Idelalisib (CAL-101)
别名: GS-1101 中文名称：艾代拉里斯，艾代拉利司
Idelalisib (CAL-101)是选择性p110δ抑制剂，在无细胞试验中IC50为 2.5 nM；对 p110δ 表现出的选择性是对 p110α/β/γ 的 40 到 300 倍，对p110δ的选择性是对 C2β，hVPS34，DNA-PK 和 mTOR的400到4000倍。Idelalisib 还可诱导自噬。
Idelalisib (CAL-101) Chemical Structure
CAS: 870281-82-6
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批次：
纯度：
99.93%
99.93
Idelalisib (CAL-101)相关产品
相关信号通路图
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 |
|---|---|---|---|---|---|
| SR786 | Growth Inhibition Assay | 10 μM | 72 h | does not induce apoptosis | 22801959 |
| Myla | Growth Inhibition Assay | 10 μM | 72 h | does not induce apoptosis | 22801959 |
| HH | Growth Inhibition Assay | 10 μM | 72 h | Induction of apoptosis slightly | 22801959 |
| SP53 | Growth Inhibition Assay | 0.1 μM | 72 h | does not induce cell cycle arrest or apoptosis | 23676220 |
| MINO | Growth Inhibition Assay | 5 μM | 72 h | does not induce cell cycle arrest or apoptosis | 23676220 |
| MAVER-1 | Growth Inhibition Assay | 5 μM | 72 h | does not induce cell cycle arrest or apoptosis | 23676220 |
| JEKO-1 | Growth Inhibition Assay | 5 μM | 72 h | does not induce cell cycle arrest or apoptosis | 23676220 |
| JEKO-1 | Growth Inhibition Assay | 10 μM | 72 h | Inhibition of proliferation slightly | 23341541 |
| Granta-519 | Function Assay | 1 μM | 2 h | Inhibition of Akt(s473) phosphorylation | 23341541 |
| Granta-519 | Function Assay | 1 μM | 2 h | Inhibition of Akt(t308) phosphorylation | 23341541 |
| JEKO-1 | Function Assay | 1 μM | 72 h | Inhibition of Akt phosphorylation in IgM-stimulated JEKO-1 | 23341541 |
| Primary CLL cell | Function Assay | 1 μM | 15 min | Blocks BCR-induced LCP1 serine-5 activation | 24009233 |
| Microglia | Function Assay | 5 μM | 10 h | Decrease of TNFa secretion from LPS-stimulated p110δD910A/D910A microglia | 24625684 |
| Primary AML cell | Growth Inhibition Assay | 1 μM | 3 h | Suppression of rRNA synthesis | 25014775 |
| Primary AML cell | Function Assay | 1 μM | 3 h | Inhibition of GSK3 phosphorylation | 25014775 |
| Primary AML cell | Function Assay | 1 μM | 3 h | Inhibition of P70S6K phosphorylation | 25014775 |
| Primary AML cell | Function Assay | 1 μM | 3 h | Inhibition of Akt phosphorylation | 25014775 |
| K562 | Growth Inhibition Assay | 1 μM | 72 h | Inhibition of proliferation | 25014775 |
| K562 | Function Assay | 1 μM | 3 h | Inhibition of GSK3 phosphorylation | 25014775 |
| K562 | Function Assay | 1 μM | 3 h | Inhibition of P70S6K phosphorylation | 25014775 |
| K562 | Function Assay | 1 μM | 3 h | Inhibition of Akt phosphorylation | 25014775 |
| U266 | Growth Inhibition Assay | 40 μM | 48 h | 79.5% inhibition rate | 25339332 |
| HuT78 | Growth Inhibition Assay | 10 μM | 72 h | does not induce apoptosis | 22801959 |
| MJ | Growth Inhibition Assay | 10 μM | 72 h | does not induce apoptosis | 22801959 |
| DERL7 | Growth Inhibition Assay | 10 μM | 72 h | does not induce apoptosis | 22801959 |
| L1236 | Function Assay | 10 μM | 2 h | Inhibition of Akt phosphorylation | 22210877 |
| L428 | Function Assay | 10 μM | 2 h | Inhibition of Akt phosphorylation | 22210877 |
| L591 | Function Assay | 10 μM | 2 h | Inhibition of Akt phosphorylation | 22210877 |
| KMH-2 | Function Assay | 10 μM | 2 h | Inhibition of Akt phosphorylation | 22210877 |
| L1236 | Function Assay | 5 μM | 24 h | Blocks secretion of the CCL5 | 22210877 |
| L591 | Function Assay | 5 μM | 24 h | Blocks secretion of the CCL5 | 22210877 |
| L1236 | Apoptosis Assay | 5 μM | 24 h | Induction of apoptosis | 22210877 |
