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- 2x SYBR Green qPCR Master Mix
- 2x SYBR Green qPCR Master Mix(Low ROX)
- 2x SYBR Green qPCR Master Mix(High ROX)
- 蛋白實驗
- Protein A/G免疫沉淀磁珠
- Anti-DYKDDDDK Tag免疫磁珠
- Anti-DYKDDDDK Tag親和凝膠
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- Anti-HA免疫磁珠
- 磁力架
- Poly DYKDDDDK Tag多肽
- 細(xì)胞核與細(xì)胞漿蛋白抽提試劑盒
- 免疫磁珠
- 蛋白酶抑制劑Cocktail
- 蛋白酶抑制劑Cocktail(DMSO儲液)
- 磷酸酶抑制劑Cocktail
- 細(xì)胞實驗
- Cell Counting Kit-8 (CCK-8)
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PIM447 (LGH447) Hydrochloride
PIM447 (LGH447) Hydrochloride是一種新型的、泛PIM激酶抑制劑，對PIM1、PIM2、PIM3的Ki值分別為6 pM、18 pM、9 pM。它還能抑制 GSK3β, PKN1和PKCτ，但抑制效力較小，IC50在1-5 μM范圍間。 PIM447 可誘導(dǎo)凋亡。
PIM447 (LGH447) Hydrochloride Chemical Structure
CAS: 1210416-52-6
產(chǎn)品質(zhì)控
批次：
純度：
99.06%
99.06
PIM447 (LGH447) Hydrochloride相關(guān)產(chǎn)品
| 相關(guān)靶點 | Pim1 Pim2 Pim3 | 點擊展開 |
|---|---|---|
| 相關(guān)產(chǎn)品 | SGI-1776 free base AZD1208 SMI-4a CX-6258 HCl Uzansertib (INCB053914) TP-3654 Hispidulin SMI-16a | 點擊展開 |
| 相關(guān)化合物庫 | 激酶抑制劑庫 FDA藥物庫 天然產(chǎn)物庫 酪氨酸激酶抑制劑分子庫 JAK-STAT信號通路庫 | 點擊展開 |
相關(guān)信號通路圖
細(xì)胞實驗數(shù)據(jù)示例
| 細(xì)胞系 | 實驗類型 | 給藥濃度 | 孵育時間 | 活性描述 | 文獻(xiàn)信息(PMID) |
|---|---|---|---|---|---|
| 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 | |
| 點擊查看更多細(xì)胞系數(shù)據(jù) | |||||
生物活性
| 產(chǎn)品描述 | PIM447 (LGH447) Hydrochloride是一種新型的、泛PIM激酶抑制劑，對PIM1、PIM2、PIM3的Ki值分別為6 pM、18 pM、9 pM。它還能抑制 GSK3β, PKN1和PKCτ，但抑制效力較小，IC50在1-5 μM范圍間。 PIM447 可誘導(dǎo)凋亡。 | ||||||
|---|---|---|---|---|---|---|---|
| 靶點 |
|
| 體外研究(In Vitro) | ||||
| 體外研究活性 | 通過對68種不同蛋白激酶（包括PIM2）以及9種脂質(zhì)激酶的生化檢測發(fā)現(xiàn)，PIM447具有高特異性，在其中，只有PIM2能被PIM447顯著地抑制，IC50<0.003 μM。PIM447還能抑制GSK3β, PKN1和PKCτ，但作用效力弱，IC50在1-5 μM之間。而對其他所檢測的激酶的IC50值大于9 μM。在接下的細(xì)胞實驗中，當(dāng)PIM447的濃度高達(dá)20 μM時，其對GSK3β沒有活性[1]。PIM447對骨髓瘤細(xì)胞來說具有細(xì)胞毒性，能夠破壞其細(xì)胞周期并誘引起B(yǎng)ad(Ser112)和c-Myc水平的減低，從而誘導(dǎo)凋亡、抑制mTORC1通路。PIM447在體外還能夠抑制破骨細(xì)胞的形成和再吸收、下調(diào)參與這些過程的關(guān)鍵分子、破壞F-actin環(huán)、增強(qiáng)成骨細(xì)胞活性及礦化[2]。 | |||
