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AZD5991 Bcl-2 inhibitor

Name: AZD5991
Brand: Selleck Chemicals
SKU: S8643
Availability: InStock
Rating: 5 (24 reviews)

Cat.No.S8643

AZD5991 is a macrocyclic MCL-1 inhibitor with sub-nanomolar affinity for MCL-1 (Ki = 0.13 nM). The binding affinity of this compound is about 25-fold lower for mouse Mcl-1 vs. human Mcl-1 but only four-fold lower for rat Mcl-1.

Chemical Structure

Molecular Weight: 672.26

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Quality Control

Batch: Purity: 99.78%

99.78

Products Often Used Together with AZD5991

Telaglenastat (CB-839)

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

AZD5363 (Capivasertib)

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

Related Targets	Caspase PD-1/PD-L1 Ferroptosis p53 Apoptosis related Synthetic Lethality STAT TNF-alpha Ras KRas
Other Bcl-2 Inhibitors	Navitoclax (ABT-263) S63845 ABT-737 Obatoclax Mesylate (GX15-070) A-1331852 A-1210477 TW-37 A-1155463 Dihydrochloride UMI-77 (R)-(-)-Gossypol (AT-101) acetic acid

Solubility

In vitro
Batch:

DMSO : 25 mg/mL (37.18 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
Mass value Mass unit	Concentration value Concentration unit	Volume value Volume unit	Molecular weight (g/mol)

Dilution Calculator Molecular Weight Calculator

In vivo batch selection In vivo Batch:
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 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	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.

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg

Average weight of animals: g

Dosing volume per animal: μL

Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO

% Tween 80

% ddH₂O

% DMSO

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Chemical Information, Storage & Stability

Molecular Weight	672.26	Formula	C₃₅H₃₄ClN₅O₃S₂	Storage (From the date of receipt)	3 years -20°C powder
CAS No.	2143010-83-5	--		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	N/A			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

Mechanism of Action

Targets/IC₅₀/Ki	Mcl-1 (Cell-free assay) 0.13 nM(Ki) Mcl-1 (Cell-free assay) 0.7 nM
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.
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.
References	[1] https://pubmed.ncbi.nlm.nih.gov/30559424/ [2] https://www.ncbi.nlm.nih.gov/pubmed/?term=28735187 [3] http://cancerres.aacrjournals.org/content/78/13_Supplement/302

Applications

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

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT03218683	Terminated	Relapsed or Refractory Acute Myeloid Leukemia (AML)	AstraZeneca	August 2 2017	Phase 1

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