AZD5991

製品コードS8643 バッチS864301

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
化学式

C35H34ClN5O3S2
分子量 672.26 CAS No. 2143010-83-5
Solubility (25°C)* 体外 DMSO 100 mg/mL (148.75 mM)
Water Insoluble
Ethanol Insoluble
体内 （毎回新しく調製した物を用意してください）
Clear solution
5%DMSO 40%PEG300 5%Tween80 50%ddH2O
5.0mg/ml Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to make it clear; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
* <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 AZD5991 is a macrocyclic MCL-1 inhibitor with sub-nanomolar affinity for MCL-1 (Ki = 0.13 nM). The binding affinity of AZD5991 is about 25-fold lower for mouse Mcl-1 vs. human Mcl-1 but only four-fold lower for rat Mcl-1.
in vitro

AZD5991 is a potent and direct inhibitor of Mcl-1 with high selectivity versus other Bcl-2 family proteins. AZD5991 binds directly to Mcl-1 and induces rapid apoptosis in cancer cells, most notably myeloma and acute myeloid leukemia (GI50 < 100nM), by activating the Bak-dependent mitochondrial apoptotic pathway. In a panel of cancer-derived cell lines of hematological or solid tumor origin, AZD5991 preferentially kills hematological cells[1][3].
in vivo

AZD5991 shows potent antitumor activity in vivo with complete tumor regression in several models of multiple myeloma and acute myeloid leukemia after a single tolerated dose as monotherapy or in combination with bortezomib or venetoclax. In these in vivo studies, the cytotoxic activity of AZD5991 tightly correlates with induction of the mitochondrial apoptotic pathway as evidenced by cleavage of caspase-3 and PARP[1].

プロトコル(参考用のみ)

細胞アッセイ 細胞株 MOLP-8 cells
濃度 0-500 nM
反応時間 30 min
実験の流れ

MOLP-8 cells are treated with AZD5991 or DMSO ontrol for 30 min. Then samples are centrifuged and pellet resuspended in ice-cold lysis buffer and incubated for 20 min on ice with vortexing every 5 min. Next, samples are centrifuged and protein concentration was assessed. Samples are pre-cleared for 30 min using rotation at 4 °C with 50% slurry of Protein A/G magnetic beads followed by incubation with anti-Mcl-1 antibody overnight at 4 °C with rotation. Protein A/G magnetic beads are then added for 1 h at 4 °C with rotation. Beads are washed four times with lysis buffer / PBS (1:1), then 10% sample reducing agent is added to each IP pellet followed by western blotting analysis.
動物実験 動物モデル Subcutaneous MOLP-8 tumors model (Female C.B.-17 SCID mice)
投薬量 10-100 mg/kg
投与方法 IV

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：

Targeting MCL-1 triggers DNA damage and an anti-proliferative response independent from apoptosis induction [ Cell Rep, 2023, 42(10):113176] PubMed: 37773750
Obatoclax Rescues FUS-ALS Phenotypes in iPSC-Derived Neurons by Inducing Autophagy [ Cells, 2023, 12(18)2247] PubMed: 37759469
Obatoclax Rescues FUS-ALS Phenotypes in iPSC-Derived Neurons by Inducing Autophagy [ Cells, 2023, 10.3390/cells12182247] PubMed: 37759469
Computational modeling of DLBCL predicts response to BH3-mimetics [ NPJ Syst Biol Appl, 2023, 9(1):23] PubMed: 37280330
Efficacy of retreatment with polatuzumab vedotin in combination with rituximab in polatuzumab vedotin-resistant DLBCL models [ Leuk Lymphoma, 2023, 1-11.] PubMed: 37548343
Pivotal role of PIM2 kinase in plasmablast generation and plasma cell survival, opening new treatment options in myeloma [ Blood, 2022, blood.2021014011] PubMed: 35108359
CRISPR activation screen identifies BCL-2 proteins and B3GNT2 as drivers of cancer resistance to T cell-mediated cytotoxicity [ Nat Commun, 2022, 13(1):1606] PubMed: 35338135
Targeting cellular iron homeostasis with ironomycin in diffuse large B cell lymphoma [ Cancer Res, 2022, canres.0218.2021] PubMed: 35078814
Overcoming acquired resistance to third-generation EGFR inhibitors by targeting activation of intrinsic apoptotic pathway through Mcl-1 inhibition, Bax activation, or both [ Oncogene, 2022, 10.1038/s41388-022-02200-5] PubMed: 35102249
Venetoclax enhances the efficacy of therapeutic antibodies in B-cell malignancies by augmenting tumor cell phagocytosis [ Blood Adv, 2022, bloodadvances.2022007364] PubMed: 35820018

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。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。