Vamotinib

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

Vamotinib (PF-114) 是一种有效的，选择性具有口服活性的酪氨酸激酶抑制剂。Vamotinib 抑制 BCR/ABL 和 BCR/ABL-T315I 的自磷酸化。Vamotinib 诱导细胞凋亡 (apoptosis)。Vamotinib 显示出抗增殖和抗肿瘤活性。Vamotinib 在耐药性费城染色体阳性 (Ph+) 白血病的研究中具有潜力。Vamotinib 抑制 ABL 系列激酶的 IC50 分别为 0.49 nM (ABL)，0.78 nM (ABLT315I)，9.5 nM (ABLE255K)，2.0 nM (ABLF317I)，7.4 nM (ABLG250E)，1.0 nM (ABLH396P)，2.8 nM (ABLM351T)，12 nM (ABLQ252H) 和 4.1 nM (ABLY253F)。

Vamotinib (PF-114) is a potent, selective and orally active tyrosine kinase inhibitor. Vamotinib inhibits the autophosphorylation of BCR/ABL and BCR/ABL-T315I. Vamotinib induces apoptosis. Vamotinib shows anti-proliferative and anti-tumor activity. Vamotinib has the potential for the research of resistant philadelphia chromosome-positive (Ph+) leukemia. Vamotinib inhibits ABL series kinases with IC50s of 0.49 nM (ABL), 0.78 nM (ABLT315I), 9.5 nM (ABLE255K), 2.0 nM (ABLF317I), 7.4 nM (ABLG250E), 1.0 nM (ABLH396P), 2.8 nM (ABLM351T), 12 nM (ABLQ252H), and 4.1 nM (ABLY253F), respectively. Vamotinib is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.

Vamotinib (0-1 μM) inhibits ABL kinase and its mutants with IC50s of 0.49, 0.78, 1.0 μM for ABL, ABL(T315l), ABL(H396P), respectively.Vamotinib (0-1000 nM) inhibits the autophosphorylation of BCR/ABL and BCR/ABL-T315I in a dose-dependent manner.Vamotinib (0-2000 nM) shows anti-proliferative activity in Ba/F3 cells expressing native BCR/ABL.Vamotinib (0-100 nM) induces apoptosis in Ba/F3 cells expressing BCR/ABL and BCR/ABL-T315I.Vamotinib (0-1000 nM) inhibits the growth of Ph+ patient-derived cell lines in k562, kcl-22, SupB15, Tom-1, BV-173 cells.Vamotinib (0-1000 nM) suppresses growth of Ph+ PD-LTC with nonmutational resistance as well as T315I mutation.Western Blot Analysis Cell Line:Ba/F3 cells Concentration:0, 10, 25, 50, 100, 500, 1000 nM Incubation Time:Result:Inhibited the autophosphorylation of BCR/ABL and BCR/ABL-T315I in a dose-dependent manner and inhibited substrate phosphorylation as shown by the reduced Crkl-phosphorylation and downstream activation of Stat5 by BCR/ABL, as well as by BCR/ABL-T315I.Cell Proliferation Assay Cell Line:Ba/F3 cells Concentration:0, 50, 500, 2000 nM Incubation Time:Result:Potently inhibited proliferation of Ba/F3 cells expressing native BCR/ABL in a dose-dependent manner and shows no effects on empty vector-transduced Ba/F3 cells in the presence of IL-3 (10?ng/ml).Apoptosis Analysis Cell Line:Ba/F3 cells Concentration:0-100 nM Incubation Time:Result:Induced apoptosis in Ba/F3 cells expressing BCR/ABL and BCR/ABL-T315I in a dose dependent manner.

Vamotinib (25, 40 mg/kg; i.g.; daily for 14 consecutive days) shows anti-tumor activity.Vamotinib (50 mg/kg; p.o.; once daily for 20 days) prolongs the survival of mice with both BCR/ABL- and BCR/ABL-T315I-driven CML-like disease.Animal Model:Female BALB/cAnNRj-Foxn1nu mice (K562 nude mouse xenograft model)Dosage:25, 40 mg/kg Administration:Oral gavage; daily for 14 consecutive days Result:Caused a 100% reduction of the mean tumor volume within 4 weeks.Animal Model:8-12 weeks, C57BL/6N mice (CML-like disease mouse model) Dosage:50 mg/kg Administration:P.o.; once daily for 20 days Result:Extended median survival significantly from 28 days to 39.

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Angiogenesis

Bcr-Abl

Bcr-Abl | Apoptosis | Tyrosine Kinases

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1416241-23-0

532.56

C29H27F3N6O

>98% (HPLC)

In Vitro:?DMSO 中的溶解度 : 50 mg/mL (93.89 mM; 超声助溶 )

CN1CCN(Cc2ccc(NC(=O)c3ccc(C)c(c3)C#Cc3nnc4ccccn34)cc2C(F)(F)F)CC1

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(-20℃)

With Ice Pack

≥ 2 years