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| 化学名: | ベムラフェニブ | | 英語化学名: | PLX4032 | | 别名: | N-(3-(5-(4-Chlorophenyl)-1H-pyrrolo[2,3-B]pyridine-3-carbonyl)-2,4-difluorophenyl)propane-1-sulfonaMide;PLX4032 (VeMurafenib);PLX4032, RG7204, ZELBORAF, RO5185426;R7204;N-(3-(5-(4-Chlorophenyl)-1H-pyrrolo[2,3-B]pyridine-3-carbonyl)-2,4-difluorophenyl)propane-1-sulfonaM;PLX4032, R7204, RG7204, RO5185426;VeMurafenib (PLX4032, RG7204);N-[3-[[5-(4-Chlorophenyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]carbonyl]-2,4-difluorophenyl]-1-propanesulfonamide Vemurafenib PLX 4032 | | CAS番号: | 918504-65-1 | | 分子式: | C23H18ClF2N3O3S | | 分子量: | 489.92 | | EINECS: | | | カテゴリ情報: | API;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals;Protein Kinase Inhibitors and Activators;Sulfur & Selenium Compounds;Inhibitor;RG7204;Antineoplastic;MAPK;Inhibitors;Aromatics | | Mol File: | 918504-65-1.mol |  |
| 比重(密度) | 1.46 | | 貯蔵温度 | -20°C | | 溶解性 | Soluble in DMSO (up to 100 mg/ml) | | 外見 | White powder. | | 酸解離定数(Pka) | 6.26±0.10(Predicted) | | 色 | White or off-white | | 安定性： | Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months. | | CAS データベース | 918504-65-1 |
| | ベムラフェニブ Usage And Synthesis |
| 効能 | 抗悪性腫瘍薬, BRAFキナーゼ阻害薬 | | 商品名 | ゼルボラフ (中外製薬) | | 説明 | In August 2011, the United States FDA approved vemurafenib (PLX-
4032, RO-5185426) for the treatment of patients with metastatic melanoma
with the BRAFV600E mutation. Vemurafenib has been developed as a
targeted therapy for patients with the BRAF gene mutation since oncogenic
B-raf signaling is implicated in approximately 50% of melanomas. Vemurafenib was identified based on an initial high-throughput screen followed by the extensive use of structure-based drug design. Vemurafenib is a potent inhibitor of B-RafV600E kinase (IC50=13 nM) compared to its potency against wildtype B-raf (IC50=160 nM) and is fairly selective versus a panel of 200
kinases. It does inhibit other kinases (RAF1, SRMS, ACK1,
MAP4K5, and FGR) and mutant B-raf kinases (BRAFV600K,
BRAFV600D, and BRAFV600R) with enzyme IC50's of <100 nM. | | 化学的特性 | Off-White Solid | | Originator | Plexxikon (United States) | | 使用 | PLX4032 is an orally bioavailable, ATP-competitive inhibitor of mutant V600E and wild type B-Raf kinases (IC50s = 31 and 100 nM, respectively). It inhibits cell proliferation in a variety of cell lines expressing B-Raf V600E and synergizes strongly with taxol, vinblastine, and oxaliplatin in inhibiting the proliferation of B-RafV600E transformed cancer cells. PLX4032 is effective against the growth of tumors bearing the B-Raf V600E mutation.[Cayman Chemical] | | 使用 | Vemurafenib (PLX4032, RG7204) is a novel and potent inhibitor of B-RafV600E with IC50 of 31 nM | | 使用 | Vemurafenib selective BRAFV600E kinase inhibitor; an antitumor agent. Vemurafenib functions by inhibiting the proliferation and mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase and ERK phosphorylation in a panel of tumor cell lines, including melanoma cell lines expressing BRAFV600E or other mutant BRAF proteins altered at codon 600. | | 定義 | ChEBI: A pyrrolopyridine that is 1H-pyrrolo[2,3-b]pyridine which is substituted at position 5 by a p-chlorophenyl group and at positions 3 by a 3-amino-2,6-difluorobenzoyl group, the amino group of which has undergone
ormal condensation with propane-1-sulfonic acid to give the corresponding sulfonamide. An inhibitor of BRAF and other kinases. | | brand name | Zelboraf | | 生物活性 | Vemurafenib (PLX4032, RG7204, RO5185426) is a novel and potent inhibitor of B-RafV600E with IC50 of 31 nM in cell-free assay. 10-fold selective for B-RafV600E over wild-type B-Raf in enzymatic assays and the cellular selectivity can exceed 100-fold. Vemurafenib (PLX4032, RG7204) induces autophagy. | | in vitro | PLX4032 inhibits B-RAFV600E, C-RAF, as well as wildtype B-RAF, with IC50 of 31 nM, 48 nM and 100 nM, respectively. PLX4032 also inhibits several non-RAF kinases, including ACK1, KHS1, and SRMS, with IC50 of 18 nM to 51 nM. In melanoma cell lines, the inhibitory effect by PLX4032 depends on B-RAF mutational status, because PLX4032 potently inhibits those harboring B-RAF V600 mutants, including V600E, V600D, V600K, and V600R, but not wildtype or other mutants. The IC50 values of PLX4032 on these cells, including MALME-3M, Colo829, Colo38, A375, SK-MEL28, and A2058, ranges from 20 nM to 1 μM. In these cells, PLX4032 (0.1 μM to 30 μM) also inhibits the phosphorylation of both MEK1/2 and ERK1/2. PLX4032 is highly effective in the treatment of melanoma, for its ability of inhibiting B-RAFV600E. However, PLX4032 displays limited effect in colon cancer patients that also carrying B-RAFV600E oncoprotein. The reason for this is that, in colon cancer cells, B-RAFV600E inhibition by PLX4032 results in a rapid feedback EGFR activation, which compensates for the PLX4032-inhibited cell proliferation. | | in vivo | In B-RAFV600E-mutant mice xenograft models, PLX4032 (6 mg/kg–20 mg/kg) inhibits tumor growth. In mice xenograft models of LOX, Colo829, and A375 cells, PLX4032 (12.5 mg/kg–100 mg/kg) inhibits tumor growth and prolongs mice survival. | | target | B-RafV600E | | 貯蔵 | Store at -20°C | | 参考文献 | 1) Khazak?et al. (2007),?Selective Raf inhibition in cancer therapy; Expert Opin. Ther. Targets,?11?1587
2) Tap?et al.?(2010),?Pharmacodynamic characterization of the efficacy signals due to selective BRAF inhibition with PLX4032 in malignant melanoma; Neoplasia,?12?637
3) Lee?et al.?(2010),?PLX4032, a potent inhibitor of the B-Raf V600E oncogene, selectively inhibits V600E-positive melanomas; Pigment Cell Melanoma Res.,?23?820
4) Flaherty?et al.?(2010),?Inhibition of mutated, activated BRAF in metastatic melanoma; N. Engl. J. Med.,?363?809 |
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