Tyrphostin AG 879

Description

Description

Tyrphostin AG 879 potently inhibits HER2/ErbB2 with IC50 of 1 μM, 100- and 500-fold higher selective to ErbB2 than PDGFR and EGFR.

In vitro

AG879 inhibits growth of FET6αS26X cells in a concentration-dependent manner. ^[1] AG879(10 nM) blocks the activation of PAK1 and suppresses RAS-induced malignant transformation of NIH 3T3 cells. AG879(<1 μM) inhibits the Tyr-phosphorylation of ERK and its association with PAK1 in v-Ha-RAS-transformed NIH 3T3 fibroblasts. ^[2] AG 879 dose-dependently reduce MCF-7 cell numbers and show already a significant effect at 0.4 mM through inhibiting DNA synthesis and mitotic. AG 879(<20 μM) inhibits activation of ERK-1/2 in MCF-7 cell. AG 879(5 μM) decreases expression of Hsp90 client proteins RAF-1 and HER-2. ^[3] AG879(20 μM) dramatically decreases proliferation with a variable increase in apoptosis in Cell lines from human leiomyosarcoma (HTB-114, HTB-115, HTB-88), rhabdomyosarcoma (HTB-82, TE-671), prostatic adenocarcinoma (PC-3), acute promyelocytic leukemia (HL-60) and histiocytic lymphoma (U-937). ^[4]

AG879(2 mg) induces a decrease in cancer growth in athymic NOD/SCID mice grafted with HTB-114 or HL-60.^[4] AG 879(20 mg/kg) treatment keeps 50% of mice absolutely free of RAS-induced sarcomas, and dramatically reduces the size of the growing sarcomas in the nude mice carrying v-Ha-RAS transformed NIH 3T3 cells. ^[5]

Tyrphostin AG 879

Catalog No.S2816

Tyrphostin AG 879 potently inhibits HER2/ErbB2 with IC50 of 1 μM, 100- and 500-fold higher selective to ErbB2 than PDGFR and EGFR.

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Cell lines	MCF-7 cells
Concentrations	20 μM
Incubation Time	46 hours
Method	Cells are grown in 96-well plates containing 100 μL medium per well. Ten microliters of MTT solution (5 mg/ml in PBS) is added to each well and incubation continued for 4 h at 37 °C. Subsequently, 100 μL 10% SDS in 0.01 M HCl is added. After incubation at 37°C overnight, absorption is measured at 550 nm in an ELISA reader using a reference filter of 690 nm.

Animal Models	nude mice carrying v-Ha-RAS transformed NIH 3T3 cells
Dosages	20 mg/kg
Administration	Intraperitoneally administrated on days 3, 5, 7, 10, 12, 14, and 17.
Solubility	1% DMSO/30% polyethylene glycol/1% Tween 80, 30 mg/mL

NCT Number	Recruitment	Conditions	Sponsor /Collaborators	Start Date	Phases
NCT00413699	Recruiting	Arthritis, Rheumatoid	Pfizer	2007-02	Phase 2\|Phase 3
NCT01195662	Completed	Type 2 Diabetes	Bristol-Myers Squibb\|AstraZeneca	2010-10	Phase 3

Solubility (25°C) *	In vitro	DMSO	36 mg/mL (113 mM)
		Water	<1 mg/mL (<1 mM)
		Ethanol	3 mg/mL (9 mM)
	In vivo	1% DMSO/30% polyethylene glycol/1% Tween 80,	30 mg/mL
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.