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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:: The description was created based on several sources, including 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
Unknown

Approved Use

Unknown
PubMed

PubMed

TitleDatePubMed
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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