|---|---|---|---|---|
| 細(xì)胞實驗 | 細(xì)胞系 | KG-1細(xì)胞 | ||
| 濃度 | 0.05, 0.5 和 5 μM | |||
| 孵育時間 | 2 h | |||
| 方法 | 用一定濃度的PIM447處理KG-1細(xì)胞2小時后，將細(xì)胞置于RIPA buffer中進(jìn)行裂解。用BCA法檢測蛋白質(zhì)濃度，將50 μg溶解產(chǎn)物用SDS-PAGE法進(jìn)行分離、電泳。然后將蛋白轉(zhuǎn)移至0.2 μm硝酸纖維膜（轉(zhuǎn)膜），WB檢測pS6RP/總S6RP的表達(dá)量。 |
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| 體內(nèi)研究(In Vivo) | ||
| 體內(nèi)研究活性 | 在各個物種中，PIM447的清除率都比較低，在小鼠、大鼠和犬類中，其清除率分別為20, 28和8 mL/min/kg。分布容積大，在小鼠、大鼠和犬類中Vss分別為5.3、6.4、3.6 L/kg。PIM447還具有高的口服生物利用度，在小鼠、大鼠和犬類中分別為84%、70%和71%。在人體血漿中，PIM447很穩(wěn)定，給藥后3小時還存有90%，血漿蛋白結(jié)合率為95%。PIM447在體內(nèi)具有調(diào)節(jié)靶標(biāo)（pS6RP）作用，在KG-1 AML小鼠移植瘤模型中具有單藥抗腫瘤活性，其類藥性屬性使其非常適合用于開發(fā)[1]。在散播性人類骨髓瘤小鼠模型中，PIM447能夠顯著地減少腫瘤負(fù)荷、阻止腫瘤相關(guān)的骨質(zhì)疏松[2]。 | |
|---|---|---|
| 動物實驗 | 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 |
|
化學(xué)信息&溶解度
| 分子量 | 476.92 | 分子式 | C24H23F3N4O.HCl |
| CAS號 | 1210416-52-6 | 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 | ||
| 儲存條件(自收到貨起) | |||
|
體外溶解度 |
DMSO : 95 mg/mL ( (199.19 mM) ；DMSO吸濕會降低化合物溶解度，請使用新開封DMSO) Ethanol : 95 mg/mL (199.19 mM) Water : Insoluble |
摩爾濃度計算器 |
|
體內(nèi)溶解配方 現(xiàn)配現(xiàn)用，請按從左到右的順序依次添加，澄清后再加入下一溶劑 |
動物體內(nèi)配方計算器 | |||||
實驗計算
動物體內(nèi)配方計算器（澄清溶液）
第一步：請輸入基本實驗信息（考慮到實驗過程中的損耗，建議多配一只動物的藥量）
mg/kg
g
μL
只
第二步：請輸入動物體內(nèi)配方組成（配方適用于不溶于水的藥物；不同批次藥物配方比例不同，請聯(lián)系Selleck為您提供正確的澄清溶液配方）
% DMSO
%
% Tween 80
% ddH2O
%DMSO
%
計算結(jié)果：
工作液濃度： mg/ml；
DMSO母液配制方法： mg 藥物溶于μL DMSO溶液（母液濃度mg/mL，注：如該濃度超過該批次藥物DMSO溶解度，請先聯(lián)系Selleck）；
體內(nèi)配方配制方法：取μL DMSO母液，加入μL PEG300，混勻澄清后加入μL Tween 80，混勻澄清后加入μL ddH2O，混勻澄清。
體內(nèi)配方配制方法：取μL DMSO母液，加入μL Corn oil，混勻澄清。
注意：1. 首先保證母液是澄清的；
2.一定要按照順序依次將溶劑加入，進(jìn)行下一步操作之前必須保證上一步操作得到的是澄清的溶液，可采用渦旋、超聲或水浴加熱等物理方法助溶。
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