| L591 | Apoptosis Assay | 5 μM | 24 h | Induction of apoptosis | 22210877 |
| U-87MG | Function Assay | 100 nM | 24 h | Inhibition of cell migration | 22079609 |
| SW1783 | Function Assay | 100 nM | 24 h | Inhibition of cell migration | 22079609 |
| U-87MG | Function Assay | 5 μM | 24 h | Inhibition of Akt phosphorylation substantially | 22079609 |
| SW1783 | Function Assay | 5 μM | 24 h | Inhibition of Akt phosphorylation substantially | 22079609 |
| U-373MG | Function Assay | 5 μM | 24 h | Inhibition of Akt phosphorylation substantially | 22079609 |
| SK-MG3 | Function Assay | 5 μM | 24 h | Inhibition of Akt phosphorylation substantially | 22079609 |
| SU-DHL-5 | Function Assay | 1 μM | 24 h | Induction of apoptosis | 20959606 |
| WSU-NHL | Function Assay | 1 μM | 24 h | Induction of apoptosis | 20959606 |
| CCRF-SB | Function Assay | 1 μM | 24 h | Induction of apoptosis | 20959606 |
| INA-6 | Function Assay | 5 μM | 6 h | Inhibition of PI3K/Akt and ERK pathway | 20505158 |
| LB | Function Assay | 5 μM | 6 h | Inhibition of PI4K/Akt and ERK pathway | 20505158 |
| MOLM14 | Antitumor assay | 100 mg/kg | 14 days | Antitumor activity against human MOLM14 cells xenografted in nu/nu mouse assessed as tumor growth inhibition at 100 mg/kg, po administered daily via gavage dosed for 14 days and measured daily during compound dosing relative to control | 30053721 |
| MOLM14 | Antitumor assay | 100 mg/kg | 14 days | Antitumor activity against human MOLM14 cells xenografted in nu/nu mouse assessed as induction of apoptosis at 100 mg/kg, po administered daily via gavage dosed for 14 days and measured daily during compound dosing by TUNEL based assay | 30053721 |
| MOLM14 | Antitumor assay | 100 mg/kg | 14 days | Antitumor activity against human MOLM14 cells xenografted in nu/nu mouse assessed as inhibition of tumor proliferation 100 mg/kg, po administered daily via gavage dosed for 14 days and measured daily during compound dosing by Ki-67 labelling based immunoh | 30053721 |
| MOLM14 | Antiproliferative assay | 3 days | Antiproliferative activity against human MOLM14 cells after 3 days by CellTiter-Glo assay, IC50 = 3.6 μM. | 27774127 | |
| MV4-11 | Antiproliferative assay | 3 days | Antiproliferative activity against human MV4-11 cells after 3 days by CellTiter-Glo assay, IC50 = 6.3 μM. | 27774127 | |
| Jurkat | Antiproliferative assay | 3 days | Antiproliferative activity against human Jurkat cells after 3 days by CellTiter-Glo assay, IC50 = 7.9 μM. | 27774127 | |
| Loucy | Antiproliferative assay | 3 days | Antiproliferative activity against human Loucy cells after 3 days by CellTiter-Glo assay, IC50 = 8.4 μM. | 27774127 | |
| MOLT4 | Antiproliferative assay | 3 days | Antiproliferative activity against human MOLT4 cells after 3 days by CellTiter-Glo assay, IC50 = 10.6 μM. | 27774127 | |
| SUDHL6 | Antiproliferative assay | 72 hrs | Antiproliferative activity against human SUDHL6 cells measured after 72 hrs by alamar blue assay, IC50 = 0.1176 μM. | 27846451 | |
| SU-DHL4 | Antiproliferative assay | 72 hrs | Antiproliferative activity against human SU-DHL4 cells measured after 72 hrs by alamar blue assay, IC50 = 1.6 μM. | 27846451 | |
| Pfeiffer | Antiproliferative assay | 72 hrs | Antiproliferative activity against human Pfeiffer cells measured after 72 hrs by alamar blue assay, IC50 = 6.8 μM. | 27846451 | |
| KARPAS422 | Antiproliferative assay | 72 hrs | Antiproliferative activity against human KARPAS422 cells measured after 72 hrs by alamar blue assay, IC50 = 8.1 μM. | 27846451 | |
