage forms Not Available
Prices Not Available
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
logP 0.4 Not Available
Predicted Properties
Property Value Source
water solubility 3.38e+00 g/l ALOGPS
logP 0.41 ALOGPS
logP -0.059 ChemAxon
logS -2 ALOGPS
pKa (strongest acidic) 8.61 ChemAxon
pKa (strongest basic) -1 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 5 ChemAxon
hydrogen donor count 5 ChemAxon
polar surface area 127.76 ChemAxon
rotatable bond count 8 ChemAxon
refractivity 84.2 ChemAxon
polarizability 34.99 ChemAxon
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
PubChem Compound 119031 Link_out
PubChem Substance 46505547 Link_out
ChemSpider 106358 Link_out
ChEBI 50662 Link_out
ChEMBL 50662 Link_out
Therapeutic Targets Database DCL000005 Link_out
PharmGKB PA164748329 Link_out
HET 097 Link_out
Wikipedia http://en.wikipedia.org/wiki/Marimastat Link_out
ATC Codes Not Available
AHFS Codes Not Available
PDB Entries
FDA label Not Available
MSDS Not Available
Interactions
Drug Interactions Not Available
Food Interactions Not Available
Targets

1. Interstitial collagenase

Pharmacological action: yes
Actions: inhibitor

Cleaves collagens of types I, II, and III at one site in the helical domain. Also cleaves collagens of types VII and X. In case of HIV infection, interacts and cleaves the secreted viral Tat protein, leading to a decrease in neuronal Tat's mediated neurotoxicity

Organism class: human
UniProt ID: P03956 Link_out
Gene: MMP1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: yes
Actions: inhibitor

In addition to gelatin and collagens, it cleaves KiSS1 at a Gly-|-Leu bond

Organism class: human
UniProt ID: P08253 Link_out
Gene: MMP2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: yes
Actions: antagonist

Can degrade fibronectin, laminin, gelatins of type I, III, IV, and V; collagens III, IV, X, and IX, and cartilage proteoglycans. Activates procollagenase

Organism class: human
UniProt ID: P08254 Link_out
Gene: MMP3 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: yes
Actions: antagonist

Degrades casein, gelatins of types I, III, IV, and V, and fibronectin. Activates procollagenase

Organism class: human
UniProt ID: P09237 Link_out
Gene: MMP7 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: yes
Actions: inhibitor

Can degrade fibrillar type I, II, and III collagens

Organism class: human
UniProt ID: P22894 Link_out
Gene: MMP8 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: yes
Actions: inhibitor

May play an essential role in local proteolysis of the extracellular matrix and in leukocyte migration. Could play a role in bone osteoclastic resorption. Cleaves KiSS1 at a Gly-|-Leu bond

Organism class: human
UniProt ID: P14780 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA

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

Pharmacological action: yes
Actions: antagonist

Can degrade fibronectin, gelatins of type I, III, IV, and V; weakly collagens III, IV, and V. Activates procollagenase

Organism class: human
UniProt ID: P09238 Link_out
Gene: MMP10 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: yes
Actions: antagonist

May play an important role in the progression of epithelial malignancies

Organism class: human
UniProt ID: P24347 Link_out
Gene: MMP11 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: yes
Actions: inhibitor

May be involved in tissue injury and remodeling. Has significant elastolytic activity. Can accept large and small amino acids at the P1' site, but has a preference for leucine. Aromatic or hydrophobic residues are preferred at the P1 site, with small hydrophobic residues (preferably alanine) occupying P3

Organism class: human
UniProt ID: P39900 Link_out
Gene: MMP12 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: yes
Actions: inhibitor

Degrades collagen type I. Does not act on gelatin or casein. Could have a role in tumoral process

Organism class: human
UniProt ID: P45452 Link_out
Gene: MMP13 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: yes
Actions: inhibitor

