2. Cell Cycle/DNA Damage Apoptosis JAK/STAT Signaling Stem Cell/Wnt Protein Tyrosine Kinase/RTK Epigenetics PI3K/Akt/mTOR
  3. Deubiquitinase Apoptosis STAT JAK Akt PI3K
  4. WCY-8-67

WCY-8-67 是一种具有口服活性的选择性 USP5 抑制剂，其 IC50 值为 1.33 μM。WCY-8-67 在体外诱导凋亡 (apoptosis) 并抑制 JAK/STAT3 和 PI3K/AKT 信号通路。WCY-8-67 抑制 AE 阳性 AML 细胞的增殖，诱导 AML 细胞的 G1 期阻滞和分化。WCY-8-67 在小鼠中显示出强效的抗白血病疗效。WCY-8-67 可用于急性髓系白血病研究。

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WCY-8-67

WCY-8-67 Chemical Structure

CAS No. : 3052618-54-6

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WCY-8-67 相关抗体

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  • 生物活性

  • 纯度 & 产品资料

  • 参考文献

生物活性

WCY-8-67 is an orally active and selective USP5 inhibitor, with an IC50 value of 1.33 μM. WCY-8-67 induces apoptosis and suppresses JAK/STAT3 and PI3K/AKT signaling pathways in vitro. WCY-8-67 inhibits proliferation of AE-positive AML cells, induces G1 phase arrest and differentiation of AML cells. WCY-8-67 demonstrates potent anti-leukemic efficacy in mice. WCY-8-67 can be used for the study of acute myeloid leukemia[1].

IC50 & Target[1]

USP5

1.33 μM (IC50)

体外研究
(In Vitro)

WCY-8-67 (0.5-2 μM, 24 h) 以剂量依赖方式降低 Kasumi-1 和 Skno-1 细胞中的 AML1-ETO (AE) 蛋白丰度[1]。
WCY-8-67 (0.5-2 μM, 24 h) 抑制 AE 阳性 AML 细胞的增殖（Kasumi-1: IC50 = 1.75 μM; Skno-1: IC50 = 0.99 μM; U937-AE: IC50 = 1.20 μM），但对 AE 阴性 AML 细胞（MV-4-11, MOLM-13, HL-60）影响甚微[1]。
WCY-8-67 (0.5-7.5 μM, 24-48 h) 在 Kasumi-1 和 Skno-1 细胞中诱导凋亡和 G1 期细胞周期阻滞[1]。
WCY-8-67 (0.5-2 μM, 7 days) 在琼脂糖菌落实验中减少 Kasumi-1 和 Skno-1 细胞的菌落形成，降低恶性克隆数量[1]。
WCY-8-67 (0.5-2 μM, 24 h) 减少 Kasumi-1 和 Skno-1 细胞中的 CD34+CD38- 白血病干细胞 (LSC) 群体，并增加 CD11b+ 分化细胞群体[1]。
WCY-8-67 (0-2.5 μM, 24 h) 在 Kasumi-1 和 Skno-1 细胞中抑制 JAK/STAT3 和 PI3K/AKT 信号通路[1]。

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

WCY-8-67 相关抗体:

Apoptosis Analysis[1]

Cell Line: Kasumi-1 and Skno-1 cells
Concentration: 0, 1.25, 5, 7.5 μM
Incubation Time: 48 h
Result: Downregulated MDM2 and upregulated p53.
Promoted cleavage of PARP1 and activation of caspase-3.
Reduced anti-apoptotic proteins Bcl-2 and Mcl-1.
体内研究
(In Vivo)

WCY-8-67 (20-40 mg/kg，口服，每日一次，12 天) 在 Skno-1 皮下异种移植模型中显示出强效的抗肿瘤活性[1]。
WCY-8-67 (40 mg/kg，口服，每日一次，42 天) 在 Kasumi-1-luciferase-GFP 原位异种移植模型中减少肿瘤负荷并延长生存期[1]。
WCY-8-67 (20 mg/kg，腹腔注射，每日一次，14 天) 在 t(8;21) AML 异种移植 (PDX) 模型中延长生存期并减轻脾脏重量[1]。

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: Skno-1 cells (1 × 107) were subcutaneously implanted into the flanks of 6-week-old female NU/NU mice[1]
Dosage: 20, 40 mg/kg
Administration: p.o., once daily, 12 days
Result: Reduced tumor weight and volume.
Showed no significant changes in body weight.
Animal Model: Kasumi-1 cells expressing luciferase-GFP (2 × 106) were intravenously injected into the tail veins of the 6-week-old NOG mice[1]
Dosage: 40 mg/kg
Administration: p.o., once daily, 42 days
Result: Decreasedspleen weight and hCD45+ leukemic cell percentage in bone marrow, spleen, and peripheral blood.
Reduced tumor burden and extends survival.
Animal Model: Primary t(8;21) AML cells were intravenously injected into the tail veins of the 6-week-old NOG mice[1]
Dosage: 20 mg/kg
Administration: i.p., once daily, 14 days
Result: Decreased hCD45+ cell infiltration in bone marrow, spleen, and peripheral blood.
Prolonged survival and reduces spleen weight.
分子量

449.57

Formula

C25H32FN7
CAS 号
运输条件

Room temperature in continental US; may vary elsewhere.
储存方式

Please store the product under the recommended conditions in the Certificate of Analysis.
纯度 & 产品资料
参考文献

WCY-8-67 相关分类

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  • Do most proteins show cross-species activity?

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Keywords:

WCY-8-673052618-54-6DeubiquitinaseApoptosisSTATJAKAktPI3KDUBsJanus kinasePKBProtein kinase BPhosphoinositide 3-kinaseJAK/STAT3PI3K/AKTAML cellsacute myeloid leukemiaInhibitorinhibitorinhibit

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