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BioAssay: AID 463807

Clearance in CD1 mouse assessed as CHM-1-P levels at 10 mg/kg, iv

CHM-1 [2-(2-fluorophenyl)-6,7-methylenedioxyquinolin-4-one] (1) has a unique antitumor mechanism of action. However, because 1 has relatively low hydrophilicity, it was evaluated only via ip administration, which is not clinically acceptable. In this study, we synthesized the monosodium phosphate salt (CHM-1-P-Na, 4) of 1 as a hydrophilic prodrug. Compound 4 was rapidly converted into 1 following more ..
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 Tested Compounds
 Tested Compounds
All(1)
 
 
Unspecified(1)
 
 
 Tested Substances
 Tested Substances
All(1)
 
 
Unspecified(1)
 
 
 Related BioAssays
 Related BioAssays
AID: 463807
Data Source: ChEMBL (614670)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2010-09-27
Modify Date: 2014-05-27

Data Table ( Complete ):           View All Data
Tested Compound:
Description:
Title: Synthesis and preclinical evaluations of 2-(2-fluorophenyl)-6,7-methylenedioxyquinolin-4-one monosodium phosphate (CHM-1-P-Na) as a potent antitumor agent.

Abstract: CHM-1 [2-(2-fluorophenyl)-6,7-methylenedioxyquinolin-4-one] (1) has a unique antitumor mechanism of action. However, because 1 has relatively low hydrophilicity, it was evaluated only via ip administration, which is not clinically acceptable. In this study, we synthesized the monosodium phosphate salt (CHM-1-P-Na, 4) of 1 as a hydrophilic prodrug. Compound 4 was rapidly converted into 1 following iv and po administration and also possessed excellent antitumor activity in a SKOV-3 xenograft nude mice model. Compound 4 also had clear-cut pharmacological effects on enzymes related with tumor cells. Neither 4 nor 1 significantly affected normal biological function in a safety pharmacology profiling study. Compound 1 caused apoptotic effects in breast carcinoma cells via accumulation of cyclin B1, and importantly, the endogenous levels of the mitotic spindle checkpoint proteins BubR1 directly correlated with cellular response to microtubule disruption. With excellent antitumor activity profiles, 4 is highly promising for development as an anticancer clinical trials candidate.
(PMID: 20102207)
Comment
Putative Target:
ChEMBL Target ID: 50594
Target Type: ORGANISM
Pref Name: Mus musculus
Organism: Mus musculus
Tax ID: 10090
Confidence: Target assigned is non-molecular
Relationship Type: Non-molecular target assigned
Categorized Comment - additional comments and annotations
From ChEMBL:
Assay Type: ADME
Assay Data Source: Scientific Literature
BAO: Assay Format: organism-based format
Assay Test Type: In vivo
From MLP Probe Report:
Probe count: 1
MLP Probe ML# for probe 1: ML218
PubChem Substance ID (SID) for probe 1: 92310249
PubChem Compound ID (CID) for probe 1: 45115620
NCBI Book chapter link for probe 1: http://www.ncbi.nlm.nih.gov/books/NBK143195/ (ID: 3034046)
Grant number for probe 1: NS050771-01
PubMed Publication ID (PMID) for probe 1: 22368764
NCBI Book chapter title for probe 1: Scaffold Hopping Affords a Highly Selective in vitro and in vivo T-Type Calcium Inhibitor Probe Free From IP Issues
Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1CL activity commentCL activity commentString
2CL standard flagCL standard flagInteger
3CL qualifierCL qualifierString
4CL published valueCL published valueFloatml/min.Kg
5CL standard valueCL standard valueFloatmL.min-1.kg-1

Data Table (Concise)
Data Table ( Complete ):     View All Data
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