Vismodegib (GDC-0449), 平滑肌同源物抑制剂

Hedgehog Selective Inhibitors

Moligand™

10mM in DMSO

CAS编号: 879085-55-9(DMSO)
分子式: C₁₉H₁₄Cl₂N₂O₃S
分子量: 421.3

有货

库存信息

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货号 (SKU)	包装规格	是否现货	价格	数量
V408303-1ml	1ml	现货

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基本描述

别名	维斯莫德吉 (GDC-0449)
英文别名	2-chloro-N-(4-chloro-3-(pyridin-2-yl)phenyl)-4-(methylsulfonyl)benzamide
规格或纯度	Moligand™, 10mM in DMSO
英文名称	Vismodegib (GDC-0449)
生化机理	Vismodegib（GDC-0449）是一种强效、新型和特异性刺猬抑制剂，IC50 为 3 nM，在无细胞试验中还能抑制 P-gp，IC50 为 3.0 μM。
储存温度	-80℃储存
运输条件	超低温冰袋运输
作用类型	抑制剂
作用机制	平滑肌同源物抑制剂
产品介绍	Vismodegib (GDC-0449)是一种有效的，新型的，特异性的hedgehog抑制剂，IC50为3 nM。GDC-0449也抑制P-gp作用，IC50为3.0μM。A potent hedgehog (Hh) signaling pathway inhibitor. Information Vismodegib (GDC-0449) is a potent, novel and specifichedgehoginhibitor withIC50of 3 nM and also inhibits P-gp withIC50of 3.0 μM in a cell-free assay. In vitro GDC-0449 targets the Hedgehog signaling pathway, blocking the activities of the Hedgehog-ligand cell surface receptors PTCH and/or SMO and suppressing Hedgehog signaling. GDC-0449 prevents multiple ATP-binding cassette (ABC) transporters. GDC-0449 also blocks ABCG2, Pgp, and MRP1-important ABC transporters associated with MDR. GDC-0449 is a potent inhibitor of ABC transporters, ABCG2/BCRP and ABCB1/Pgp, and is a mild inhibitor of ABCC1/MRP1. In ABCG2-overexpressing HEK293 cells, GDC-0449 increases retention of the fluorescent ABCG2 substrate BODIPY-prazosin and resensitizes these cells to mitoxantrone. In Madin-Darby canine kidney II cells engineered to overexpress Pgp or MRP1, GDC-0449 increases the retention of calcein-AM and resensitizes them to colchicine. GDC-0449 also resensitizes human non-small cell lung carcinoma cells NCI-H460/par and NCI-H460/MX20, which overexpress ABCG2 in response to mitoxantrone, to mitoxantrone, and to topotecan or SN-38. The IC50 values of GDC-0449 for prevention of ABCG2 and Pgp are about 1.4 μM and 3.0 μM, respectively. GDC-0449 alters intracellular Ca²⁺ homeostasis and inhibits cell growth in cisplatin-resistant lung cancer cells. In vivo GDC-0449 has been used to treat medulloblastoma in animal models. GDC-0449 prevents the growth of primary pancreatic xenografts without non-specifically inhibiting pancreatic cell proliferation. Oral dosing of GDC-0449 causes tumor regressions in the Ptch(+/-) allograft model of medulloblastoma at doses ≥25 mg/kg and tumor growth inhibition at doses up to 92 mg/kg dosed twice daily in two ligand-dependent colorectal cancer models, D5123, and 1040830. Analysis of Hh pathway activity and PK/PD modeling reveals that GDC-0449 inhibits Gli1 with a similar IC50 in both the medulloblastoma and D5123 models (0.165 μM and 0.267 μM, respectively). Pathway modulation is linked to efficacy using an integrated PK/PD model revealing a steep relationship where > 50% of the activity of GDC-0449 is associated with >80% repression of the Hh pathway. Cell Data cell lines：H2AX cells Concentrations：20 μM Incubation Time：2 hours Powder Purity:≥99%