化合物PF-04929113 Mesylate T4342

Product Introduction
Bioactivity


英文名: PF-04929113 Mesylate

描述: PF-04929113 Mesylate (SNX-5422 Mesylate) 是 SNX-2112 的前药，是一种可口服的 Hsp90 抑制剂 (Kd: 41 nM)，还可诱导 Her-2 降解 (IC50: 37 nM)。

细胞实验: PF-04929113 is dissolved in DMSO.Cell viability is determined by the CCK-8 Assay Kit. Cells (5 × 103/100 μL) in each well on 96-well plates are incubated overnight and treated with the drugs (PF-04929113) for an additional 4 h at 37°C. Absorbance is measured at 450 nm using a spectrophotometer.

激酶实验: Briefly, Hsp90 from porcine spleen extract is isolated by affinity capture on a purine-affinity media. The Hsp90 loaded media is then challenged with test compound (PF-04929113) at a given concentration, ranging from 0.8 to 500 μM, and the amount of Hsp90 liberated at each concentration is determined. The resulting IC50 values are corrected for the ATP ligand concentration and presented as apparent Kd values.

动物实验: PF-04929113 is preformulated in 1% microcrystalline cellulose/0.5% Tween80 in water.Female nude mice are 11 to 12 weeks old and have a body weight range of 18.7?30.5 g on Day 1 of the study. Xenografts are initiated from HT-29 human colon carcinoma tumors maintained by serial transplantation in athymic nude mice. Each test mouse receives a 1 mm3 HT-29 tumor fragment implanted subcutaneously in the right flank, and the growth of tumors is monitored as the average size approached 80?120 mm3. Fourteen days later, designated as Day 1 of the study, individual tumor volumes range from 63 to 126 mm3 and the animals are placed into eight groups, each consisting of 10 mice with group mean tumor volumes of 93.2?93.9 mm3. Micronized PF-04929113 is preformulated in 1% microcrystalline cellulose/0.5% Tween80 in water. The solutions are stored at 4°C during the study and homogenized just prior to dosing. Group 1 vehicle control mice receive D5W (5% dextrose) vehicle by oral gavage beginning on Day 1, every other day for three doses, followed by two days without treatment, for three cycles ((qod × 3)/2 × 3 weeks, a total of nine doses). Groups 2 to 5 animals receive 10 at 5, 10, 25, or 50 mg/kg on the same schedule as vehicle control group ((qod × 3)/2 × 3). Each treatment is administered in a volume of 0.2 mL per 20 g of body weight (10 mL/kg) and is scaled to the body weight of the animal. Tumors are measured twice weekly using calipers.

体外活性: PF-04929113 effectively inhibits Her2 (IC50: 5?±?1 nM) and p-ERK stability in AU565 cells (IC50: 11?±?3 nM) and p-S6 (IC50: 61?±?22 nM) in A375 cells. PF-04929113 also induces Hsp70 in A375 cells (IC50: 13?±?3 nM). PF-04929113 (0.5, 1, 2, 5, and 10 μM) concentration-dependently reduces cell viability. Furthermore, PF-04929113 (1, 3, 5, 7 μM) in combination with equal amounts of HDAC inhibitors (PXD101, SAHA, and TSA) synergistically induces cell death via suppression of PI3K/Akt/mTOR signaling in ATC cells.

体内活性: In HT-29 human colon tumor xenograft model, PF-04929113 (50 mg/kg, p.o.) potently inhibits tumor growth after administration 3 times a week for 3 weeks (qod × 3/2 × 3). PF-04929113 (20/40 mg/kg, p.o.) markedly inhibits multiple myeloma (MM) tumor angiogenesis and growth in mice.

存储条件: Powder: -20°C for 3 years | In solvent: -80°C for 1 year

溶解度: DMSO : 27.5 mg/mL (44.52 mM)


关键字: PF 04929113 Mesylate | PF-04929113 Mesylate | PF04929113 | SNX5422 Mesylate | PF-04929113 | PF 04929113 | PF04929113 Mesylate | SNX 5422 Mesylate

相关产品: Apoptozole | SNX2112 | SMTIN-T140 | HSF1A | VER-50589 | VER-155008 | HSP90-IN-25 | Palmitic acid | VER-49009 | SNX0723

相关库: Drug Repurposing Compound Library | HIF-1 Signaling Pathway Compound Library | Anti-Cancer Compound Library | Anti-Cancer Drug Library | Bioactive Compounds Library Max | Anti-Cancer Clinical Compound Library | Inhibitor Library | Anti-Cancer Active Compound Library | Tyrosine Kinase Inhibitor Library | Apoptosis Compound Library

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