Sigma-Aldrich Bmi-1 Expression Inhibitor

Assay

≥95% (HPLC)

Quality Level

100

Form

powder

Manufacturer/Tradename

Calbiochem^®

Storage Condition

OK to freeze
protect from light

Color

light yellow

Solubility

DMSO: 100 mg/mL

Storage Temp.

2-8°C

Inchi

1S/C17H13Br2N5OS/c1-9-15(24-5-3-4-20-16(24)21-9)13-8-26-17(22-13)23-14-11(18)6-10(25-2)7-12(14)19/h3-8H,1-2H3,(H,22,23)

Inchi Key

XVOOCQSWCCRVDY-UHFFFAOYSA-N

General Description

A cell-permeable imidazopyrimidinyl-thiazolamine compound that effectively downregulates cellular BMI-1 protein level both in culturesin vitro(IC₅₀= 0.5 µM/48 H/HT1080 and <0.37 µM/HCT116/overnight) and in micein vivo(4.5 ng vs.13.7 ng per mg HT1080 tumor tissue, respectively, with or without 10-d 60 mg/kg/d treatment via s.c.) by inhibiting BMI-1 transcription (IC₅₀= 0.5 µM against overnight reporter transcription in HEK293) via a yet unidentified mechanism, thereby reducing BMI-1-dependent RING1A E3 ligase activity and RING1A-mediated H2A ubiquitination (uH2A)/epigenetic regulations. Shown to exhibit antiproliferation activity against human colon cancer cells both in cultures (IC₅₀<300 nM against LS174T and primary colon cancer cultures)in vitroand in mice (30 to 60 mg/kg/d s.c.)in vivoby inducing cell cycle arrest at g₀and apoptosis. Reduced frequency of sphere-forming cells is observed among surviving cells (by 1.7- to 2.2-fold) upon PTC-209 removal post a 4-day 0.1 µM drug treatment period in primary colon cancer cultures, indicating a greater impact of drug treatment on self-renewing cancer-initiating cells (CICs; cancer stem cells). Likewise, surviving colon cancer cells from tumor-bearing mice at the end of drug treatment are shown to contain reduced population of tumor-initiating cells when xenografted into secondary recipient mice.A cell-permeable imidazopyrimidinyl-thiazolamine compound that effectively downregulates cellular BMI-1 protein level both in culturesin vitro(IC₅₀= 0.5 µM/48 H/HT1080 and <0.37 µM/HCT116/overnight) and in micein vivo(60 mg/kg/d via s.c.) by inhibiting BMI-1 transcription via a yet unidentified mechanism, thereby reducing BMI-1-dependent RING1A E3 ligase activity and RING1A-mediated H2A ubiquitination (uH2A)/epigenetic regulations. Shown to exhibit antiproliferation activity against human colon cancer cells both in cultures (IC₅₀<300 nM)in vitroand in mice (30 to 60 mg/kg/d s.c.)in vivovia G0 cell cycle arrest and apoptosis induction with a greater drug impact on self-renewing cancer-initiating cells (CICs; cancer stem cells).

Biochem/Physiol Actions

Cell permeable: yesReversible: no

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

Kreso, A., et Al. 2014.Nat. Med. 20,29.CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany