AZD5991

Catalog No.S8643 Batch:S864301

Technical Data

Formula

C₃₅H₃₄ClN₅O₃S₂

Molecular Weight

672.26

CAS No.

2143010-83-5

Solubility (25°C)*

In vitro

DMSO

100 mg/mL (148.75 mM)

Water

Insoluble

Ethanol

Insoluble

In vivo (Add solvents to the product individually and in order)

Clear solution

5%DMSO 1 40%PEG300 2 5%Tween80 3 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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description

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.

Targets

Mcl-1 ^[2] (Cell-free assay)	Mcl-1 ^[1] (Cell-free assay)
0.13 nM(Ki)	0.7 nM

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].

Protocol (from reference)

Cell Assay:^{^[1]}	Cell lines MOLP-8 cells Concentrations 0-500 nM Incubation Time 30 min Method 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.
Animal Study:^{^[1]}	Animal Models Subcutaneous MOLP-8 tumors model (Female C.B.-17 SCID mice) Dosages 10-100 mg/kg Administration IV

Cell Assay:^{^[1]}

Cell lines
MOLP-8 cells
Concentrations
0-500 nM
Incubation Time
30 min
Method
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.

Animal Study:^{^[1]}

Animal Models
Subcutaneous MOLP-8 tumors model (Female C.B.-17 SCID mice)
Dosages
10-100 mg/kg
Administration
IV

References

Selleck's AZD5991 has been cited by 17 publications

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

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.