Auristatin E - CAS 160800-57-7 Catalog number: BADC-00188

Description

Auristatin E is a synthetic analog of dolastatin 10. Auristatin E is a highly potent antimitotic agent.Auristatin E inhibits tubulin polymerization. Auristatin E is a cytotoxic tubulin modifier with potent and selective antitumor activity.

Synonyms

Auristatin E

IUPAC Name

(2S)-2-[[(2S)-2-(dimethylamino)-3-methylbutanoyl]amino]-N-[(3R,4S,5S)-1-[(2S)-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-dimethylbutanamide

Canonical SMILES

CCC(C)C(C(CC(=O)N1CCCC1C(C(C)C(=O)NC(C)C(C2=CC=CC=C2)O)OC)OC)N(C)C(=O)C(C(C)C)NC(=O)C(C(C)C)N(C)C

InChI

InChI=1S/C40H69N5O7/c1-14-26(6)35(44(11)40(50)33(24(2)3)42-39(49)34(25(4)5)43(9)10)31(51-12)23-32(46)45-22-18-21-30(45)37(52-13)27(7)38(48)41-28(8)36(47)29-19-16-15-17-20-29/h15-17,19-20,24-28,30-31,33-37,47H,14,18,21-23H2,1-13H3,(H,41,48)(H,42,49)/t26-,27+,28+,30-,31+,33-,34-,35-,36+,37+/m0/s1

InChIKey

WOWDZACBATWTAU-FEFUEGSOSA-N

Density

1.1±0.1 g/cm3

Solubility

Soluble in DMSO, not in water

Flash Point

480.6±34.3 °C

Index Of Refraction

1.519

LogP

4.75

Vapor Pressure

0.0±0.3 mmHg at 25°C

In Vivo

Two auristatin E-based albumin-binding drugs, AE-Keto-Sulf07 and AE-Ester-Sulf07 was describeed, which were designed to release the active compound at the tumor site in a pH-dependent manner. A panel of patient- and cell-derived human tumor xenograft models (melanoma A375, ovarian carcinoma A2780, non-small-cell lung cancer LXFA737 and LXFE937, and head and neck squamous cell carcinomas) were screened with starting tumor volumes in the range of either 130-150 mm3 (small tumors) or 270-380 mm3 (large tumors). Both albumin-binding prodrugs showed compelling anticancer efficacy compared to the parent drug auristatin E, inducing statistically significant long-term partial and/or complete tumor regressions. AE-Keto-Sulf07 displayed very good antitumor response over a wide dose range, 3.0-6.5 mg/kg (5-8 injections, biweekly). AE-Ester-Sulf07 was highly efficacious between 1.9 and 2.4 mg/kg (8 injections, biweekly) or at 3.8 mg/kg (4 injections, weekly), but caused cumulative skin irritation due to scratching and biting. In contrast at its MTD, auristatin E (0.3 mg/kg, 8 injections, biweekly) was only marginally active.

Clinical Trial Information

Application

ADCs Cytotoxin

Appearance

White to off-white solid

Purity

≥96.0% (HPLC)

Shelf Life

≥360 days if stored properly

Shipping

Room temperature, or blue ice upon request.

Storage

Dry, dark and at 0 - 4 °C for short term (days to weeks) or -20 °C for long term (months to years).

Pictograms

Health Hazard

Signal Word

Danger

Boiling Point

871.0±65.0 °C at 760 mmHg