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Ixazomib (MLN2238)
中文名稱：伊沙佐米
Ixazomib (MLN2238)抑制20S proteasome的糜蛋白酶樣蛋白水解(β5)位點，無細胞試驗中IC50和Ki分別為3.4 nM和0.93 nM，也抑制胱天蛋白酶樣(β1)和胰蛋白酶樣(β2)蛋白水解位點，IC50分別為31和3500 nM。Ixazomib (MLN2238)可誘導(dǎo)自噬。Phase 3。
Ixazomib (MLN2238) Chemical Structure
CAS: 1072833-77-2
產(chǎn)品質(zhì)控
批次：
純度：
99.88%
99.88
Ixazomib (MLN2238)相關(guān)產(chǎn)品
| 相關(guān)靶點 | 20S proteasome | 點擊展開 |
|---|---|---|
| 相關(guān)產(chǎn)品 | MG132 Epoxomicin (BU-4061T) Celastrol Oprozomib ONX-0914 (PR-957) Delanzomib VR23 Marizomib (Salinosporamide A) PI-1840 | 點擊展開 |
| 相關(guān)化合物庫 | FDA藥物庫 天然產(chǎn)物庫 已知活性藥物庫-I 蛋白酶抑制劑庫 泛素化化合物庫 | 點擊展開 |
相關(guān)信號通路圖
細胞實驗數(shù)據(jù)示例
| 細胞系 | 實驗類型 | 給藥濃度 | 孵育時間 | 活性描述 | 文獻信息 |
|---|---|---|---|---|---|
| HEK293 | Function assay | 1 hr | Inhibition of NFkappaB in HEK293 cells incubated for 1 hr prior to TNF-alpha challenge measured after 3 hrs by luciferase reporter gene assay relative to control, IC50 = 0.0062 μM. | ChEMBL | |
| Calu6 | Function assay | 1 hr | Inhibition of 26S proteasome beta5 subunit in human Calu6 cells using Suc-LLVY-aminoluciferin as substrate after 1hr by luminescence assay, IC50 = 0.009 μM. | ChEMBL | |
| Calu6 | Cytotoxicity assay | 72 hrs | Cytotoxicity against human Calu6 cells after 72 hrs by luminescence assay, LC50 = 0.014 μM. | ChEMBL | |
| U266B1 | Cytotoxicity assay | 72 hrs | Cytotoxicity against human U266B1 cells assessed as reduction in cell viability after 72 hrs by CellTiter 96 aqueous one solution assay, IC50 = 0.05215 μM. | 29934218 | |
| RPMI8226 | Cytotoxicity assay | 72 hrs | Cytotoxicity against human RPMI8226 cells assessed as reduction in cell viability after 72 hrs by CellTiter 96 aqueous one solution assay, IC50 = 0.05532 μM. | 29934218 | |
| ARH77 | Cytotoxicity assay | 72 hrs | Cytotoxicity against human ARH77 cells assessed as reduction in cell viability after 72 hrs by CellTiter 96 aqueous one solution assay, IC50 = 0.0655 μM. | 29934218 | |
| TC32 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells | 29435139 | ||
| U-2 OS | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for U-2 OS cells | 29435139 | ||
| A673 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells | 29435139 | ||
| DAOY | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells | 29435139 | ||
| Saos-2 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells | 29435139 | ||
| BT-37 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells | 29435139 | ||
| RD | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells | 29435139 | ||
| SK-N-SH | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells | 29435139 | ||
| BT-12 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells | 29435139 | ||
| NB1643 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells | 29435139 | ||
| MG 63 (6-TG R) | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells | 29435139 | ||
| OHS-50 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells | 29435139 | ||
| BT-12 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for BT-12 cells | 29435139 | ||
| DAOY | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for DAOY cells | 29435139 | ||
| fibroblast cells | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for control Hh wild type fibroblast cells | 29435139 | ||
| SK-N-SH | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-SH cells | 29435139 | ||
| Rh41 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells | 29435139 | ||
| A673 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for A673 cells) | 29435139 | ||
| Rh30 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh30 cells | 29435139 | ||