| Sf21 | Function assay | 30 mins | Inhibition of N-terminal His6-tagged recombinant full-length human PI3K p110beta/untagged recombinant full length human p85alpha expressed in baculovirus infected Sf21 insect cells using PIP2/ATP as substrate after 30 mins by TR-FRET assay, IC50 = 3.7 μM. | 28106991 | |
| Sf21 | Function assay | 30 mins | Inhibition of N-terminal His6-tagged recombinant full-length human PI3K p110beta/untagged recombinant full length human p85alpha expressed in baculovirus infected Sf21 insect cells using PIP2/ATP as substrate after 30 mins by TR-FRET assay, IC50 = 3.7 μM. | 28106991 | |
| RPMI8266 | Antiproliferative assay | 72 hrs | Antiproliferative activity against human RPMI8266 cells after 72 hrs by MTT assay, IC50 = 0.00549 μM. | 28325601 | |
| Raji | Antiproliferative assay | 72 hrs | Antiproliferative activity against human Raji cells after 72 hrs by MTT assay, IC50 = 0.00995 μM. | 28325601 | |
| SUDHL6 | Antiproliferative assay | 72 hrs | Antiproliferative activity against human SUDHL6 cells after 72 hrs by CCK8 assay, IC50 = 0.65 μM. | 29534936 | |
| RPMI8226 | Antiproliferative assay | 72 hrs | Antiproliferative activity against human RPMI8226 cells after 72 hrs by MTT assay, IC50 = 5.49 μM. | 29534936 | |
| Raji | Antiproliferative assay | 72 hrs | Antiproliferative activity against human Raji cells after 72 hrs by MTT assay, IC50 = 9.95 μM. | 29534936 | |
| MOLM13 | Growth inhibition assay | 72 hrs | Growth inhibition of human MOLM13 cells after 72 hrs by CellTiter-Glo luminescent assay, GI50 = 1.7 μM. | 30053721 | |
| MOLM14 | Growth inhibition assay | 72 hrs | Growth inhibition of human MOLM14 cells after 72 hrs by CellTiter-Glo luminescent assay, GI50 = 6.4 μM. | 30053721 | |
| CLL PBMCs | Growth Inhibition Assay | IC50=2.9 nM | 25917267 | ||
| MEC1 | Growth Inhibition Assay | IC50=20.4 μM | 25999352 | ||
| B-cells | Function assay | Inhibition of PI3Kdelta in B-cells by proliferation assay, IC50 = 0.0061 μM. | 22924688 | ||
| insect cells | Function assay | Inhibition of recombinant human full length His-tagged PI3Kgamma expressed in insect cells, IC50 = 0.089 μM. | 27846451 | ||
| insect cells | Function assay | Inhibition of recombinant human full length His-tagged PI3Kbeta expressed in insect cells, IC50 = 0.565 μM. | 27846451 | ||
| KARPAS422 | Growth inhibition assay | Growth inhibition of human KARPAS422 cells by CCK8 assay, GI50 = 0.68 μM. | 28835805 | ||
| Pfeiffer | Growth inhibition assay | Growth inhibition of human Pfeiffer cells by CCK8 assay, GI50 = 0.74 μM. | 28835805 | ||
| Saos-2 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 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 | ||
| 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 | ||
| NB1643 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 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 | ||
| Rh41 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 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 | ||
| SU-DHL6 | Growth inhibition assay | Growth inhibition of human SU-DHL6 cells by CellTiter-Glo assay, GI50 = 0.042 μM. | 29601991 | ||
| 点击查看更多细胞系数据 | |||||
生物活性
| 产品描述 | Idelalisib (CAL-101)是选择性p110δ抑制剂，在无细胞试验中IC50为 2.5 nM；对 p110δ 表现出的选择性是对 p110α/β/γ 的 40 到 300 倍，对p110δ的选择性是对 C2β，hVPS34，DNA-PK 和 mTOR的400到4000倍。Idelalisib 还可诱导自噬。 | ||||
|---|---|---|---|---|---|
| 特性 | Calistoga 暗示 CAL-101治疗血液恶性肿瘤可能有更广泛的应用价值。 | ||||
| 靶点 |
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| 体外研究(In Vitro) | ||||