Seems to specifically activate progelatinase A. May thus trigger invasion by tumor cells by activating progelatinase A on the tumor cell surface

Organism class: human
UniProt ID: P50281 Link_out
Gene: MMP14 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: yes
Actions: inhibitor

Endopeptidase that degrades various components of the extracellular matrix. May activate progelatinase A

Organism class: human
UniProt ID: P51511 Link_out
Gene: MMP15 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: yes
Actions: inhibitor

Endopeptidase that degrades various components of the extracellular matrix, such as collagen type III and fibronectin. Activates progelatinase A. Involved in the matrix remodeling of blood vessels. The short isoform cleaves fibronectin and also collagen type III, but at lower rate. It has no effect on type I, II, IV and V collagen. However, upon interaction with CSPG4, it may be involved in degradation and invasion of type I collagen by melanoma cells

Organism class: human
UniProt ID: P51512 Link_out
Gene: MMP16 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: yes
Actions: inhibitor

Endopeptidase that degrades various components of the extracellular matrix, such as fibrin. May be involved in the activation of membrane-bound precursors of growth factors or inflammatory mediators, such as tumor necrosis factor-alpha. May also be involved in tumoral process. Not obvious if able to proteolytically activate progelatinase A. Does not hydrolyze collagen types I, II, III, IV and V, gelatin, fibronectin, laminin, decorin nor alpha1-antitrypsin

Organism class: human
UniProt ID: Q9ULZ9 Link_out
Gene: MMP17 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: yes
Actions: inhibitor

Endopeptidase that degrades various components of the extracellular matrix, such as aggrecan and cartilage oligomeric matrix protein (comp), during development, haemostasis and pathological conditions (arthritic disease). May also play a role in neovascularization or angiogenesis. Hydrolyzes collagen type IV, laminin, nidogen, nascin-C isoform, fibronectin, and type I gelatin

Organism class: human
UniProt ID: Q99542 Link_out
Gene: MMP19 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: yes
Actions: inhibitor

Degrades amelogenin, the major protein component of the enamel matrix and two of the macromolecules characterizing the cartilage extracellular matrix:aggrecan and the cartilage oligomeric matrix protein (COMP). May play a central role in tooth enamel formation

Organism class: human
UniProt ID: O60882 Link_out
Gene: MMP20 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: yes
Actions: inhibitor

May have an important and specific function in tumor progression and embryogenesis. Cleaves alpha-1-antitrypsin

Organism class: human
UniProt ID: Q8N119 Link_out
Gene: MMP21 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: yes
Actions: inhibitor

Protease

Organism class: human
UniProt ID: O75900 Link_out
Gene: MMP23A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: yes
Actions: inhibitor

Activates progelatinase A. May also be a proteoglycanase involved in degradation of proteoglycans, such as dermatan sulfate and chondroitin sulfate proteoglycans. Cleaves partially fibronectin, but not collagen type I, nor laminin (By similarity)

Organism class: human
UniProt ID: Q9Y5R2 Link_out
Gene: MMP24 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: yes
Actions: inhibitor

May activate progelatinase A

Organism class: human
UniProt ID: Q9NPA2 Link_out
Gene: MMP25 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: yes
Actions: inhibitor

May hydrolyze collagen type IV, fibronectin, fibrinogen, beta-casein, type I gelatin and alpha-1 proteinase inhibitor. Is also able to activates progelatinase B

Organism class: human
UniProt ID: Q9NRE1 Link_out
Gene: MMP26 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: yes
Actions: inhibitor

Matrix metalloproteinases degrade protein components of the extracellular matrix such as fibronectin, laminin, gelatins and/or collagens (By similarity)

Organism class: human
UniProt ID: Q9H306 Link_out
Gene: MMP27 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: yes
Actions: inhibitor

Can degrade casein. Could play a role in tissues homeostasis and repair

Organism class: human
UniProt ID: Q9H239 Link_out
Gene: MMP28 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19