產(chǎn)地	國產(chǎn)	規(guī)格	5mg
級別	化工級	證書	ISO系列證書

Ibrutinib (Synonyms: 伊布替尼; PCI-32765)

Ibrutinib (PCI-32765) 是一種不可逆的選擇性 Btk 抑制劑，IC₅₀ 值為 0.5 nM。Ibrutinib 可作為 Btk 配體，用于合成一系列 PROTAC 分子，如 P13I。P13I 作用于人 Burkitt’s 淋巴瘤 RAMOS 細胞，濃度為 10 和 100?nM 時，分別降解 73% 和 89% Btk。

生物活性

Ibrutinib (PCI-32765) is a selective, irreversible Btk inhibitor with an IC₅₀ of 0.5 nM^[1].

IC₅₀ & Target

IC50: 0.5 nM (Btk)

體外研究(In Vitro)

Ibrutinib (PCI-32765) selectively inhibits B-cell signaling and activation. It inhibits autophosphorylation of Btk (IC₅₀=11 nM), phosphorylation of Btk's physiological substrate PLCγ (IC₅₀=29 nM), and phosphorylation of a further downstream kinase, ERK (IC₅₀=13 nM)^[1].
Ibrutinib (PCI-32765) inhibits BCR-activated primary B cell proliferation (IC₅₀=8 nM). Following FcγR stimulation, Ibrutinib (PCI-32765) inhibits TNFα, IL-1β and IL-6 production in primary monocytes (IC₅₀=2.6, 0.5, 3.9 nM, respectively)^[3].
Ibrutinib binds C481 (Cysteine481) of BTK with an ideal IC₅₀ of 0.5?nM. Ibrutinib cannot form a covalent bond with the hydroxyl group of serine, C481S mutation increases the IC₅₀ against BTK-C481S phosphorylation from 2.2?nM to 1?μM^[4].

體內(nèi)研究(In Vivo)

Ibrutinib (PCI-32765) (3.125-50 mg/kg, p.o.) reduces the level of circulating autoantibodies and completely suppresses disease in mice with collagen-induced arthritis. Ibrutinib (PCI-32765) inhibits autoantibody production and the development of kidney disease in the MRL-Fas(lpr) lupus model. Ibrutinib (PCI-32765) (3.125-50 mg/kg, p.o.) reduces renal disease and autoantibody production in MRL-Fas(lpr) mice^[1]. Ibrutinib (PCI-32765) (0.1 μM) inhibits activation-induced proliferation of CLL cells, induces selective cytotoxicity in B cells compared with T cells, but alters activation induced T-cell cytokine production^[2]. Ibrutinib (PCI-32765) dose-dependently and potently reverses arthritic inflammation in a therapeutic CIA model with an ED₅₀ of 2.6 mg/kg/day. Ibrutinib (PCI-32765) also prevents clinical arthritis in CAIA models^[3].

分子量：440.50

性狀：Solid

Formula：C₂₅H₂₄N₆O₂

CAS 號：936563-96-1

中文名稱：依魯替尼；伊布魯替尼；伊布替尼

運輸條件：Room temperature in continental US; may vary elsewhere.

儲存方式

4°C, protect from light

*In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)

溶解性數(shù)據(jù)

In Vitro:

DMSO : 100 mg/mL (227.01 mM; Need ultrasonic)

配制儲備液

濃度溶劑體積質(zhì)量	1 mg	5 mg	10 mg

1 mM	2.2701 mL	11.3507 mL	22.7015 mL
5 mM	0.4540 mL	2.2701 mL	4.5403 mL
10 mM	0.2270 mL	1.1351 mL	2.2701 mL

請根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；一旦配成溶液，請分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。
儲備液的保存方式和期限：-80°C, 6 months; -20°C, 1 month (protect from light)。-80°C 儲存時，請在 6 個月內(nèi)使用，-20°C 儲存時，請在 1 個月內(nèi)使用。

In Vivo:

以下溶解方案都請先按照 In Vitro 方式配制澄清的儲備液，再依次添加助溶劑：

——為保證實驗結(jié)果的可靠性，澄清的儲備液可以根據(jù)儲存條件，適當保存；體內(nèi)實驗的工作液，建議您現(xiàn)用現(xiàn)配，當天使用；以下溶劑前顯示的百
分比是指該溶劑在您配制終溶液中的體積占比；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的方式助溶

1.

請依序添加每種溶劑： 0.5% MC 0.5% Tween-80
Solubility: 3.33 mg/mL (7.56 mM); Suspension solution; Need ultrasonic
2.

請依序添加每種溶劑： 5% DMSO 95% (20% SBE-β-CD in saline)
Solubility: ≥ 2.75 mg/mL (6.24 mM); Clear solution
3.

請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% saline
Solubility: ≥ 2.5 mg/mL (5.68 mM); Clear solution
4.

請依序添加每種溶劑： 10% DMSO 90% (20% SBE-β-CD in saline)
Solubility: 2.5 mg/mL (5.68 mM); Suspended solution; Need ultrasonic
5.

請依序添加每種溶劑： 10% DMSO 90% corn oil
Solubility: ≥ 2.5 mg/mL (5.68 mM); Clear solution

參考文獻

[1]. Honigberg LA, et al. The Bruton tyrosine kinase inhibitor PCI-32765 blocks B-cell activation and is efficacious in models of autoimmune disease and B-cell malignancy. Proc Natl Acad Sci U S A. 2010 Jul 20;107(29):13075-80. [Content Brief]

[2]. Herman SE, et al. Bruton tyrosine kinase represents a promising therapeutic target for treatment of chronic lymphocytic leukemia and is effectively targeted by PCI-32765. Blood. 2011 Jun 9;117(23):6287-96. [Content Brief]

[3]. Chang BY, et al. The Bruton tyrosine kinase inhibitor PCI-32765 ameliorates autoimmune arthritis by inhibition of multiple effector cells. Arthritis Res Ther. 2011 Jul 13;13(4):R115. [Content Brief]

[4]. Sun Y, et al. PROTAC-induced BTK degradation as a novel therapy for mutated BTK C481S induced ibrutinib-resistant B-cell malignancies. Cell Res. 2018 Jul;28(7):779-781. [Content Brief]