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Details

Stereochemistry ABSOLUTE
Molecular Formula C39H67N5O7
Molecular Weight 717.9801
Optical Activity UNSPECIFIED
Defined Stereocenters 10 / 10
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of MONOMETHYL AURISTATIN E

SMILES

CC[C@]([H])(C)[C@@]([H])([C@@]([H])(CC(=O)N1CCC[C@@]1([H])[C@@]([H])([C@@]([H])(C)C(=N[C@]([H])(C)[C@]([H])(c2ccccc2)O)O)OC)OC)N(C)C(=O)[C@]([H])(C(C)C)N=C([C@]([H])(C(C)C)NC)O

InChI

InChIKey=DASWEROEPLKSEI-UIJRFTGLSA-N
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

HIDE SMILES / InChI

Molecular Formula C39H67N5O7
Molecular Weight 717.9801
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 10 / 10
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment:: https://www.ncbi.nlm.nih.gov/pubmed/19633198 | https://www.ncbi.nlm.nih.gov/pubmed/18809969 | https://www.ncbi.nlm.nih.gov/pubmed/28211277 | https://www.ncbi.nlm.nih.gov/pubmed/27795412

Monomethyl Auristatin E (MMAE) is an antimitotic agent which inhibits cell division by blocking the polymerization of tubulin. Monomethyl Auristatin E is the synthetic analog of the antineoplastic natural product Dolastatin 10, cannot be used as a drug itself. Monomethyl Auristatin E is commonly conjugated with monoclonal antibodies directed at antigens specific to cancer cells for tumor-directed cytotoxicity. MMAE is typically coupled to the antibody via a protease-cleavable linker, allowing separation of the drug from the antibody following intracellular localization. When coupled to cAC10, Monomethyl Auristatin E shows selective cytotoxicity in CD30+ cells and induces G2/M-phase growth arrest and cell death through the induction of apoptosis. When coupled to the anti-CD79b antibody, anti–CD79b-vcMMAE has very potent and broad activity across a large panel of NHL cell lines in vitro. When coupled to the anti-HER2 antibody, pertuzumab-vc-MMAE can also be effectively internalized and potently kill HER2 over-expressing tumor cells. In the Karpas 299 ALCL model, cAC10-vcMMAE induces complete, durable tumor regression, while free MMAE doesn’t produce detectable antitumor activity. In mouse xenograft models of NHL, anti–CD79b-vcMMAE strikingly results in sustained complete tumor remission.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
PubMed

PubMed

TitleDatePubMed
Tumor radiosensitization by monomethyl auristatin E: mechanism of action and targeted delivery.
2015 Apr 1
Patents

Sample Use Guides

Mice were treated with 0.36 mg/kg
Route of Administration: Intravenous
Cytotoxicity was measured using Alamar Blue (Biosource International, Camarillo, CA) dye reduction assay using CD30+ HD lines L540, KM-H2, HDLM-2, and L428 and the ALCL line Karpas 299 cell lines. Cells were plated at 5000 cells/well and were exposed to a graded titration of cAC10, cAC10-vcMMAE, or an isotype-matched irrelevant control immunoglobulin or its conjugate with vcMMAE. Cells were assessed for cytotoxicity by Alamar Blue assay after 96 hours of continuous exposure. A 40% solution (wt/vol) of Alamar Blue was freshly prepared in complete media just before cultures were added. Ninety-two hours after drug exposure, Alamar Blue solution was added to cells to constitute 10% culture volume. Cells were incubated for 4 hours, and dye reduction was measured on a Fusion HT fluorescent plate reader (Packard Instruments, Meriden, CT).
Substance Class Chemical
Created
by admin
on Fri Jun 25 20:34:41 UTC 2021
Edited
by admin
on Fri Jun 25 20:34:41 UTC 2021
Record UNII
V7I58RC5EJ
Record Status Validated (UNII)
Record Version
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Name Type Language
MONOMETHYL AURISTATIN E
Common Name English
SGD-1010
Code English
MONOMETHYLAURISTATIN E [MI]
Common Name English
MMAE
Common Name English
N-METHYL-L-VALYL-N-((1S,2R)-4-((2S)-2-((1R,2R)-3-(((1R,2S)-2-HYDROXY-1-METHYL-2-PHENYLETHYL)AMINO)-1-METHOXY-2-METHYL-3-OXOPROPYL)PYRROLIDIN-1-YL)-2-METHOXY-1-((1S)-1-METHYLPROPYL)-4-OXOBUTYL)-N-METHYL-L-VALINAMIDE
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C67422
Created by admin on Fri Jun 25 20:34:41 UTC 2021 , Edited by admin on Fri Jun 25 20:34:41 UTC 2021
FDA ORPHAN DRUG 643918
Created by admin on Fri Jun 25 20:34:41 UTC 2021 , Edited by admin on Fri Jun 25 20:34:41 UTC 2021
Code System Code Type Description
NCI_THESAURUS
C122637
Created by admin on Fri Jun 25 20:34:41 UTC 2021 , Edited by admin on Fri Jun 25 20:34:41 UTC 2021
PRIMARY
MERCK INDEX
M7610
Created by admin on Fri Jun 25 20:34:41 UTC 2021 , Edited by admin on Fri Jun 25 20:34:41 UTC 2021
PRIMARY Merck Index
CAS
474645-27-7
Created by admin on Fri Jun 25 20:34:41 UTC 2021 , Edited by admin on Fri Jun 25 20:34:41 UTC 2021
PRIMARY
PUBCHEM
11542188
Created by admin on Fri Jun 25 20:34:41 UTC 2021 , Edited by admin on Fri Jun 25 20:34:41 UTC 2021
PRIMARY
WIKIPEDIA
MONOMETHYL AURISTATIN E
Created by admin on Fri Jun 25 20:34:41 UTC 2021 , Edited by admin on Fri Jun 25 20:34:41 UTC 2021
PRIMARY
FDA UNII
V7I58RC5EJ
Created by admin on Fri Jun 25 20:34:41 UTC 2021 , Edited by admin on Fri Jun 25 20:34:41 UTC 2021
PRIMARY
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