Delanzomib

カタログ番号 T6027 CAS 847499-27-8

別名: CEP-18770

Delanzomib (CEP-18770) is an orally active inhibitor of the chymotrypsin-like activity of proteasome (IC50: 3.8 nM). It only marginally inhibits the tryptic and peptidylglutamyl activities of the proteosome.

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Delanzomib, CAS 847499-27-8

パッケージサイズ	在庫状況	単価(税別)
サンプルについてお問い合わせ
1 mg	在庫あり	￥ 10,000
2 mg	在庫あり	￥ 14,000
5 mg	在庫あり	￥ 24,500
10 mg	在庫あり	￥ 46,500
25 mg	在庫あり	￥ 91,500
50 mg	在庫あり	￥ 137,000
100 mg	在庫あり	￥ 189,500
1 mL * 10 mM (in DMSO)	在庫あり	￥ 26,500

バルクのお問い合わせ

バッチを選択

純度: 99.46%

COA DATASHEET SDS HNMR HPLC

純度: 95.52%

COA DATASHEET SDS HNMR HPLC

COA DATASHEET SDS

バッチの詳細情報はお問い合わせください

生物学的特性に関する説明

化学的特性

保存条件 & 溶解度情報

説明	Delanzomib (CEP-18770) is an orally active inhibitor of the chymotrypsin-like activity of proteasome (IC50: 3.8 nM). It only marginally inhibits the tryptic and peptidylglutamyl activities of the proteosome.
ターゲット＆IC50	Chymotrypsin-like proteasome:3.8 nM
In vitro	CEP-18770 demonstrates marginal prevention of the tryptic and peptidyl gultamyl activities of the protesome. The IC50 values of CEP-18770 are similar to those of bortezomib, with the chymotryptic and caspase-like activities being inhibited at low-nanomolar concentrations.[1] CEP-18770 inhibits A2780 ovarian cancer cells, PC3 prostate cancer, H460, LoVo colon cancer, RPMI8226 multiple myeloma cancer and HS-Sultan anaplastic non-Hodgkin lymphoma with IC50 values of 13.7, 22.2, 34.2 11.3, 5.6 and 8.2 nM, respectively.[1] CEP-18770 blocks the ubiquitin-proteasome pathway in several MM and in the chronic myelogenous leukemia cell line, K562. CEP-18770 causes an accumulation of ubiquitinated proteins over 4 to 8 hours with a profile similar to that observed after bortezomib treatment.[1] IκBα degradation is completely blocked by pretreatment with CEP-18770. CEP-18770 significantly inhibits high levels of NF-κB activity in both RPMI-8226 and U266 cells. The time- and concentration-dependent suppression of NF-kB DNA-binding activity in MM cell lines by CEP-18770 leads to a decrease of expression of several NF-κB-modulated genes mediating the growth and survival of tumor cells including IkBα itself, the X-chromosome-linked inhibitor-of-apoptosis protein (XIAP), the pro-inflammatory cytokines TNF-α and interleukin-1β (IL-1β), the intracellular adhesion molecule (ICAM1), and the pro-angiogeneic factor vascular endothelial growth factor. [1] The expression of these NF-κB–mediated genes and their modulation by bortezomib are associated with more favorable Clinicalal responsiveness to this agent, highlighting their potential prognostic value in response to CEP-18770 exposure.
In vivo	CEP-18770 reveals sustained dose-related relative tumor weight inhibition. CEP-18770 leads to dose-related complete tumor regressions, as compared to bortezomib treatment, which results in a 50% incidence of CR at its maximally tolerated dose (MTD) of 1.2 mg/kg intravenously. [1] In contrast to bortezomib, CEP-18770 reveals dose-related increase in the incidence of tumor-free mice by the completion of these studies (120 days after tumor transplantation). Oral administration of CEP-18770 produces a marked decrease in tumor weight and notable dose-related incidence of complete tumor regression with minimal changes in animal body weight over the course of the 120 day studies. [1]When compared to bortezomib, equiactive doses of CEP-18770 reveal a greater and more sustained dose-related inhibition of tumor proteasome activity, corresponding temporarily with maximum induction of caspase-3 and 7 activity.