PIM447 (LGH447)
PIM447 (LGH447)是一种新型的、泛PIM激酶抑制剂，对PIM1、PIM2、PIM3的Ki值分别为6 pM、18 pM、9 pM。它还能抑制 GSK3β, PKN1和PKCτ，但抑制效力较小，IC50在1-5 μM范围间。 PIM447 可诱导凋亡。
PIM447 (LGH447) Chemical Structure
CAS: 1210608-43-7(freebase)
客户使用Selleck的PIM447 (LGH447)发表文献17篇
客户使用该产品的1个实验数据
产品质控
PIM447 (LGH447)相关产品
| 相关靶点 | Pim1 Pim2 Pim3 | 点击展开 |
|---|---|---|
| 相关产品 | SGI-1776 free base AZD1208 SMI-4a CX-6258 HCl Uzansertib (INCB053914) TP-3654 Hispidulin SMI-16a | 点击展开 |
| 相关化合物库 | 激酶抑制剂库 FDA药物库 天然产物库 酪氨酸激酶抑制剂分子库 JAK-STAT信号通路库 | 点击展开 |
相关信号通路图
Pim抑制剂选择性比较
细胞实验数据示例
| 细胞系 | 实验类型 | 给药浓度 | 孵育时间 | 活性描述 | 文献信息 |
|---|---|---|---|---|---|
| KG1 | Function assay | 100 mg/kg | 24 hrs | Unbound plasma concentration in mouse xenografted with human KG1 cells at 100 mg/kg, po after 24 hrs by LC/MS/MS analysis, Cp(f)=0.3μM | 26505898 |
| KG1 | Antitumor assay | 30 mg/kg | 11 days | Antitumor activity against human KG1 cells xenografted in mouse assessed as tumor stasis at 30 mg/kg, po qd measured after 11 days post tumor implantation | 26505898 |
| KG1 | Antitumor assay | 30 to 100 mg/kg | 11 days | Antitumor activity against human KG1 cells xenografted in mouse assessed as tumor regression at 30 to 100 mg/kg, po qd measured after 11 days post tumor implantation in presence of 100 mg/kg Ara-C | 26505898 |
| MOLM16 | Antiproliferative assay | 3 days | Antiproliferative activity against human MOLM16 cells after 3 days by CellTiter-Glo assay, GI50=0.01μM | 26505898 | |
| KG1 | Antiproliferative assay | 3 days | Antiproliferative activity against human KG1 cells after 3 days by CellTiter-Glo assay, GI50=0.01μM | 26505898 | |
| EOL-1 | Antiproliferative assay | 3 days | Antiproliferative activity against human EOL-1 cells after 3 days by CellTiter-Glo assay, GI50=0.01μM | 26505898 | |
| M07e | Antiproliferative assay | 3 days | Antiproliferative activity against human M07e cells after 3 days by CellTiter-Glo assay, GI50=0.05μM | 26505898 | |
| UKE1 | Antiproliferative assay | 3 days | Antiproliferative activity against human UKE1 cells after 3 days by CellTiter-Glo assay, GI50=0.09μM | 26505898 | |
| MV411 | Antiproliferative assay | 3 days | Antiproliferative activity against human MV411 cells after 3 days by CellTiter-Glo assay, GI50=0.13μM | 26505898 | |
| KMS11 | Antiproliferative assay | 72 hrs | Antiproliferative activity against luciferase expressing human KMS11 cells after 72 hrs by Cell-TiterGlo assay, EC50=0.17μM | 26505898 | |
| KMS11 | Function assay | 1 hr | Inhibition of PIM kinase in luciferase expressing human KMS11 cells assessed as inhibition of phosphorylation of S6RP after 1 hr by electrochemiluminescence assay, EC50=0.18μM | 26505898 | |
| CMK | Antiproliferative assay | 3 days | Antiproliferative activity against human CMK cells after 3 days by CellTiter-Glo assay, GI50=0.28μM | 26505898 | |
| SET2 | Antiproliferative assay | 3 days | Antiproliferative activity against human SET2 cells after 3 days by CellTiter-Glo assay, GI50=0.48μM | 26505898 | |
