ADOZELESIN

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C30H22N4O4
Molecular Weight	502.5201
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@]12C[C@@]13C(=CC(=O)C4=C3C(C)=CN4)N(C2)C(=O)C5=CC6=C(N5)C=CC(NC(=O)C7=CC8=C(O7)C=CC=C8)=C6

InChI

InChIKey=BYRVKDUQDLJUBX-JJCDCTGGSA-N

InChI=1S/C30H22N4O4/c1-15-13-31-27-22(35)11-25-30(26(15)27)12-18(30)14-34(25)29(37)21-9-17-8-19(6-7-20(17)33-21)32-28(36)24-10-16-4-2-3-5-23(16)38-24/h2-11,13,18,31,33H,12,14H2,1H3,(H,32,36)/t18-,30+/m1/s1

HIDE SMILES / InChI

Molecular Formula	C30H22N4O4
Molecular Weight	502.5201
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://adisinsight.springer.com/drugs/800000874 | https://www.ncbi.nlm.nih.gov/pubmed/7533669

Adozelesin (U 73975, adolezesin) is an experimental antitumor drug of the duocarmycin class. Adozelesin is a highly potent alkylating agent that undergoes binding in the minor groove of double-stranded DNA (ds-DNA) at A-T-rich sequences followed by covalent bonding with N-3 of adenine in preferred sequences. Adozelesin is therapeutically active against a broad spectrum of tumours and was in phase II clinical trials with Pharmacia Corporation (now Pfizer) in the US for breast cancer treatment. Phase I and Phase II clinical trials were conducted in 2000s, however, it was found adozelesin had marginal efficacy in the treatment of metastatic breast cancer at the dosage and schedule used.

Originator

Approval Year

PubMed

Title	Date	PubMed
Synergistic and additive combinations of several antitumor drugs and other agents with the potent alkylating agent adozelesin.	1995	7533669
Phase I trial of Adozelesin using the treatment schedule of daily x5 every 3 weeks.	1996	8824350
The DNA minor groove-alkylating cyclopropylpyrroloindole drugs adozelesin and bizelesin induce different DNA damage response pathways in human colon carcinoma HCT116 cells.	2003 Jul	12883038

Sample Use Guides

In Vivo Use Guide

Solid tumors: Adozelesin was given as a 10 minute IV infusion for 5 consecutive days every 21 days or upon recovery from toxicity. The dose range evaluated was 6-30 mcg/m2/day. The maximum tolerated dose was 30 mcg/m2/day. The recommended Phase II starting dose of Adozelesin using a 10 minute IV infusion for 5 consecutive days is 25 mcg/m2/day to be repeated every 4-6 weeks to allow recovery from myelotoxicity, based on our experience.

Route of Administration: Intravenous

In Vitro Use Guide

In human colon carcinoma HCT116 cells low adozelesin concentrations (e.g., 0.5 nM) induced a transient S-phase block and cell cycle arrest in G(2)-M, as well as increased induction of p53 and p21, whereas a high drug concentration (e.g., 2.5 nM) caused apoptosis but no p21 induction.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 17:28:34 GMT 2023` Edited by `admin` on `Sat Dec 16 17:28:34 GMT 2023`
Record UNII	6N3M4XJR2V
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ADOZELESIN

Official Name

English

NSC-615284

Code

English

adozelesin [INN]

Common Name

English

ADOZELESIN [USAN]

Common Name

English

(7BR,8AS)-N-(2-)((4,5,8,8A-TETRAHYDRO-7-METHYL-4-OXOCYCLOPROPA(C)PYRROLO(3,2-E)INDOL-2(1H)-YL)CARBONYL)INDOL-5-YL)-2-BENZOFURANCARBOXAMIDE

Common Name

English

U-73975

Code

English

2-BENZOFURANCARBOXAMIDE, N-(2-((4,5,8,8A-TETRAHYDRO-7-METHYL-4-OXOCYCLOPROPA(C)PYRROLO(3,2-E)INDOL-2(1H)-YL)CARBONYL)-1H-INDOL-5-YL)-, (7BR)-

Common Name

English

2-BENZOFURANCARBOXAMIDE, N-(2-(((7BR,8AS)-4,5,8,8A-TETRAHYDRO-7-METHYL-4-OXOCYCLOPROPA(C)PYRROLO(3,2-E)INDOL-2(1H)-YL)CARBONYL)-1H-INDOL-5-YL)-

Systematic Name

English

U-73,975

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C2156