CAL-101 (Idelalisib, GS-1101)
(Synonyms: 艾代拉里斯; CAL-101; GS-1101) 目录号 : GC13396
A selective PI3K p110δ inhibitor
Cas No.:870281-82-6
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment: [1] | |
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Cell lines |
CD19/CD5-positive CLL cells (> 90%) |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months. |
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Reaction Conditions |
< 5 μM: dose-dependently inhibits the pro-survival effect of anti-IgM = 5 μM, 24h: inhibits 2.6% activity of anti-IgM > 5 μM, 72h: maximally reduces CLL cell viability |
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Applications |
CAL-101 abrogated the pro-survival effect of anti-IgM in a dose-dependent fashion at lower dose levels (< 5 μM). CAL-101 treatment at concentrations of > 5 μM was maximally effective over the 72-hour time course in reducing CLL cell viability. At the 5 μM concentration, CAL-101 significantly decreased the mean ( SEM) pro-survival effect of anti-IgM to 92.7% ( 2.6%) after 24 hours. |
| Animal experiment : [2] | |
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Animal models |
NOD-SCID-γ-null (NSG) mice well-engrafted with de novo (n = 3) or relapsed (n = 1) childhood Ph-like ALL specimens with JAK2 mutations and/or CRLF2 alterations. |
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Dosage form |
30 mg/kg/day, 3 days, oral gavage |
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Applications |
CAL101 treatments demonstrated potent in vivo inhibition of relevant phosphoproteins, including phosphorylated (p) PI3K, mTOR, S6, and AktS473. Increased phosphorylation of other measured proteins was not observed, suggesting that proximal inhibition effectively abrogated aberrant PI3K pathway signal transduction with minimal compensatory signaling upregulation. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1] Hoellenriegel J, Meadows S A, Sivina M, et al. The phosphoinositide 3′-kinase delta inhibitor, CAL-101, inhibits B-cell receptor signaling and chemokine networks in chronic lymphocytic leukemia. Blood, 2011, 118(13): 3603-3612. [2] Li Y, Ryan T, Vincent T, et al. In vivo efficacy of PI3K pathway signaling inhibition for Philadelphia chromosome-like acute lymphoblastic leukemia. Blood, 2013, 122(21): 2672-2672. | |
CAL-101 (Idelalisib, GS-1101), is a p110δ selective phosphatidylinositol-3-kinase inhibitor in a kinome-wide screen using purified enzymes and in cell-based PI3K isoform-specific assays. Phosphatidylinositol-3-kinase p110δ serves as a central integration point for signaling from cell surface receptors known to promote malignant B-cell proliferation and survival. CAL-101 can block constitutive phosphatidylinositol-3-kinase signaling, resulting in reduced phosphorylation of Akt and other downstream effect factors, an increase in poly(ADP-ribose) polymerase and caspase cleavage and an induction of apoptosis. These effects have been observed across a broad range of immature and mature B-cell malignancies. In addition, CAL-101 abrogated protection from spontaneous apoptosis induced by B cell–activating factors CD40L, TNF-α, and fibronectin.
Reference
[1].Brian J. Lannutti, Sarah A. Meadows, Sarah E. M. Herman, Adam Kashishian, Bart Steiner, Amy J. Johnson, John C. Byrd, Jeffrey W. Tyner, Marc M. Loriaux, Mike Deininger, Brian J. Druker, Kamal D. Puri, Roger G. Ulrich, and Neill A. Giese. CAL-101, a p110δ selective phosphatidylinositol-3-kinase inhibitor for the treatment of B-cell malignancies, inhibits PI3K signaling and cellular viability. Blood. 2011; 117(2): 591 – 594.
[2].Sarah E. M. Herman, Amber L. Gordon, Amy J. Wagner, Nyla A. Heerema, Weiqiang Zhao, Joseph M. Flynn, Jeffrey Jones, Leslie Andritsos, Kamal D. Puri, Brian J. Lannutti, Neill A. Giese, Xiaoli Zhang, Lai Wei, John C. Byrd, Amy J. Johnson. Phosphatidylinositol 3-kinase-δ inhibitor CAL-101 shows promising preclinical activity in chronic lymphocytic leukemia by antagonizing intrinsic and extrinsic cellular survival signals. Blood. 2010; 116(12): 2078 – 88.
| Cas No. | 870281-82-6 | SDF | |
| 别名 | 艾代拉里斯; CAL-101; GS-1101 | ||
| 化学名 | 5-fluoro-3-phenyl-2-[(1S)-1-(7H-purin-6-ylamino)propyl]quinazolin-4-one | ||
| Canonical SMILES | CCC(C1=NC2=C(C(=CC=C2)F)C(=O)N1C3=CC=CC=C3)NC4=NC=NC5=C4NC=N5 | ||
| 分子式 | C22H18FN7O | 分子量 | 415.43 |
| 溶解度 | ≥ 80.2 mg/mL in DMSO, ≥ 2.1 mg/mL in EtOH with ultrasonic and warming | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.4071 mL | 12.0357 mL | 24.0714 mL |
| 5 mM | 0.4814 mL | 2.4071 mL | 4.8143 mL |
| 10 mM | 0.2407 mL | 1.2036 mL | 2.4071 mL |
| 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） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 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GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
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，
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 saline，混匀澄清。
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。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Abstract
CAL-101 is a highly selective inhibitor of p110δ.
Abstract
CAL-101 is a selective inhibitor of PI3Kδ that induces rapid lymph node shrinkage and a transient lymphocytosis in CLL cells. CAL-101 not only directly inhibits the pro-survival PI3K pathway but also disrupts CLL-microenvironment interactions, where it inhibits chemotaxis and migration of CLL cell, down-regulates BCR-induced chemokines secretion, reduces survival signals and suppresses ERK activation.
Abstract
CAL-101, an oral inhibitor of PI3Kδ, inhibited AKT phosphorylation and stroma-induced Akt activation, reduced CCL5 production and dose-dependently induced apoptosis in HL cells. Moreover, addition of everolimu could enhance the anti-HL activity of CAL-101.
Abstract
CAL-101 is an inhibitor of p110δ that blocks phosphatidylinositol-3-kinase signaling in a wide range of B-cell malignancies leading to decreased phosphorylation of Akt and other downstream effectors, increased polu(ADP-ribose) polymerase and caspase cleavage and induced apoptosis.
Abstract
CAL-101, a p110 delta inhibitor, has been developed fr the treatment of chronic lymphoid malignancies including CLL.