5.00495

RubR1 Activator, GF-15

• Synonym(s): RubR1 Activator, GF-15, Supernumerary Centrosomes Clustering Inhibitor, 2ʹ-Benzyloxy-2ʹ-demethoxygriseofulvin, (2 S,6ʹ R)-(7-Chloro-4,6-dimethoxy-benzofuran-3-on)-2-spiro-1ʹ-(2ʹ-benzyloxy-6ʹ-methylcyclohex-2ʹ-en-4ʹ-one), (2, Supernumerary Centrosomes Clustering Inhibitor, 2ʹ-Benzyloxy-2ʹ-demethoxygriseofulvin, (2S,6ʹR)-(7-Chloro-4,6-dimethoxy-benzofuran-3-on)-2-spiro-1ʹ-(2ʹ-benzyloxy-6ʹ-methylcyclohex-2ʹ-en-4ʹ-one), (2S
• Empirical Formula (Hill Notation): C₂₃H₂₁ClO₆
• CAS Number: 888042-13-5
• Molecular Weight: 428.86
• UNSPSC Code: 12352200
• NACRES: NA.77

Properties

• Assay: ≥98% (HPLC)
• Quality Level: 100
• form: solid
• manufacturer/tradename: Calbiochem^®
• storage condition: OK to freeze; protect from light
• color: white
• solubility: DMSO: 50 mg/mL
• storage temp.: 2-8°C

Description

General description

A cell-permeable 2′-benzyloxy griseofulvin derivative that displays enhanced mammalian cancer-selective toxicity (IC₅₀ ≤2, ≤4, ≤12, and ≥30 µM against panels of leukemia, myeloma, solid tumors, and non-malignant cell lines, respectively), but little antifungal activity, by activating spindle-assembly-checkpoint (Pos. vs. Neg. RubR1 staining of metaphase PC-3 kinetophores with or without 24 h 0.75 µM GF-15 treatment) without affecting microtubule kinetochore attachment (Neg. Mad2 staining of metaphase PC-3 kinetophores with or without GF-15). Cancer cells are reported to undergo multipolar (MP) mitosis with normal or supernumerary centrosomes (Aberrant vs. declustered, respectively) in the presence of GF-15 (%Declustered / %Aberrant MP mitotic cells among all anaphase cells = 5.6/&lt0.5, 10/3.9, 16/18, 28/30, respectively, in PC-3 cultures treated with 0, 0.375, 0.75, or 1.5 µM GF-15 for 24 h), resulting in subsequent apoptotic cell death. Shown to retard OPM2 myeloma- and HT29 colon cancer-derived tumor expansion in mice (by 49% and 56%, respectively at the end of 2-wk treatment; 10 i.p. dosages at 20 mg/kg/day in 2 weeks) in vivo. Based on stability data obtained with its p-iodobenzyl analogue, GF-15 half-life is expected to be least 48 h in cultures.

A cell-permeable 2′-benzyloxy griseofulvin derivative that displays enhanced mammalian cancer-selective toxicity (IC₅₀ ≤2, ≤4, ≤12, and ≥30 µM against panels of leukemia, myeloma, solid tumors, and non-malignant cell lines, respectively), but little antifungal activity, by activating spindle-assembly-checkpoint without affecting microtubule kinetochore attachment. Cancer cells are reported to undergo multipolar (MP) mitosis with normal or supernumerary centrosomes in the presence of GF-15, resulting in subsequent apoptotic cell death. Shown to retard HT29 colon cancer & OPM2 myeloma tumor expansion in mice (20 mg/kg/day i.p.) in vivo. GF-15 half-life is expected to be least 48 h in cultures.

Please note that the molecular weight for this compound is batch-specific due to variable water content. Please refer to the vial label or the certificate of analysis for the batch-specific molecular weight. The molecular weight provided represents the baseline molecular weight without water.

Biochem/physiol Actions

Cell permeable: yes

Reversible: yes

Packaging

Packaged under inert gas

Warning

Toxicity: Standard Handling (A)

Reconstitution

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.

Other Notes

Raab, M.S., et al. 2012. Cancer Res.72, 5374.
Ronnest, M.H., et al. 2009. J. Med. Chem.52, 3342.
Crosse, R., et al. 1964. J. Gen. Microbiol.34, 51.

Legal Information

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Safety Information

• Storage Class Code: 11 - Combustible Solids
• WGK: WGK 2
• Flash Point(F): Not applicable
• Flash Point(C): Not applicable