PF-04929113 Mesylate
作者：齐岳
发布时间：2023-08-25
08:58:40
点击数：
产品名称：PF-04929113 Mesylate
产品描述：
| 产品描述 | PF-04929113 Mesylate, a prodrug of SNX-2112, is an orally available Hsp90 inhibitor (Kd: 41 nM) and also induces Her-2 degradation (IC50: 37 nM). |
| 靶点活性 | HSP90:41 nM( Kd ), Her-2:37 nM |
| 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. |
| 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. |
| 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. |
| 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. |
| 别名 | PF-04929113 (Mesylate), SNX-5422 Mesylate |
| 分子量 | 617.64 |
| 分子式 | C26H34F3N5O7S |
| CAS No. | 1173111-67-5 |
存储
Powder: -20°C for 3 years | In solvent: -80°C for 2 years
溶解度
DMSO: 27.5 mg/mL (44.52 mM)
( < 1 mg/mL refers to the product slightly soluble or insoluble )
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西安齐岳生物科技有限公司是集化学科研和定制与一体的高科技化学公司。业务范围包括化学试剂和产品的研发、生产、销售等。涉及产品为通用试剂的分销、非通用试剂的定制与研发，涵盖生物科技、化学品、中间体和化工材料等领域。
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