[1] The maximum apoptotic signal is 2.5 fold greater for CEP-18770 versus bortezomib. In contrast, proteasome inhibition profiles of CEP-18870 and bortezomib are comparable in the normal peripheral mouse tissues examined (liver, lungs, whole blood, and brain [no activity]) in both their magnitude and their duration.[1] No proteasome inhibition is detected in brain tissue at any time point for either CEP-18770 or bortezomib. In MM xenograft models, the addition of CEP-18770 to melphalan completely preventes the growth of both melphalan-sensitive or melphalan-resistant tumours. [1] The combination of CEP-18770 and bortezomib leads to complete regression of bortezomib-sensitive tumours and markedly delays progression of bortezomib-resistant tumours compared to treatment with either agent alone. Single agent CEP-18770 PO also shows marked anti-MM effects in these xenograft models[1]
キナーゼ試験	Probing proteasome activity in cell extracts: Human multiple myeloma cells are washed twice with cold phosphate-buffered saline, pelleted and lysed with one volume of glass beads (<106 microns, acid-washed) and an equal volume of homogenization buffer (50 mM Tris (pH 7.4), 1 mM dithiothreitol, 5 mM MgCl2, 2 mM ATP and 250 mM sucrose) by vortexing at high speed for 15-30 min at 4 °C. Beads, membrane fractions, nuclei and cell debris are then removed from the supernatant by centrifugation at 16,000 g for 5 min. The protein content of extracts is quantitated using the Bradford assay. Proteasome activity is assayed as described below. Equal amounts (typically 60 g) of protein are denatured by boiling in reducing sample buffer, separated by 12.5% SDS-PAGE and electrotransferred onto polyvinylidene difluoride (PVDF) membranes. Immunoblotting is performed using a dansyl-sulfonamidohexanoyl polyclonal antibody (1:7,500, rabbit) and horseradish peroxidase–coupled goat or swine anti-rabbit secondary antibody followed by enhanced chemiluminescence.
細胞研究	HMEC and TEC cells are seeded into 24-well plates at a density of 104 cells/well in DMEM supplemented with 5% FCS. After incubation with proteasome inhibitors (48 hours), cells are washed, air dried, and stained with crystal violet as described. Cell number is determined, in duplicate samples, on the basis of a standard curve obtained with known cell numbers. All experiments are performed in triplicate. In vitro formation of capillary-like structures is studied on cells (4 × 104 cells/well in DMEM supplemented with 5% FCS. After incubation with proteasome inhibitors (48 hours), cells are washed (cells/well in 24-well plates) and seeded onto Matrigel-coated wells in DMEM containing 0.25% BSA. HMEC and TEC cells (5 × 103 per well), suspended in 200 μL DMEM with 5% FCS (positive control), serum-free medium (negative control), are layered onto the Matrigel surface in the presence or absence of proteasome inhibitor CEP-18770. Cells are observed with a inverted microscope and experimental results are then recorded after a 6-hour incubation at 37 °C. Data is analyzed, as the mean (× 1 SD) of total length of capillary-like structures, by the Micro-Image system and is expressed as mm/field by the computer analysis system in 5 different fields at 100 × magnification in duplicated wells for 4 different experiments. (Only for Reference)

