Adolezesin - CAS 110314-48-2
Catalog number: 110314-48-2
Category: Inhibitor
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Molecular Formula:
C30H22N4O4
Molecular Weight:
502.52
COA:
Inquire
Targets:
Others
Description:
Adozelesin is an experimental antitumor drug of the duocarmycin class. It is the first of a class of DNA-sequence-selective alkylating agents. It binds to and alkylates DNA, resulting in a reduction of both cellular and simian virus 40 (SV40) DNA replication which ultimately reduces the rate of cancer growth. It has marginal efficacy in the treatment of metastatic breast cancer at the dosage and schedule used in clinic phase 1 and 2 trials. It was developed by Pharmacia and was terminated in clinic phase 2 trials.
Purity:
>98%
Appearance:
Solid powder
Synonyms:
U73975;U-73975;N-(2-((7bR,8aS)-7-methyl-4-oxo-1,2,4,5,8,8a-hexahydrocyclopropa[c]pyrrolo[3,2-e]indole-2-carbonyl)-1H-indol-5-yl)benzofuran-2-carboxamide
Solubility:
10 mM in DMSO
Storage:
-20°C Freezer
MSDS:
Inquire
Application:
Adozelesin has marginal efficacy in the treatment of metastatic breast cancer.
Quality Standard:
In-house standard
Shelf Life:
2 month in rt, long time
Quantity:
Milligrams-Grams
Boiling Point:
766.2±60.0 °C | Condition: Press: 760 Torr
Density:
1.56±0.1 g/cm3 | Condition: Temp: 20 °C Press: 760 Torr
InChIKey:
BYRVKDUQDLJUBX-JJCDCTGGSA-N
InChI:
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
Canonical SMILES:
CC1=CNC2=C1C34CC3CN(C4=CC2=O)C(=O)C5=CC6=C(N5)C=CC(=C6)NC(=O)C7=CC8=CC=CC=C8O7
Current Developer:
Adozelesin was developed by Pharmacia and was terminated in clinic phase 2 trials.
1.In vivo mutagenesis induced by CC-1065 and adozelesin DNA alkylation in a transgenic mouse model.
Monroe TJ;Mitchell MA Cancer Res. 1993 Dec 1;53(23):5690-6.
Although considerable work has focused on characterizing the bonding chemistry and sequence selective alkylation of DNA by cyclopropylpyrroloindole compounds, little is known about the molecular consequence of their N-3-adenine adducts in whole animal systems. We have utilized a transgenic mouse system, harboring a lambda phage shuttle vector, to assess the mutagenic potential of the antitumor compounds CC-1065 and adozelesin and, for the first time, to track the in vivo fate of their unique DNA modifications at the nucleotide level. Mice were inoculated with a single therapeutic dose of these agents and sacrificed at either 18 h, 3 days, or 15 days for extraction and analysis of liver DNA. Mutant frequencies obtained from drug treated and control animals were determined by in vitro packaging of the phage vector from genomic DNA followed by a colorimetric plaque assay to screen for phage in which the accompanying lacI repressor gene had mutated. Although undetectable at 18 h posttreatment, by 72 h a 3-fold increase in mutant frequency was observed in drug treated animals such that sequence analysis of drug induced mutations could be performed and a direct comparison made between in vitro and in vivo DNA alkylation.
2.Evaluation of the antineoplastic activity of adozelesin alone and in combination with 5-aza-2'-deoxycytidine and cytosine arabinoside on DLD-1 human colon carcinoma cells.
Côté S;Momparler RL Anticancer Drugs. 1993 Jun;4(3):327-33.
Adozelesin (Ado), a CC-1065 analog, shows significant antineoplastic activity in vivo against several types of murine tumors and human tumor xenografts. Ado is a DNA alkylating agent. One objective of this study was to investigate the cytotoxic action of Ado against the human colon (HT-29, DLD-1) and the lung (SK) carcinoma cell lines. The concentrations of Ado that produced 50% cell kill for a 4 and 24 h exposure were in the range of 0.001-0.02 ng/ml for both colon and lung carcinoma cells, indicating that this analog was a very potent cytotoxic agent. Since most clinical regimens for tumor therapy consist of several drugs, we investigated the antineoplastic action of Ado in combination with 5-aza-2'-deoxycytidine (5-Aza-CdR), a potent inhibitor of DNA methylation or cytosine arabinoside (Ara-C), a potent inhibitor of DNA synthesis. The Ado plus 5-Aza-CdR combination showed a synergistic effect on cytotoxicity of DLD-1 colon carcinoma cells for both a 6 and 24 h exposure. However, combination of Ado and Ara-C for a 6 h exposure showed an antagonistic effect, whereas a 24 h exposure showed a synergistic effect. These preclinical results provide some preliminary data on possible drugs that can be selected for use in combination with Ado in future clinical trials in patients with cancer.
3.Synthesis, cytotoxicity, antitumor activity and sequence selective binding of two pyrazole analogs structurally related to the antitumor agents U-71,184 and adozelesin.
Baraldi PG;Cacciari B;Romagnoli R;Spalluto G;Gambari R;Bianchi N;Passadore M;Ambrosino P;Mongelli N;Cozzi P;Geroni C Anticancer Drug Des. 1997 Oct;12(7):555-76.
Two pyrazole analogs structurally related to the antitumor agents adozelesin and U-71,184 respectively were synthesized. By using a polymerase chain reaction approach, both compounds show selective binding to A + T rich sequences exactly as reference compound U-71,184. In in vitro assays, against L1210 cell lines, both derivatives showed cytotoxicity in the pM range, values comparable with the natural target compound (+)-CC-1065. The most active compound showed very high antitumor activity in mice implanted with L1210 cells (ILS% 363).
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CAS 110314-48-2 Adolezesin

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