Ibrutinib

製品コードS2680 バッチS268011

印刷

化学情報

Chemical Structure Synonyms PCI-32765 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C25H24N6O2
分子量 440.5 CAS No. 936563-96-1
Solubility (25°C)* 体外 DMSO 88 mg/mL (199.77 mM)
Ethanol 45 mg/mL warmed with 50ºC water bath (102.15 mM)
Water Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 イブルチニブ (Ibrutinib (PCI-32765)) は、無細胞アッセイで IC50 が 0.5 nM の強力で選択性の高い Brutons チロシンキナーゼ (Brutons tyrosine kinase, Btk) 阻害剤であり、Bmx, CSK, FGR, BRK, HCKに対しても阻害活性を持ちます。 EGFR, Yes, ErbB2, JAK3 に対しては前者より比較的弱い活性を持ちます。イブルチニブは、P13I を含む一連の PROTAC の合成における Btk リガンドとして適用できます。
in vitro

Ibrutinib shows the potent and irreversible inhibitory effect and selectivity for Btk enzymatic activity. In BCR pathway-activated DOHH2 cell line, Ibrutinib inhibits autophosphorylation of Btk, phosphorylation of Btk's physiological substrate PLCγ, and phosphorylation of further downstream kinase, ERK with IC50 of 11 nM, 29 nM and 13 nM, respectively. [1] Ibrutinib exhibits a significant dose-dependent and time-dependent induction of cytotoxicity in chronic lymphocytic leukemia (CLL) cells. In addition, Ibrutinib induces cell death depending on caspase pathway activation and antagonizes the ability of CLL cells to proliferate after TLR signaling. [2] A recent study shows that Ibrutinib inhibits BCR-activated primary B cell proliferation with IC50 of 8 nM and results in inhibition of TNFα, IL-1β and IL-6 production in primary monocytes with IC50 of 2.6 nM, 0.5 nM and 3.9 nM, respectively. [3]
in vivo

In a collagen-induced arthritis model, Ibrutinib significantly reduces clinical arthritis scores reflecting paw swelling and joint inflammation by inhibiting B-cell activation. In a MRL-Fas(lpr) lupus model, Ibrutinib reduces renal disease and autoantibody production. [1] In an adoptive transfer TCL1 mouse model of CLL, Ibrutinib (25 mg/kg/day) causes a transient early lymphocytosis, and delays CLL disease progression. [4]

プロトコル(参考用のみ)

キナーゼアッセイ Kinase Assays
In vitro kinase IC50 values are measured using 33P filtration binding assay after 1 hour incubation of kinase, 33P-ATP, Ibrutinib, and substrate [0.2 mg/mL poly(EY)(4:1]. Assays are performed at Reaction Biology.
細胞アッセイ 細胞株 Chronic lymphocytic leukemia (CLL) cells
濃度 0.01-100 μM
反応時間 48 hours
実験の流れ

MTT (3'[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide) assays are performed to determine cytotoxicity. Briefly, cells (CLL B cells or healthy volunteer T cells or NK cells) are incubated for 48 hours with different concentrations of Ibrutinib, or vehicle control. MTT reagent is then added, and plates are incubated for an additional 20 hours before washing with protamine sulfate in phosphate-buffered saline. Dimethyl sulfoxide is added, and absorbance is measured by spectrophotometry at 540 nm in a Labsystems plate reader. Cell viability is also measured at various time points with the use of annexin/PI flow cytometry. Data are analyzed with Expo-ADC32 software package. Results are expressed as the percentage of total positive cells over untreated control. Experiments examining caspase-dependent apoptosis includes the addition of 100μM Z-VAD.
動物実験 動物モデル MRL-Fas(lpr) lupus model and collagen-induced arthritis model.
投薬量 ≤50 mg/kg
投与方法 Administered via p.o.

カスタマーフィードバック

Data from [Data independently produced by J Cell Sci, 2015, 128(2), 251-65]

Data from [Data independently produced by J Biol Chem, 2015, 290(18), 11557-68]

Data from [Data independently produced by Blood Cancer J, 2014, 4, e181]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Dual Inhibition of CDK4/6 and XPO1 Induces Senescence With Acquired Vulnerability to CRBN-Based PROTAC Drugs [ Gastroenterology, 2024, S0016-5085(24)00062-3] PubMed: 38262581
T-bet+ B cells are activated by and control endogenous retroviruses through TLR-dependent mechanisms [ Nat Commun, 2024, 15(1):1229] PubMed: 38336876
EFNB1 levels determine distinct drug response patterns guiding precision therapy for B-cell neoplasms [ iScience, 2024, 27(1):108667] PubMed: 38155773
Ibrutinib-induced pulmonary angiotensin-converting enzyme activation promotes atrial fibrillation in rats [ iScience, 2024, 27(2):108926] PubMed: 38357670
CAD204520 Targets NOTCH1 PEST Domain Mutations in Lymphoproliferative Disorders [ Int J Mol Sci, 2024, 25(2)766] PubMed: 38255842
ATI-1777, a Topical Jak1/3 Inhibitor, May Benefit Atopic Dermatitis without Systemic Drug Exposure: Results from Preclinical Development and Phase 2a Randomized Control Study ATI-1777-AD-201 [ JID Innov, 2024, 4(2):100251] PubMed: 38299059
B cell receptor signaling in germinal centers prolongs survival and primes B cells for selection [ Immunity, 2023, 56(3):547-561.e7] PubMed: 36882061
E-selectin-mediated rapid NLRP3 inflammasome activation regulates S100A8/S100A9 release from neutrophils via transient gasdermin D pore formation [ Nat Immunol, 2023, 10.1038/s41590-023-01656-1] PubMed: 37903858
Dasatinib overcomes glucocorticoid resistance in B-cell acute lymphoblastic leukemia [ Nat Commun, 2023, 14(1):2935] PubMed: 37217509
BMX controls 3βHSD1 and sex steroid biosynthesis in cancer [ J Clin Invest, 2023, 133(2)e163498] PubMed: 36647826

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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