| CMK-11-5 | Antiproliferative assay | 3 days | Antiproliferative activity against human CMK-11-5 cells after 3 days by CellTiter-Glo assay, GI50=1.03μM | 26505898 | |
| MOLM13 | Antiproliferative assay | 3 days | Antiproliferative activity against human MOLM13 cells after 3 days by CellTiter-Glo assay, GI50=1.39μM | 26505898 | |
| HEL 92.1.7 | Antiproliferative assay | 3 days | Antiproliferative activity against human HEL 92.1.7 cells after 3 days by CellTiter-Glo assay, GI50=1.66μM | 26505898 | |
| TF1 | Antiproliferative assay | 3 days | Antiproliferative activity against human TF1 cells after 3 days by CellTiter-Glo assay, GI50=1.96μM | 26505898 | |
| MUTZ8 | Antiproliferative assay | 3 days | Antiproliferative activity against human MUTZ8 cells after 3 days by CellTiter-Glo assay, GI50=1.99μM | 26505898 | |
| OCI-M1 | Antiproliferative assay | 3 days | Antiproliferative activity against human OCI-M1 cells after 3 days by CellTiter-Glo assay, GI50=2.57μM | 26505898 | |
| SKM1 | Antiproliferative assay | 3 days | Antiproliferative activity against human SKM1 cells after 3 days by CellTiter-Glo assay, GI50=2.69μM | 26505898 | |
| OCI-AML3 | Antiproliferative assay | 3 days | Antiproliferative activity against human OCI-AML3 cells after 3 days by CellTiter-Glo assay, GI50=2.92μM | 26505898 | |
| P31/FUJ | Antiproliferative assay | 3 days | Antiproliferative activity against human P31/FUJ cells after 3 days by CellTiter-Glo assay, GI50=5.06μM | 26505898 | |
| MONO-MAC-1 | Antiproliferative assay | 3 days | Antiproliferative activity against human MONO-MAC-1 cells after 3 days by CellTiter-Glo assay, GI50=5.19μM | 26505898 | |
| THP1 | Antiproliferative assay | 3 days | Antiproliferative activity against human THP1 cells after 3 days by CellTiter-Glo assay, GI50=5.31μM | 26505898 | |
| OCI-AML2 | Antiproliferative assay | 3 days | Antiproliferative activity against human OCI-AML2 cells after 3 days by CellTiter-Glo assay, GI50=5.53μM | 26505898 | |
| NB4 | Antiproliferative assay | 3 days | Antiproliferative activity against human NB4 cells after 3 days by CellTiter-Glo assay, GI50=7μM | 26505898 | |
| PL21 | Antiproliferative assay | 3 days | Antiproliferative activity against human PL21 cells after 3 days by CellTiter-Glo assay, GI50=8.56μM | 26505898 | |
| SIG-M5 | Antiproliferative assay | 3 days | Antiproliferative activity against human SIG-M5 cells after 3 days by CellTiter-Glo assay, GI50=8.66μM | 26505898 | |
| NOMO1 | Antiproliferative assay | 3 days | Antiproliferative activity against human NOMO1 cells after 3 days by CellTiter-Glo assay, GI50=10μM | 26505898 | |
| F-36P | Antiproliferative assay | 3 days | Antiproliferative activity against human F-36P cells after 3 days by CellTiter-Glo assay, GI50=10μM | 26505898 | |
| OCI-AML5 | Antiproliferative assay | 3 days | Antiproliferative activity against human OCI-AML5 cells after 3 days by CellTiter-Glo assay, GI50=10μM | 26505898 | |
