SI-2 Property

Boiling point:

459.9±37.0 °C(Predicted)

Density 

1.22±0.1 g/cm3(Predicted)

storage temp. 

2-8°C

solubility 

Soluble in DMSO (up to 20 mg/ml).

pka

11.05±0.70(Predicted)

form 

solid

color 

Pale orange

Stability:

Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20° for up to 1 month.

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H315Causes skin irritation

H319Causes serious eye irritation

Precautionary statements

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

SI-2 Chemical Properties,Usage,Production

Description

SI-2 (380537-35-9) is a potent inhibitor of steroid receptor coactivator-3 (SRC-3).1?It blocks MDA-MB-468 cell growth with an IC50?= 3.4 nM without effecting normal cells.1?It significantly inhibited breast cancer cell growth in an orthotopic MDA-MD-468 mouse model. Treatment of MCF-7 or triple negative MDA-MB-231 cells with SI-2 resulted in inhibition of proliferation and breast cancer stem cell (CSC) tumorsphere formation.2?CSC markers CD44+/CD24-/1o?and aldehyde dehydrogenase (ALDH) were also reduced indicating that SI-2 can selectively interfere with the TIC/CSC state in breast cancer cells.2,3

Uses

SI-2 is an inhibitor of steroid receptor coactivator-3 (SRC-3). Induces cell death in verious breast cancer cells.

Biochem/physiol Actions

SI-2 targets the receptor-interacting domain (RID) of steroid receptor coactivators (SRCs) and suppresses cellular transcriptional activity (Effec. conc. >/= 5 nM in cell-based SRC-1, SRC-2, and SRC-3 reporter assays) by downregulating SRCs protein, but not transcript level (Effec. conc. >/= 12.5 nM against SRC-3, >/= 25 nM against SRC-1 and SCR-2 in MDA-MB-468 culture). SI-2 is cytotoxic to breast cancer cultures (IC50?= 1.5 nM/BT-474, 3.4 nM/MDA-MB-468, 22 nM/MCF-7), but not to normal hepatocytes even at 500 nM concentration. SI-2 is reported to be orally available in mice and, when administered intraperitoneally (2 mg/kg b.i.d.), effectively suppress MDA-MB-468-derived tumor expansion in mice?in vivowith good pharmacokinetics (Cmax?= 30 μM,?tmax?= 0.25 h,?t1/2?= 1.0 h; 20 mg/kg i.p.) and no apparent adverse effects to the animals.

References

1) Song?et al.?(2016),?Development of potent small-molecule inhibitors to drug the undruggable steroid receptor coactivator-3; Proc. Natl. Acad. Sci. USA?113?4970 2) Rohira?et al.?(2017),?Targeting SRC Coactivators Blocks the Tumor-Initiating Capacity of Cancer Stem-like Cells; Cancer Res.?77?4293 3) Truong?et al.?(2018),?Cancer Stem Cell Phenotypes in ER+ Breast Cancer Models are Promoted by PELP/AIB1 Complexes; Mol. Cancer Res.?16?707