Monomethyl auristatin E

Source: Wikipedia, the free encyclopedia.
Monomethyl auristatin E
Names
IUPAC name
(S)-N-((3R,4S,5S)-1-((S)-2-((1R,2R)-3-(((1S,2R)-1-hydroxy-1-phenylpropan-2-yl)amino)-1-methoxy-2-methyl-3-oxopropyl)pyrrolidin-1-yl)-3-methoxy-5-methyl-1-oxoheptan-4-yl)-N,3-dimethyl-2-((S)-3-methyl-2-(methylamino)butanamido)butanamide
Other names
Monomethylauristatin E
Identifiers
3D model (
JSmol
)
Abbreviations MMAE
ChemSpider
ECHA InfoCard
 100.241.825 Edit this at Wikidata
KEGG
UNII
  • InChI=1S/C39H67N5O7/c1-13-25(6)34(43(10)39(49)33(24(4)5)42-38(48)32(40-9)23(2)3)30(50-11)22-31(45)44-21-17-20-29(44)36(51-12)26(7)37(47)41-27(8)35(46)28-18-15-14-16-19-28/h14-16,18-19,23-27,29-30,32-36,40,46H,13,17,20-22H2,1-12H3,(H,41,47)(H,42,48)/t25-,26+,27+,29-,30+,32-,33-,34-,35+,36+/m0/s1 ☒N
    Key: DASWEROEPLKSEI-UIJRFTGLSA-N ☒N
  • InChI=1/C39H67N5O7/c1-13-25(6)34(43(10)39(49)33(24(4)5)42-38(48)32(40-9)23(2)3)30(50-11)22-31(45)44-21-17-20-29(44)36(51-12)26(7)37(47)41-27(8)35(46)28-18-15-14-16-19-28/h14-16,18-19,23-27,29-30,32-36,40,46H,13,17,20-22H2,1-12H3,(H,41,47)(H,42,48)/t25-,26+,27+,29-,30+,32-,33-,34-,35+,36+/m0/s1
    Key: DASWEROEPLKSEI-UIJRFTGLBD
  • CO[C@H]([C@H](C(N[C@@H]([C@H](C1=CC=CC=C1)O)C)=O)C)[C@@]2([H])N(C(C[C@H]([C@H]([C@H](CC)C)N(C)C([C@H](C(C)C)NC([C@@H](NC)C(C)C)=O)=O)OC)=O)CCC2
Properties
C39H67N5O7
Molar mass 717.993 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
☒N verify (what is checkY☒N ?)

Monomethyl auristatin E (MMAE) is a synthetic

antimitotic drug derived from peptides occurring in marine shell-less mollusc Dolabella auricularia called dolastatins which show potent activity in preclinical studies, both in vitro and in vivo, against a range of lymphomas, leukemia and solid tumors. These drugs show potency of up to 200 times that of vinblastine, another antimitotic drug used for Hodgkin lymphoma as well as other types of cancer.[2]

MMAE is actually desmethyl-auristatin E; that is, the N-terminal

methyl substituent instead of two as in auristatin E itself.[2]

Mechanism of action

Monomethyl auristatin E is an

antimitotic agent which inhibits cell division by blocking the polymerisation of tubulin. The linker to the monoclonal antibody is stable in extracellular fluid, but is cleaved by cathepsin once the conjugate has entered a tumor cell, thus activating the antimitotic mechanism.[3][4]

Structure of a MMAE-MAB-conjugate. The linker, consisting of the amino acids valine (Val) and citrulline (Cit), is cleaved by cathepsin inside tumour cells.[5] The spacer (para-aminobenzylcarbamate) is marked green, the cathepsin-cleavable linker is blue, and the attachment group (consisting of maleimide and caproic acid) is brown. The whole radical inside the four boxes is called vedotin.

Monoclonal antibodies/ADCs

MMAE has been tested with various monoclonal antibodies (usually forming an

antibody-drug conjugate
).

Examples:

See also

References

  1. ^ Statement on a nonproprietary name adopted by the USAN Council: Vedotin
  2. ^
    PMID 22069744
    .
  3. ^ a b Seattle Genetics: Brentuximab vedotin (SGN-35) Archived 2011-07-16 at the Wayback Machine
  4. ^
    S2CID 25746938
    .
  5. ^ A. Klement (13 May 2013). "Sprunginnovation beim Hodgkin-Lymphom: Adcetris". Österreichische Apothekerzeitung (in German) (10/2013): 67f.
  6. ^ Medical News Today: CuraGen Announces Expansion Of CR011-vcMMAE Phase II Trial In Advanced Breast Cancer
  7. ^ NCI Drug Dictionary: Glembatumumab vedotin
  8. PMID 25934707
    .
  9. ^ A study of Escalating Doses of AGS67E Given as Monotherapy in Subjects With Refractory or Relapsed Lymphoid Malignancies
  10. S2CID 233223114
    .
  11. ^ Indusatumab vedotin (MLN-0264) Clinical Trials. March 2015
Retrieved from "https://en.wikipedia.org/w/index.php?title=Monomethyl_auristatin_E&oldid=1170044886"