BiochemProbe — Life Science Research Reagents

Inolitazone free base

Inolitazone a novel high-affinity PPARγ agonist that is dependent upon PPARγ for its biological activity with IC50 of 0.8 nM for growth inhibition.

For research use only. Not for human or veterinary use.

Target PPAR
Research area Cancer
Purity >98% Stock Inquire

Inolitazone structure

CAS No.: 223132-37-4

Download structure (.mol)

Pack sizes & pricing

Size Price SKU Stock
50 mg USD 440.00 BP-00022-50mg In stock Get quote
100 mg USD 700.00 BP-00022-100mg In stock Get quote
250 mg USD 1,400.00 BP-00022-250mg In stock Get quote
500 mg USD 2,250.00 BP-00022-500mg In stock Get quote
1 g USD 3,600.00 BP-00022-1g In stock Get quote
2 g Inquire BP-00022-2g In stock Inquire
3 g Inquire BP-00022-3g In stock Inquire

Need another size or custom synthesis? Request a quote.

Description

Inolitazone a novel high-affinity PPARγ agonist that is dependent upon PPARγ for its biological activity with IC50 of 0.8 nM for growth inhibition.

Biological activity

In Vitro Inolitazone (RS5444) upregulates the cell cycle kinase inhibitor, p21 WAF1/CIP1. Silencing p21 WAF1/CIP1 rendered cells insensitive to Inolitazone. A 10 nM dose of Inolitazone activates PPARγ:RXRα-dependent transcription as demonstrated in a transient transfection assay utilizing a PPRE response element fused to a luciferase reporter gene (PPRE3-tk-luc). DRO cells are treated in culture with Inolitazone, Rosiglitazone, or Troglitazone at the indicated concentrations. DRO cells are transiently transfected with PPRE3-tk-luc to examine effective concentrations at which EC50 occurs. The EC50s are 1 nM (Inolitazone), 65 nM (Rosiglitazone) and 631 nM (Troglitazone). Similarly, the calculated inhibitory concentration at IC50 is 0.8 nM for Inolitazone, 75 nM for Rosiglitazone, and 1412 nM for Troglitazone. Inolitazone specifically activates PPARγ, but not PPARα or PPARδ. Exposure of 10 nM Inolitazone following transient transfection with the appropriate PPAR isoform (γ, α, or δ) and PPAR response element linked to a luciferase reporter in RIE rat small intestinal cell line, which does not express PPARs, yields increased luciferase activity only in the presence of PPARγ and PPRE3-tk-luc[1]. DRO cells are growth inhibited by 10 nM Inolitazone (RS5444) through a PPARγ-dependent mechanism. In Vivo Inolitazone (RS5444) plus Paclitaxel demonstrate additive antiproliferative activity in cell culture and minimal ATC tumor growth. When Inolitazone is administered in the diet to athymic nude mice prior to DRO tumor cell implantation, tumor growth is inhibited in a dose responsive fashion. At the highest dose, 0.025% Inolitazone inhibits growth on day 32 by 94.4% as compared to that of control. In this treatment group, five of 10 animals do not develop demonstrable tumors. In the 0.0025% treatment group, tumor growth is inhibited by 62.3% compared to that of control on day 32 while the 0.00025% dose demonstrated no growth inhibitory activity as compared to control. Tumors is nest allowed to establish in the mouse and began 0.025% Inolitazone treatment of mice 1 week after DRO or ARO tumor cell implantation. Inolitazone treated animals demonstrate tumor growth inhibition of 68.9% in DRO tumors and 48.3% in ARO tumors as compared to that of their respective controls on day 35.

Identifiers

SMILES
O=C1SC(C(=O)N1)CC2=CC=C(OCC3=NC=4C=CC(OC=5C=C(C(N)=C(C5)C)C)=CC4N3C)C=C2
InChIKey
JCYNMRJCUYVDBC-UHFFFAOYSA-N

Specifications

MW (average)
502.5850
Formula
C27H26N4O4S
CAS No.
223132-37-4
Physical state
Solid
Color
White to off-white
Shipping
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage
Please store the product under the recommended conditions in the Certificate of Analysis.

References

[1]. Copland JA, et al. Novel high-affinity PPARgamma agonist alone and in combination with paclitaxel inhibits human anaplastic thyroid carcinoma tumor growth via p21WAF1/CIP1. Oncogene. 2006 Apr 13;25(16):2304-17.
[2]. Marlow LA, et al. Reactivation of suppressed RhoB is a critical step for the inhibition of anaplastic thyroid cancer growth. Cancer Res. 2009 Feb 15;69(4):1536-44.

Same target

Search PPAR

Same research area

Search Cancer