| 体外研究活性 | CAL-101 对p110α, p110β,和p110γ作用效果不大。CAL-101作用于原代嗜碱细胞特定阻断FcϵR1 p110δ调节的 CD63表达，EC50 为8 nM。与急性髓性白血病(AML) 和骨髓增生性肿瘤(MPN) 细胞相比，CAL-101 作用于B-cell急性淋巴细胞白血病(B-ALL)和慢性淋巴细胞白血病(CLL) 细胞时显示更强的活性。CAL-101 作用于SU-DHL-5, KARPAS-422 和CCRF-SB细胞，降低pAktS473, pAktT308, 和下游靶点S6， EC50为0.1到1.0 μM。 [1] CAL-101 作用于CLL细胞，诱导选择性细胞毒性，不是通过突变状态或间期细胞遗传学,主要通过caspase依赖机制。与正常B细胞相比，CAL-101作用于CLL 细胞优先产生细胞毒性，和LY294002相比，作用于其他造血细胞不会产生毒性。CAL-101 作用于T 细胞和天然杀伤细胞 缺乏直接的细胞毒性潜能。CAL-101抑制炎症细胞因子的产生,比如 IL-6, IL-10, TNF-α,和IFN-γ,且激活诱导的细胞因子,如CD40L。CAL-101 也抗CD40L调节的CLL细胞存活。[2] CAL-101 作用于L1236和L591细胞, 诱导细胞在G1期积累，在S期下降，说明 CAL-101可以作为治疗霍杰金淋巴瘤(HL)的一种新策略。[3] |
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| 激酶实验 | PI3K实验 | |||
| 用全CLL和正常B细胞溶解物进行PI3K实验。 进行PI3K ELISA 实验。全细胞抽提物加到PI(4,5)P2 底物和反应 buffer（包含 ATP)的混合物中，在室温下温育。加入 PI(3,4,5)P3 探测器和 EDTA混合，反应终止，在室温下温育1小时。混合物转移到PI3K ELISA板上，再温育1小时。 冲洗反应板，然后和第二探测器再温育30分钟。再次冲洗反应板, 加入3,3′,5,5′-四甲基联苯胺溶液 ，反应5分钟，加入H2SO4 终止反应。在450纳米处读数。 | ||||
| 细胞实验 | 细胞系 | CLL B 细胞或健康志愿者的T细胞或NK细胞 | ||
| 浓度 | 0.01-100 μM | |||
| 孵育时间 | 48小时 | |||
| 方法 | 进行MTT实验测定细胞毒性。1×105个细胞和CAL-101一起温育。加入MTT试剂, 再次温育20小时，然后用溶于PBS的硫酸鱼精蛋白冲洗。加入DMSO, 用分光光度计在540纳米处测定吸光度。使用膜联蛋白/PI液式细胞计检查在不同时间点测定细胞存活力，分析数据。每个样本至少计数104个细胞。以全部阳性细胞与未处理细胞之比百分数的形式来表示实验结果。加入100 μM Z-VAD检测caspase-依赖的细胞凋亡。加入 1 μg/mL CD40L, 800 U/mL IL-4, 50 ng/mL BAFF, 20 ng/mL TNF-α测定存活信号, 或者共培养在纤连蛋白或 HS-5 细胞系基质包被的板上。 基质共培养 在75cm2培养瓶 (80%-100% 融合率) 培养24 小时，然后加入CLL细胞。 |
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| 实验图片 | 检测方法 | 检测指标 | 实验图片 | PMID |
| Western blot | PUMA / p53 Bim / Bcl-xl / Bid / Mcl-1 p-p65 p-AKT / AKT Cleaved caspase 3 / Cleaved caspase 9 Mcl-1 / Bcl-2 / Bid / Bcl-xl / Noxa / Bak / Bax p-FoxO3a / FoxO3a Akt(T308) / PDK1(S241) / GSK-3β(S9) |
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28008149 | |
| Growth inhibition assay | Cell viability Cell viability |
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28008149 | |
| NCT Number | Recruitment | Conditions | Sponsor/Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| NCT03582098 | Completed | Chronic Lymphocytic Leukaemia |
Gilead Sciences |
September 12 2018 | -- |
| NCT03151057 | Terminated | B Cells-Tumors|B Cell Chronic Lymphocytic Leukemia|Follicular Lymphoma|Mantle Cell Lymphoma|Large B-Cell Diffuse Lymphoma of Bone (Diagnosis) |
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins|Gilead Sciences |
July 31 2018 | Phase 1 |
| NCT03568929 | Completed | Follicular Non-Hodgkin''s Lymphoma Refractory |
Gilead Sciences |
May 25 2018 | -- |
化学信息&溶解度
| 分子量 | 415.42 | 分子式 | C22H18FN7O |
| CAS号 | 870281-82-6 | SDF | Download Idelalisib (CAL-101) SDF |
| Smiles | CCC(C1=NC2=C(C(=CC=C2)F)C(=O)N1C3=CC=CC=C3)NC4=NC=NC5=C4NC=N5 | ||
| 储存条件(自收到货起) | |||
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体外溶解度 |
DMSO : 83 mg/mL ( (199.79 mM) ；DMSO吸湿会降低化合物溶解度，请使用新开封DMSO) Water : Insoluble Ethanol : Insoluble |
摩尔浓度计算器 |
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体内溶解配方 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）
mg/kg
g
μL
只
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）
% DMSO
%
% Tween 80
% ddH2O
%DMSO
%
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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常见问题及建议解决方法
问题 1:
What is the recommended dose of CAL-101 and the route of administration for mouse studies?
回答：
According to the following paper, S2226 can be used by I.V. administration at the concentration of 40 mg/kg. https://www.ncbi.nlm.nih.gov/pubmed/24625684
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