別名	CEP-18770
分子量	413.28
分子式	C21H28BN3O5
CAS No.	847499-27-8

保存条件

Powder: -20°C for 3 years | In solvent: -80°C for 1 year

溶解度情報

H2O: < 1 mg/mL (insoluble or slightly soluble)

Ethanol: 77 mg/mL (186.3 mM)

DMSO: 77 mg/mL (186.3 mM)

参考文献

1. Piva R,et al. Blood. 2008,111(5),2765-2775. 2. Sanchez E, et al. Br J Haematol. 2010,148(4),569-581. 3. Berkers CR, et al. Nat Methods. 2005,2(5),357-362.

引用文献

1. Chen X, Chen Y, Ou Y, et al. Bortezomib inhibits NLRP3 inflammasome activation and NF-κB pathway to reduce psoriatic inflammation. Biochemical Pharmacology. 2022, 206: 115326.

投与量変換

You can also refer to dose conversion for different animals. 詳細

In vivo投与量計算 (透明溶液)

ステップ1: 以下の情報を入力してください

投与量

mg/kg

動物の平均体重

動物あたりの投与量

動物数

溶媒の組成を入力してください

% DMSO+

% +

% Tween 80+

% ddH₂O

%DMSO+

計算するリセット

計算結果:

作業濃度: mg/ml;

DMSO溶液の作成方法: mg あらかじめ溶解した薬剤 μL DMSO (マスター溶液の濃度 mg/mL)，濃度がそのバッチの薬剤のDMSO溶解度を超える場合は、まずご連絡ください。

生体内薬剤の調合法：取る μL DMSO マスター溶液、次に追加 μL PEG300，確実に混ぜてから加える μL Tween 80，確実に混ぜてから加える μL ddH₂O, 確実に混ぜる

お問合せ内容:

必ず順番通りに溶媒を加えてください。ボルテックスミキサーや超音波、湯煎することで溶解しやすくなります

計算器

モル濃度計算機

希釈計算機

再構成計算

分子量計算機

質量

濃度

体積

分子量

モル度計算機では以下の計算が可能です

既知の体積と濃度の溶液を調製するために必要な化合物の質量
質量が既知の化合物を目的の濃度まで溶解させるのに必要な溶液の量
特定の体積の中に既知の質量の化合物を入れて得られる溶液の濃度

参考例

モル濃度計算機を使用したモル濃度計算の例
化合物の分子量が197.13g/molである場合、10mlの水に10mMのストック溶液を作るのに必要な化合物の質量はどれくらいですか？
［分子量（MW）］の欄に［197.13］と入力してください
[濃度]ボックスに10と入力し、正しい単位（millimolar）を選択します
[容量]ボックスに10と入力し、正しい単位（milliliter）を選択します
計算を押します
答えの19.713mgが質量欄に表示されます

濃度 (開始)

体積 (開始)

濃度 (終了)

体積 (終了)

溶液を作るのに必要な希釈率の計算

溶液の調製に必要な希釈率の算出
希釈計算機は、既知の濃度の原液をどのように希釈するかを計算することができる便利なツールです。V1を計算するためにC1、C2＆V2を入力します。

参考例

Tocrisの希釈計算器を用いた希釈計算の一例
50μMの溶液を20ml作るためには、10mMの原液を何ml必要ですか？
C1V1=C2V2という式を用いて、C1=10mM、C2=50μM、V2=20ml、V1を未知数とします。
濃度（開始）ボックスに10を入力し正しい単位(millimolar)を選択してください
濃度（終了）ボックスに50を入力し正しい単位(millimolar)を選択してください
体積（終了）ボックスに20を入力し正しい単位(millimolar)を選択してください
計算を押します
100 microliter (0.1 ml) という答えが体積（開始）ボックスに表示されます。

分子式

分子量 g/mol

化合物の化学式を入力して、そのモル質量や元素組成を計算します

Tヒント：化学式は大文字と小文字を区別します。: C10H16N2O2 c10h16n2o2

化合物のモル質量（分子量）を計算する手順:
化学物質のモル質量を計算するには、その化学式を入力し、「計算」をクリックしてください。.
分子質量、分子量、モル質量、モル重量の定義:
分子質量（分子量）とは、物質の1分子の質量であり、統一された原子質量単位（u）で表されます。(1uは炭素12の1原子の質量の1/12に等しい）
モル質量（molar weight）とは、ある物質の1モルの質量のことで、単位はg/molです。

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技術サポート

Please see Inhibitor Handling Instructions for more frequently ask questions. Topics include: how to prepare stock solutions, how to store products, and cautions on cell-based assays & animal experiments, etc.

Keywords

Delanzomib 847499-27-8 Apoptosis NF-Κb Proteases/Proteasome Ubiquitination Proteasome NF-κB Inhibitor CEP 18770 CEP-18770 anti-cancer Nuclear factor-κB Nuclear factor-kappaB chymotrypsin-like antiangiogenic inhibit CEP18770 inhibitor

本ウェブサイトに掲載されている製品は全て研究用試薬です。研究目的以外の用途にはご使用できません。

Delanzomib

保存条件

溶解度情報

参考文献

引用文献

関連化合物ライブラリー

関連製品

投与量変換

In vivo投与量計算 (透明溶液)

計算器

モル度計算機では以下の計算が可能です

溶液を作るのに必要な希釈率の計算

バイアルを再構成するのに必要な溶媒の量を計算する.

化合物の化学式を入力して、そのモル質量や元素組成を計算します

技術サポート

Keywords