Home Apoptosis Bcl-2 inhibitor AZD5991 For research use only.

AZD5991

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.

AZD5991 Chemical Structure

AZD5991 Chemical Structure

CAS: 2143010-83-5

Selleck's AZD5991 has been cited by 16 publications

Purity & Quality Control

Batch: S864301 DMSO] 100 mg/mL] false] Water] Insoluble] false] Ethanol] Insoluble] false Purity: 98.41%
98.41

Products often used together with AZD5991

Bortezomib

AZD5991 and Bortezomib show potent antitumor activity in vivo with complete tumor regression in several models of multiple myeloma and acute myeloid leukemia.

Tron AE, et al. Nature communications 9.1 (2018): 5341.

Venetoclax (ABT-199)

AZD5991 and Venetoclax show potent antitumor activity in vivo with complete tumor regression in several models of multiple myeloma and acute myeloid leukemia.

Tron AE, et al. Nature communications 9.1 (2018): 5341.

Telaglenastat (CB-839)

AZD5991 and Telaglenastat increase apoptosis rate and inhibit cell proliferation in HG-3 and MEC-1 cell lines.

Timofeeva N, et al. Front Oncol. 2023 May 9;13:1161254.

Selumetinib (AZD6244)

AZD5991 and Selumetinib overcome MEKi resistance in triple-negative breast cancer (TNBC).

Mughees M, et al. Cancer Res (2022) 82 (12_Supplement): 1793.

Capivasertib (AZD5363)

AZD5991 and Capivasertib cause a reduction of cell viability in PTEN-deficient BC cells.

Dunn S, et al. Oncogene. 2022 Nov;41(46):5046-5060.

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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
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].
Cell Research 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.
Experimental Result Images Methods Biomarkers Images PMID
Western blot BCL2 / BCL-w / BCL-XL / MCL1 / BIM / BMF / p-ERK1/2 / ERK1/2 / PARP / β-actin / GAPDH BCL-XL / MCL1 / BIM / BMF / p-ERK1/2 / ERK1/2 / PARP / β-actin Caspase 3 / cPARP / Bak Mcl-1 / Bcl-2 / Bcl-Xl / Bim / cCaspase3 / Vinculin MCL1 / NOXA/ Vinc 31727888
Growth inhibition assay Tumor Volume Tumor Volume Cell Viability Cell Viability 31727888
In Vivo
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].
Animal Research Animal Models Subcutaneous MOLP-8 tumors model (Female C.B.-17 SCID mice)
Dosages 10-100 mg/kg
Administration IV
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT03218683 Terminated Relapsed or Refractory Acute Myeloid Leukemia (AML) AstraZeneca August 2 2017 Phase 1

Chemical lnformation & Solubility

Molecular Weight 672.26 Formula

C35H34ClN5O3S2
CAS No. 2143010-83-5 SDF --
Smiles CC1=C2C(=NN1C)CSCC3=NN(C(=C3)CSC4=CC5=CC=CC=C5C(=C4)OCCCC6=C(N(C7=C6C=CC(=C27)Cl)C)C(=O)O)C
Storage (From the date of receipt) 3 years -20°C powder

In vitro
Batch:

DMSO : 100 mg/mL ( (148.75 mM)； Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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In vivo
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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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