PF-04929113 Mesylate

• CAT Number: I000613
• CAS Number: 1173111-67-5
• Molecular Formula: C26H34F3N5O7S
• Molecular Weight: 617.64
• Purity: ≥95%
• Target: HSP
• Solubility: 10 mM in DMSO
• Storage: Desiccate at RT
• IC50: 50 nM

PF-04929113 Mesylate (CAT: I000613) is a potent and selective Hsp90 inhibitor with an IC50 value of approximately 50 nM. It belongs to the 6,7-dihydro-indazol-4-one scaffold and converts to its active form, SNX-2122. PF-04929113 exhibits strong inhibitory effects on the stability of Her-2 and induces the up-regulation of Hsp70. In vitro, studies have demonstrated its potent antiproliferative activity against various cancer cell lines, including MCF-7, SW620, K562, SK-MEL-5, and A375, with IC50 values ranging from 16 to 51 nM. In vivo, studies have shown that PF-04929113 inhibits tumor growth, reduces angiogenesis, and prolongs cancer-specific survival. It also exhibits effects on the expression of SP70, Ki67, Akt, and AR, indicating potential mechanisms of tumor progression inhibition. Further research is needed to explore its therapeutic applications and clinical potential.

Reference

[1]. Huang Kenneth H, et al. Discovery of Novel 2-Aminobenzamide Inhibitors of Heat Shock Protein 90 as Potent, Selective and Orally Active Antitumor Agents. Journal of Medicinal Chemistry (2009), 52(14), 4288-4305.

[2]. Rajan A, et al. A phase I study of PF-04929113 (SNX-5422), an orally bioavailable heat shock protein 90 inhibitor, in patients with refractory solid tumor malignancies and lymphomas.Clin Cancer Res. 2011 Nov 1;17(21):6831-9. Epub 2011 Sep 9.

Abstract

[3]. Lamoureux F, et al. Clusterin inhibition using OGX-011 synergistically enhances Hsp90 inhibitor activity by suppressing the heat shock response in castrate-resistant prostate cancer.Cancer Res. 2011 Sep 1;71(17):5838-49. Epub 2011 Jul 7.

[4]. Lamoureux F, et al. A novel HSP90 inhibitor delays castrate-resistant prostate cancer without altering serum PSA levels and inhibits osteoclastogenesis.Clin Cancer Res. 2011 Apr 15;17(8):2301-13. Epub 2011 Feb 24.

[5]. Jain L, et al.Determination of PF-04928473 in human plasma using liquid chromatography with tandem mass spectrometry.J Chromatogr B Analyt Technol Biomed Life Sci. 2010 Nov 15;878(30):3187-92. Epub 2010 Sep 29.