| 点击查看更多细胞系数据 | |||||
生物活性
| 产品描述 | PIM447 (LGH447)是一种新型的、泛PIM激酶抑制剂，对PIM1、PIM2、PIM3的Ki值分别为6 pM、18 pM、9 pM。它还能抑制 GSK3β, PKN1和PKCτ，但抑制效力较小，IC50在1-5 μM范围间。 PIM447 可诱导凋亡。 | ||||||
|---|---|---|---|---|---|---|---|
| 靶点 |
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| 体外研究(In Vitro) | ||||
| 体外研究活性 | 通过对68种不同蛋白激酶（包括PIM2）以及9种脂质激酶的生化检测发现，PIM447具有高特异性，在其中，只有PIM2能被PIM447显著地抑制，IC50<0.003 μM。PIM447还能抑制GSK3β, PKN1和PKCτ，但作用效力弱，IC50在1-5 μM之间。而对其他所检测的激酶的IC50值大于9 μM。在接下的细胞实验中，当PIM447的浓度高达20 μM时，其对GSK3β没有活性[1]。PIM447对骨髓瘤细胞来说具有细胞毒性，能够破坏其细胞周期并诱引起Bad(Ser112)和c-Myc水平的减低，从而诱导凋亡、抑制mTORC1通路。PIM447在体外还能够抑制破骨细胞的形成和再吸收、下调参与这些过程的关键分子、破坏F-actin环、增强成骨细胞活性及矿化[2]。 | |||
|---|---|---|---|---|
| 细胞实验 | 细胞系 | KG-1细胞 | ||
| 浓度 | 0.05, 0.5 和 5 μM | |||
| 孵育时间 | 2 h | |||
| 方法 | 用一定浓度的PIM447处理KG-1细胞2小时后，将细胞置于RIPA buffer中进行裂解。用BCA法检测蛋白质浓度，将50 μg溶解产物用SDS-PAGE法进行分离、电泳。然后将蛋白转移至0.2 μm硝酸纤维膜（转膜），WB检测pS6RP/总S6RP的表达量。 |
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| 体内研究(In Vivo) | ||
| 体内研究活性 | 在各个物种中，PIM447的清除率都比较低，在小鼠、大鼠和犬类中，其清除率分别为20, 28和8 mL/min/kg。分布容积大，在小鼠、大鼠和犬类中Vss分别为5.3、6.4、3.6 L/kg。PIM447还具有高的口服生物利用度，在小鼠、大鼠和犬类中分别为84%、70%和71%。在人体血浆中，PIM447很稳定，给药后3小时还存有90%，血浆蛋白结合率为95%。PIM447在体内具有调节靶标（pS6RP）作用，在KG-1 AML小鼠移植瘤模型中具有单药抗肿瘤活性，其类药性属性使其非常适合用于开发[1]。在散播性人类骨髓瘤小鼠模型中，PIM447能够显著地减少肿瘤负荷、阻止肿瘤相关的骨质疏松[2]。 | |
|---|---|---|
| 动物实验 | Animal Models | KG-1 AML xenograft mouse model |
| Dosages | 30 或 100 mg/kg | |
| Administration | 口服 | |
| NCT Number | Recruitment | Conditions | Sponsor/Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| NCT02160951 | Completed | Multiple Myeloma |
Novartis Pharmaceuticals|Novartis |
September 2014 | Phase 1 |
| NCT02078609 | Completed | AML and High Risk MDS |
Novartis Pharmaceuticals|Novartis |
March 20 2014 | Phase 1 |
| NCT01456689 | Completed | Multiple Myeloma |
Novartis Pharmaceuticals|Novartis |
April 25 2012 | Phase 1 |
化学信息&溶解度
| 分子量 | 476.92 | 分子式 | C24H23F3N4O.HCl |
| CAS号 | 1210608-43-7(freebase) | SDF | -- |
| Smiles | CC1CC(CC(C1)N)C2=C(C=NC=C2)NC(=O)C3=NC(=C(C=C3)F)C4=C(C=CC=C4F)F | ||
| 储存条件(自收到货起) | |||
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体外溶解度 |
DMSO : 95 mg/mL ( (199.19 mM)； DMSO吸湿会降低化合物溶解度，请使用新开封DMSO) Ethanol : 95 mg/mL Water : Insoluble |
摩尔浓度计算器 |
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体内溶解度 现配现用，请按从左到右的顺序依次添加，澄清后再加入下一溶剂 |
动物体内配方计算器 | ||||
实验计算
动物体内配方计算器（澄清溶液）
第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量）
第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系Selleck为您提供正确的澄清溶液配方）
计算结果：
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于μL DMSO溶液（母液浓度mg/mL，注：如该浓度超过该批次药物DMSO溶解度，请先联系Selleck）；
体内配方配制方法：取μL DMSO母液，加入μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入μL ddH2O，混匀澄清。
体内配方配制方法：取μL DMSO母液，加入μL Corn oil，混匀澄清。
注意：1. 首先保证母液是澄清的；
2.一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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