| U-2 OS | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for U-2 OS cells | 29435139 | ||
| Rh41 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh41 cells | 29435139 | ||
| RD | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for RD cells | 29435139 | ||
| SJ-GBM2 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells | 29435139 | ||
| SK-N-MC | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells | 29435139 | ||
| NB-EBc1 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells | 29435139 | ||
| LAN-5 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells | 29435139 | ||
| Rh18 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells | 29435139 | ||
| SJ-GBM2 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SJ-GBM2 cells | 29435139 | ||
| Rh18 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh18 cells | 29435139 | ||
| 點擊查看更多細胞系數(shù)據(jù) | |||||
生物活性
| 產(chǎn)品描述 | Ixazomib (MLN2238)抑制20S proteasome的糜蛋白酶樣蛋白水解(β5)位點，無細胞試驗中IC50和Ki分別為3.4 nM和0.93 nM，也抑制胱天蛋白酶樣(β1)和胰蛋白酶樣(β2)蛋白水解位點，IC50分別為31和3500 nM。Ixazomib (MLN2238)可誘導(dǎo)自噬。Phase 3。 | ||||
|---|---|---|---|---|---|
| 特性 | MLN2238是一流的蛋白酶抑制劑，在臨床前期研究中，提高藥物動力學活性，藥效，及抗癌活性。 | ||||
| 靶點 |
|
| 體外研究(In Vitro) | ||||
| 體外研究活性 | MLN2238是氮端加帽的二肽亮氨酸硼酸，抑制20S 蛋白酶體的糜蛋白酶類(β5)水解位點，IC50為3.4 nM，Ki值為0.93 nM。更高濃度時, MLN2238也抑制20S蛋白酶體的caspase類水解 (β1)位點和胰蛋白酶類水解(β2)位點，IC50分別為31 nM和3.5 μM。MLN2238是蛋白酶體的有效選擇性可逆抑制劑，這種可逆性存在時間依賴性。MLN2238抑制Calu-6細胞，IC50為9.7 nM。MLN2238作用于腫瘤細胞，為蛋白酶體的有效選擇性可逆抑制劑。MLN2238和Bortezomib都為蛋白酶體的可逆抑制劑，都存在時間依賴性，但是MLN2238作用于蛋白酶體的分離半衰期比Bortezomib作用快6倍 (分別為18和110分鐘)。MLN2238從蛋白酶體中分離比Bortezomib快, 與Proteasome-Glo 實驗中蛋白酶體活性更快恢復(fù)一致。 MLN2238 比Bortezomib具有更高的腫瘤藥效。[1] MLN2238是MLN9708的生物活性形式。[2] | |||
|---|---|---|---|---|
| 激酶實驗 | 激酶實驗 | |||
| Calu-6細胞培養(yǎng)在含10%FBS和1%青霉素/鏈霉素的MEM培養(yǎng)基中，1天后，按每孔1×104個細胞加到384孔板上。加入熒光酶素和 Proteasome-Glo檢測試劑，觀察糜蛋白酶類底物Suc-LLVY-aminoluciferin的水解，測定蛋白酶體活性。使用LEADseeker設(shè)備測定熒光值。 | ||||
| 細胞實驗 | 細胞系 | Calu-6 細胞 | ||
| 濃度 | 10nM 左右 | |||
| 孵育時間 | 1小時或30分鐘 | |||
| 方法 | Calu-6細胞培養(yǎng)在含10%FBS和1%青霉素/鏈霉素的MEM培養(yǎng)基中，1天后，按每孔1×104個細胞加到384孔板上。為了測定IC50值，用溶于DMSO (0.5%, v/v)的不同濃度bortezomib或MLN2238在37oC下處理細胞1小時。用于可逆性實驗，用1 μmol/L bortezomib 或MLN2238在37oC下處理細胞30分鐘，然后在培養(yǎng)基中洗三次洗去bortezomib或MLN2238。細胞在37oC下再溫育4小時,然后移除培養(yǎng)基換上新的培養(yǎng)基。 | |||
| 實驗圖片 | 檢測方法 | 檢測指標 | 實驗圖片 | PMID |
| Western blot | PARP / Cleaved PARP / Caspase-3 / Cleaved Caspase-3 Mcl-1 / Bcl-2 p53 / p21 / NOXA / PUMA / pRb / E2F / Cyclin D1 / CDK6 |
|
27687684 | |
| Growth inhibition assay | IC50 |
|
29416618 | |
| 體內(nèi)研究(In Vivo) | ||
| 體內(nèi)研究活性 | MLN2238作用于移植瘤時，比bortezomib產(chǎn)生更強的藥效反應(yīng)。與bortezomib相比，作用于移植瘤時，MLN2238顯示更高的最大值和持久的抑制腫瘤蛋白酶效果。說明用MLN2238處理的腫瘤，藥效反應(yīng)得到明顯提高。MLN2238作用于CWR22移植瘤顯示抗癌活性。與bortezomib 相比，作用于WSU-DLCL2移植瘤模型，MLN2238顯示更強的腫瘤藥效反應(yīng)。[1] 另外，作用于OCI-Ly10和PHTX22L模型，MLN2238比 bortezomib具有更高的藥效和抗癌活性。[2] | |
|---|---|---|
| 動物實驗 | Animal Models | 皮下注射5.0×106個MM.1S細胞的CB-17 SCID鼠 |
| Dosages | 11 mg/kg | |
| Administration | 靜脈注射，每周兩次，持續(xù)三周 | |
| NCT Number | Recruitment | Conditions | Sponsor/Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| NCT00963820 | Completed | Multiple Myeloma |
Millennium Pharmaceuticals Inc.|Takeda |
October 2009 | Phase 1 |
化學信息&溶解度
| 分子量 | 361.03 | 分子式 | C14H19BCl2N2O4 |
| CAS號 | 1072833-77-2 | SDF | Download Ixazomib (MLN2238) SDF |
| Smiles | B(C(CC(C)C)NC(=O)CNC(=O)C1=C(C=CC(=C1)Cl)Cl)(O)O | ||
| 儲存條件(自收到貨起) | |||
|
體外溶解度 |
DMSO : 72 mg/mL ( (199.42 mM) ；DMSO吸濕會降低化合物溶解度，請使用新開封DMSO) Ethanol : 72 mg/mL (199.42 mM) Water : Insoluble |
摩爾濃度計算器 |
|
體內(nèi)溶解度 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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