SOBLIDOTIN

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C39H67N5O6
Molecular Weight	701.9792
Optical Activity	UNSPECIFIED
Defined Stereocenters	8 / 8
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@]1(CCCN1C(=O)C[C@@H](OC)[C@H]([C@@H](C)CC)N(C)C(=O)[C@@H](NC(=O)[C@H](C(C)C)N(C)C)C(C)C)[C@H](OC)[C@@H](C)C(=O)NCCC2=CC=CC=C2

InChI

InChIKey=DZMVCVHATYROOS-ZBFGKEHZSA-N

InChI=1S/C39H67N5O6/c1-13-27(6)35(43(10)39(48)33(25(2)3)41-38(47)34(26(4)5)42(8)9)31(49-11)24-32(45)44-23-17-20-30(44)36(50-12)28(7)37(46)40-22-21-29-18-15-14-16-19-29/h14-16,18-19,25-28,30-31,33-36H,13,17,20-24H2,1-12H3,(H,40,46)(H,41,47)/t27-,28+,30-,31+,33-,34-,35-,36+/m0/s1

HIDE SMILES / InChI

Molecular Formula	C39H67N5O6
Molecular Weight	701.9792
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	8 / 8
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: http://www.ncbi.nlm.nih.gov/pubmed/16827132
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/16999818 and http://adisinsight.springer.com/drugs/800005682

Soblidotin is a derivative of dolastatin 10, which was isolated from the Indian Ocean sea hare, Dolabella auricularia, in 1987. Soblidotin inhibits tubulin polymerization, resulting in cell cycle arrest and induction of apoptosis. It has a broad spectrum of antitumor activity against various murine tumors – P388 leukemia, Colon26 and LLC carcinomas, B16 melanoma and M5076 sarcoma – as well as human tumor xenografts, MX-1, LX-1 and SBC-3 carcinomas. Soblidotin is currently undergoing clinical evaluation and, in phase II clinical trials for solid tumours.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
microtubule polymerization 20 Target ID: GO:0046785 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10920282	Inhibitor 8297	2.2 µM [IC50]
cell growth 21 Target ID: GO:0016049 Sources: http://www.ncbi.nlm.nih.gov/pubmed/16827132	Inhibitor 8297
Plasmodium falciparum growth 2 Target ID: Plasmodium falciparum growth Sources: https://www.ncbi.nlm.nih.gov/pubmed/12654761	Inhibitor 8297	2.0 nM [IC50]
Apoptosis 155 Target ID: map04210 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17473826	Activator 1430

Conditions

Condition	Modality	Targets	Highest Phase	Product
Metastatic soft tissue sarcoma 1 Sources: https://clinicaltrials.gov/ct2/show/NCT00064220	Primary		Phase II 1132	Unknown Approved Use Unknown
Metastatic non-small cell lung cancer 13 Sources: https://clinicaltrials.gov/ct2/show/NCT00061854	Primary		Phase II 1132	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Phase I and pharmacokinetic study of TZT-1027, a novel synthetic dolastatin 10 derivative, administered as a 1-hour intravenous infusion every 3 weeks in patients with advanced refractory cancer.	2004 Apr	15033678
Phase I and pharmacokinetic study of the dolastatin 10 analogue TZT-1027, given on days 1 and 8 of a 3-week cycle in patients with advanced solid tumors.	2005 May 15	15897580
Phase I study of TZT-1027, a novel synthetic dolastatin 10 derivative, for the treatment of patients with non-small cell lung cancer.	2008 Jun	18214483

Patents

Sample Use Guides

In Vivo Use Guide

The recommended dose for phase II studies of Soblidotin is 2.4 mg/m(2) given i.v. over 60 minutes, on days 1 and 8 every 21 days.

Route of Administration: Intravenous

In Vitro Use Guide

Treatment with 10(-7) g/mL Soblidotin rapidly disrupted the microtubule cytoskeleton in human umbilical vascular endothelial cells (HUVEC), and significantly enhanced vascular permeability in HUVEC monolayers.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:38:56 GMT 2023` Edited by `admin` on `Fri Dec 15 15:38:56 GMT 2023`
Record UNII	DQC51A0WQH
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

SOBLIDOTIN

Official Name

English

AURISTATIN PE

Brand Name

English

TZT-1027

Code

English

SOBLIDOTIN [JAN]

Common Name

English

soblidotin [INN]

Common Name

English

Soblidotin [WHO-DD]

Common Name

English

L-VALINAMIDE, N,N-DIMETHYL-L-VALYL-N-((1S,2R)-2-METHOXY-4-((2S)-2-((1R,2R)-1-METHOXY-2-METHYL-3-OXO-3-((2-PHENYLETHYL)AMINO)PROPYL)-1-PYRROLIDINYL)-1-((1S)-1-METHYLPROPYL)-4-OXOBUTYL)-N-METHYL-

Systematic Name

English

N(SUP 2)-(N,N-DIMETHYL-L-VALYL)-N(SUP 1)-((1S,2R)-2-METHOXY-4-((2S)-2-((1R,2R)-1-METHOXY-2-METHYL-3-OXO-3-((2-PHENYLETHYL)AMINO)PROPYL)-1-PYRROLIDINYL)-1-((1S)-1-METHYLPROPYL)-4-OXOBUTYL)-N1-METHYL-L-VALINAMIDE

Common Name

English

N2-(N,N-DIMETHYL-L-VALYL)-N1-((1S,2R)-2-METHOXY-4-((2S)-2-((1R,2R)-1-METHOXY-2-METHYL-3-OXO-3-((2-PHENYLETHYL)AMINO)PROPYL)-1-PYRROLIDINYL)-1-((1S)-1-METHYLPROPYL)-4-OXOBUTYL)-N1-METHYL-L-VALINAMIDE

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C1893