Monomethyl auristatin E

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
CAS Number	474645-27-7 N
3D model (JSmol)	Interactive image
Abbreviations	MMAE
ChemSpider	9716967 N
KEGG	D09691
PubChem CID	11542188
InChI 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
SMILES 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
Chemical formula	C39H67N5O7
Molar mass	717.99 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
N  (what is YN ?)
Infobox references

Monomethyl auristatin E (MMAE) is a synthetic antineoplastic agent. Because of its toxicity, it cannot be used as a drug itself; instead, it is linked to a monoclonal antibody (MAB) which directs it to the cancer cells. In International Nonproprietary Names for MMAE-MAB-conjugates, the name vedotin refers to MMAE plus its linking structure to the antibody. It is a potent 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.

MMAE is actually desmethyl-auristatin E; that is, the N-terminal amino group has only one methyl substituent instead of two as in auristatin E itself.

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 tumour cell, thus activating the antimitotic mechanism.

MMAE has been tested with various monoclonal antibodies (usually forming an antibody-drug conjugate).