MonoMethyl auristatin E Chemical Properties

Melting point:

>90°C (dec.)

Boiling point:

873.5±65.0 °C(Predicted)

Density 

1.088±0.06 g/cm3(Predicted)

storage temp. 

-20°C Freezer

solubility 

DMSO (Slightly), Methanol (Slightly, Sonicated)

pka

13.66±0.20(Predicted)

form 

Solid

color 

White to Off-White

InChI

InChI=1S/C39H67N5O7/c1-13-25(6)34(43(10)33(24(4)5)39(49)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,42,48,49)/t25-,26+,27+,29-,30+,32-,33-,34-,35+,36+/m0/s1

InChIKey

RJACXSRFJLSJEZ-UIJRFTGLSA-N

SMILES

C(NC(=O)[C@H](C(C)C)NC)(=O)[C@H](C(C)C)N([C@@H]([C@@H](C)CC)[C@H](OC)CC(N1CCC[C@H]1[C@H](OC)[C@@H](C)C(N[C@H](C)[C@@H](O)C1=CC=CC=C1)=O)=O)C

CAS DataBase Reference

474645-27-7

MonoMethyl auristatin E Usage And Synthesis

Description

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. Monomethyl auristatin E or MMAE is 100-1000 times more potent than doxorubicin. It is a very potent antimitotic agent that inhibits cell division by blocking the polymerization of tubulin.

Chemical Properties

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.

Uses

MMAE is an effective and synthetic cytotoxic analog of Dolastatin 10 which is a potent antimitotic polypeptide isolated from a marine animal.

Uses

Dolastatin 10 is a natural antimitotic and antineoplastic agent that binds to tubulin and inhibits tubulin polymerization. Monomethyl Auristatin E (MMAE) is a synthetic analog of dolastatin 10 that similarly inhibits tubulin polymerization and exhibits potent cytotoxicity. It 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.[Cayman Chemical]

Biological Activity

monomethyl auristatin e(mmae) is a potent antimitotic agent by blocking the polymerisation of tubulin.microtubules play essential role in the function of the cell. microtubules are also reported to be involved in migration, transport and reorganization and have numerous dynamic roles including movement through motor proteins such as dynein and kinesin and the separation and segregation ofchromosomes during cell division.

Biochem/physiol Actions

Monomethyl Auristatin E (MMAE) is a highly potent peptidyl antimitotic agent that blocks the polymerization of tubulin. Monomethyl Auristatin E is a component of a clinically approved antibodydirected conjugates Brentuximab vedotin, Glembatumumab vedotin, Enfortumab vedotin and Polatuzumab vedotin.

in vitro

the cytotoxic effects of the mmae conjugates on h3396 cells were determined using both pulsed and long-term drug exposure assays. it was found that under both exposure conditions, high degrees of immunological specificity were obtained with the val-cit conjugates. cbr96-val-cit-mmae was highly active at <1/100th of the concentration required for antigen saturation [1].

in vivo

in vivo therapy tests were undertaken in athymic mice with subcutaneous l2987 human lung adenocarcinoma xenografts. mmae conjugates were administered at 3 mg mab component/kg/dose. all of the tested mmae conjugates were highly efficacious, leading to long-term regressions of established tumors, whereas the nonbinding control conjugates had no effect on tumor growth. in addition, there were no apparent toxicities associated with conjugate treatment [1].

IC 50

less than 1 nm for various cancer cell lines

References

[1] doronina so,toki be,torgov my,mendelsohn ba,cerveny cg,chace df,deblanc rl,gearing rp,bovee td,siegall cb,francisco ja,wahl af,meyer dl,senter pd. development of potent monoclonal antibody auristatin conjugates for cancer therapy. nat biotechnol.2003 jul;21(7):778-84.
[2] jian xu*, priya agarwal, ola saad, et al. clinical pharmacokinetics (pk) of anti-muc16 antibody-drug conjugates (adcs), dmuc5754a, in patients with platinum-resistant ovarian cancer: results from phase i study. this poster was presented at world adc summit 2014.

MonoMethyl auristatin E(474645-27-7)Related Product Information

• Ethanol
• Ozone
• Acrylic acid
• Feed Mould inhibitor
• Polyethylene
• L-Threonine
• Potassium pyrophosphate
• FARNESENE
• MonoMethylauristatin F
• (2R,3R)-N-((1S,2R)-1-hydroxy-1-phenylpropan-2-yl)-3-Methoxy-2-Methyl-3-((S)-pyrrolidin-2-yl)propanaMide (hydrochloride)
• VcMMAE
• N-Boc-(2R,3R,4S)-dolaproine
• (9H-fluoren-9-yl)Methyl ((S)-1-(((S)-1-(((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)(Methyl)aMino)-3-Methyl-1-oxobutan-2-yl)aMino)-3-Met
• (3R,4S,5S)-tert-butyl 3-Methoxy-5-Methyl-4-(MethylaMino)heptanoate hydroc hloride
• Valine
• Ethylene glycol
• Organic acid