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）
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution
5%DMSO 40%PEG300 5%Tween80 50%ddH2O

この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。

 5.000mg/ml (7.44mM) 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. This compound 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, this chemical 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 venetoclax. In these in vivo studies, the cytotoxic activity of this compound 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

参考

  • https://pubmed.ncbi.nlm.nih.gov/30559424/
  • https://www.ncbi.nlm.nih.gov/pubmed/?term=28735187
  • http://cancerres.aacrjournals.org/content/78/13_Supplement/302

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：

Ironomycin induces mantle cell lymphoma cell death by targeting iron metabolism addiction [ Theranostics, 2025, 15(7):2834-2851] PubMed: 40083931
Development of a robust BH3 drug toolkit for precision medicine in hematologic malignancies [ Theranostics, 2025, 15(12):5705-5718] PubMed: 40365276
Interplay of ferroptotic and apoptotic cell death and its modulation by BH3-mimetics [ Cell Death Differ, 2025, 10.1038/s41418-025-01514-7] PubMed: 40301648
Multidimensional, integrative profiling identifies BCL2L1 methylation as a predictor of MCL1 dependency in pediatric malignancies [ JCI Insight, 2025, 10(2)e184601] PubMed: 39846250
Targeting the WSB2-NOXA axis in cancer cells for enhanced sensitivity to BCL-2 family protein inhibitors [ Elife, 2025, 13RP98372] PubMed: 40699886
UGT8 mediated sulfatide synthesis modulates BAX localization and dictates apoptosis sensitivity of colorectal cancer [ Cell Death Differ, 2024, 10.1038/s41418-024-01418-y] PubMed: 39580596
MDM2 drives resistance to Osimertinib by contextually disrupting FBW7-mediated destruction of MCL-1 protein in EGFR mutant NSCLC [ J Exp Clin Cancer Res, 2024, 43(1):302] PubMed: 39543744
Mcl-1 mediates intrinsic resistance to RAF inhibitors in mutant BRAF papillary thyroid carcinoma [ Cell Death Discov, 2024, 10(1):175] PubMed: 38622136
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

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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