(S)-10-Hydroxycamptothecin

Catalog No.S2423 Synonyms: 10-HCPT

(S)-10-Hydroxycamptothecin Chemical Structure

Molecular Weight(MW): 364.35

10-Hydroxycamptothecin is a DNA topoisomerase I inhibitor with potent anti-tumor activity.

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Biological Activity

Description 10-Hydroxycamptothecin is a DNA topoisomerase I inhibitor with potent anti-tumor activity.
Targets
DNA topoisomerase I [1]
In vitro

10-Hydroxycamptothecin inhibits the growth of BT-20 and MDA-231 cell with IC50 of 34.3 nM and 7.27 nM, respectively, more potently than camptothecin (CPT) with IC50 of >500 nM. 10-Hydroxycamptothecin potently induces human topoisomerase I-mediated cleavable complex formation of pBR322 plasmid DNA with EC50 of 0.35 μM, displaying >50-fold potency than CPT with EC50 of 18.85 μM. [2] 10-Hydroxycamptothecin treatment induces dose-dependent growth inhibition of human microvascular endothelial cells (HMEC) with IC50 of 0.31 μM, and significantly inhibits the migration of HMEC with IC50 of 0.63 μM. Treatment of HMEC cells with 10-Hydroxycamptothecin also results in a dose-dependent inhibition of tube formation with IC50 of 0.96 μM. [3] 10-Hydroxycamptothecin (5-20 nM) significantly inhibits the proliferation of Colo 205 cells, arrests the cells in the G2 phase of the cell cycle and induces apoptosis through a caspase-3-dependent pathway. [4]

In vivo 10-Hydroxycamptothecin treatment inhibits angiogenesis in a concentration-dependent fashion in the CAM model, with 95% inhibition at dose of 25 nM, more potently than suramin which at 125 nM inhibits angiogenesis only by 60%. [3] Oral administration of 10-Hydroxycamptothecin at low doses of 2.5-7.5 mg/kg every 2 days leads to significant growth inhibition of Colo 205 xenografts in mice without acute toxicity. [4] LD50: Mice 104mg/kg (i.p.). [5]

Protocol

Cell Research:[2]
+ Expand
  • Cell lines: MDA-231, and BT-20 cells
  • Concentrations: Dissolved in DMSO, final concentrations ~50 μM
  • Incubation Time: 72 hours
  • Method: Cells are exposed to various concentrations of 10-Hydroxycamptothecin for 72 hours. Cell growth is monitored by the standard MTT assay.
    (Only for Reference)
Animal Research:[4]
+ Expand
  • Animal Models: BALB/c-nu mice transplanted subcutaneously with Colo 205 cells
  • Formulation: Dissolved in propylene glycol
  • Dosages: ~7.5 mg/kg
  • Administration: Orally once per two days
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 8 mg/mL warmed (21.95 mM)
Water Insoluble
Ethanol Insoluble
In vivo Add solvents to the product individually and in order(Data is from Selleck tests instead of citations):
30% PEG400+0.5% Tween80+5% propylene glycol
For best results, use promptly after mixing.
30 mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 364.35
Formula

C20H16N2O5

CAS No. 19685-09-7
Storage powder
in solvent
Synonyms 10-HCPT

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Clinical Trial Information

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT00046540 Completed Neoplasms INSYS Therapeutics Inc October 2002 Phase 1

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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Topoisomerase Signaling Pathway Map

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID