CAL-101 (Idelalisib, GS-1101)
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
CAL-101(Idelalisib,GS-1101)是一个选择性的PI3K(磷脂酰肌醇-3-激酶)p110δ的抑制剂。
PI3K p110δ可以被促进恶性B细胞增殖和存活的细胞表面受体信号所激活。CAL-101可以阻断持续性的PI3K信号,减少Akt及其它下游效应因子的磷酸化,增加聚(ADP-核糖)聚合酶(PARP)和caspase加工,诱导细胞凋亡。这些效果可以在一系列未成熟和成熟B细胞的恶性肿瘤中观察到。此外,CAL-101拮抗B细胞活化因子CD40L、TNF-α和纤连蛋白诱导的对自发凋亡的抑制。
参考文献:
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.
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.
- 1. Daniel Pinto-Benito, Carmen Paradela-Leal, et al. "IGF-1 regulates astrocytic phagocytosis and inflammation through the p110α isoform of PI3K in a sex-specific manner." Glia. 2022 Jun;70(6):1153-1169. PMID: 35175663
- 2. Graeme F. Murray, Daniel Guest, et al. "Single cell biomass tracking allows identification and isolation of rare targeted therapy-resistant DLBCL cells within a mixed population." Analyst. 2021 Feb 21;146(4):1157-1162. PMID: 33426547
- 3. Julia C Gutjahr, Elisabeth Bayer, et al. "CD44 Engagement Enhances Acute Myeloid Leukemia Cell Adhesion To The Bone Marrow Microenvironment By Increasing VLA-4 Avidity." Haematologica. 2020 Jul 2;haematol.2019.231944. PMID: 32616529
- 4. Wu W, Zhou G, et al. "PI3Kδ as a Novel Therapeutic Target in Pathological Angiogenesis." Diabetes. 2020;db190713. PMID: 31915155
- 5. Xin T, Han H, et al. "Idelalisib inhibits vitreous-induced Akt activation and proliferation of retinal pigment epithelial cells from epiretinal membranes." Exp Eye Res. 2019 Nov 28:107884. PMID: 31786159
- 6. Han H, Chen N, et al. "Phosphoinositide-3-kinase δ inactivation prevents vitreous-induced activation of AKT/MDM2/p53 and migration of retinal pigment epithelial cells." J Biol Chem. 2019 Aug 29. pii: jbc.RA119.010130. PMID: 31467081
- 7. Yaya Chu, Sanghoon Lee, et al. " Ibrutinib significantly inhibited Bruton’s tyrosine kinase (BTK) phosphorylation,in-vitro proliferation and enhanced overall survival in a preclinical Burkitt lymphoma (BL) model." OncoImmunology.11 Oct 2018.
- 8. Wensveen FM, Slinger E, et al. "Antigen-affinity controls pre-germinal centser B cell selection by promoting Mcl-1 induction through BAFF receptor signaling." Sci Rep. 2016 Oct 20;6:35673. PMID: 27762293
Physical Appearance | A solid |
Storage | Store at -20°C |
M.Wt | 415.43 |
Cas No. | 870281-82-6 |
Formula | C22H18FN7O |
Synonyms | CAL-101,CAL101,Idelalisib,GS-1101,GS1101 |
Solubility | insoluble in H2O; ≥2.1 mg/mL in EtOH with gentle warming and ultrasonic; ≥80.2 mg/mL in DMSO |
Chemical Name | 5-fluoro-3-phenyl-2-[(1S)-1-(7H-purin-6-ylamino)propyl]quinazolin-4-one |
SDF | Download SDF |
Canonical SMILES | CCC(C1=NC2=C(C(=CC=C2)F)C(=O)N1C3=CC=CC=C3)NC4=NC=NC5=C4NC=N5 |
运输条件 | 蓝冰运输或根据您的需求运输。 |
一般建议 | 不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。溶液形式一般不宜长期储存,请尽快用完。 |
细胞实验[1]: | |
细胞系 |
CD19/CD5阳性CLL细胞(> 90%) |
溶解方法 |
在DMSO中的溶解度>10 mM。为了获得更高的浓度,可以将离心管在37℃加热10分钟和/或在超声波浴中震荡一段时间。原液可以在-20℃以下储存几个月。 |
反应条件 |
< 5 μM:剂量依赖地抑制anti-IgM的促存活效应;= 5 μM,24h:抑制2.6%的anti-IgM活性;> 5 μM,72h:最大限度地减少CLL细胞的活力。 |
应用 |
CAL-101在较低剂量水平(< 5 μM)以剂量依赖的方式抑制anti-IgM的促存活效应。CAL-101在大于 5 μM浓度下处理72小时后最大限度地减少CLL细胞的活力。在5 μM浓度下处理24小时后,CAL-101显著减少了2.6%的anti-IgM的平均(SEM)促存活效应(92.7%)。 |
动物实验[2]: | |
动物模型 |
异种移植含有JAK2突变和/或CRLF2改变的从头(n=3)或复发(n=1)儿童Ph-样ALL样本的NOD-SCID-γ-null (NSG) 小鼠。 |
剂量 |
30 mg/kg/天,3天,口服给药。 |
应用 |
CAL101治疗可以有效抑制体内相关蛋白的磷酸化,包括磷酸化的(p)PI3K、mTOR、S6和AktS473,没有观察到其它已测蛋白磷酸化的增加,表明近端抑制有效抑制异常PI3K途径的信号转导,并诱导最小的补偿性信号上调。 |
注意事项 |
请测试所有化合物在室内的溶解度,实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的,属于正常现象。 |
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. |
描述 | CAL-101 (Idelalisib, GS-1101)是一个选择性的p110δ抑制剂,IC50值为2.5 nM。 | |||||
靶点 | p110δ | |||||
IC50 | 2.5 nM |
质量控制和MSDS
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