1. Apoptosis
  2. Bcl-2 Family

AZD-5991 

Cat. No.: HY-101533
Handling Instructions

AZD-5991 is a potent and selective Mcl-1 inhibitor with an IC50 of 0.7 nM in FRET assay and a Kd of 0.17 nM in surface plasmon resonance (SPR) assay.

For research use only. We do not sell to patients.

AZD-5991 Chemical Structure

AZD-5991 Chemical Structure

CAS No. : 2143061-81-6

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Other Forms of AZD-5991:

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  • References

Description

AZD-5991 is a potent and selective Mcl-1 inhibitor with an IC50 of 0.7 nM in FRET assay and a Kd of 0.17 nM in surface plasmon resonance (SPR) assay.

IC50 & Target[1]

Mcl-1

0.7 nM (IC50)

Mcl-1

0.17 nM (Kd)

In Vitro

The selectivity of AZD-5991 is evaluated against pro-survival Bcl-2 family members using FRET assays. AZD-5991 is selective for Mcl-1 (IC50 0.72 nM, Ki=200 pM) vs. Bcl-2 (IC50=20 µM, Ki=6.8 µM), Bcl-xL (IC50=36 µM, Ki=18 µM), Bcl-w (IC50=49 µM, Ki=25 µM), and Bfl-1 (IC50=24 µM, Ki=12 µM). MOLP-8, MV4-11, and NCI-H23 cells are treated with AZD5991 (EC50=0.033, 0.024, 0.19 µM, respectively).AZD5991 binds directly to Mcl-1 and induces rapid apoptosis in cancer cells, most notably myeloma and acute myeloid leukemia, by activating the Bak-dependent mitochondrial apoptotic pathway. AZD5991 reduces the levels of Mcl-1 protein in AZD5991-sensitive but not in AZD5991-resistant MM cell lines further supporting the notion that activation of caspases by AZD5991 reduces Mcl-1 protein levels in AZD5991-sensitive cell lines[1].

In Vivo

A single intravenous (i.v.) dose of AZD5991 leads to a dose-dependent antitumor effect ranging from tumor growth inhibition (TGI) to tumor regression (TR). Ten days after treatment, AZD5991 shows 52% and 93% TGI (p<0.0001) at 10 and 30 mg/kg, respectively. At the same time point, AZD5991 at 60 mg/kg leads to 99% TR with no detectable tumors in 6 out of 7 mice, while complete TR is seen in 7 out of 7 mice in the 100 mg/kg dose group. AZD5991 also shows a dose-dependent duration of response with tumors in the 100 mg/kg group growing back later than those in the 60 mg/kg group. The magnitude of in vivo tumor efficacy is correlated with activation of caspase-3 in the tumor and concentration of AZD5991 in plasma. Treatment with AZD5991 was well tolerated at all dose levels with no significant body weight loss. A single dose of AZD5991 36 days after the first dose causes tumor regression in 4 out of 4 mice. In mice dosed with AZD5991 at 100 mg/kg on day 0 and day 1, tumors grow back later than those dosed with a single dose of AZD5991 at the same dose level[1].

Solvent & Solubility
In Vitro: 

10 mM in DMSO

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 1.4875 mL 7.4376 mL 14.8752 mL
5 mM 0.2975 mL 1.4875 mL 2.9750 mL
10 mM 0.1488 mL 0.7438 mL 1.4875 mL
*Please refer to the solubility information to select the appropriate solvent.
References
Animal Administration
[1]

Mice and Rats[1]
In mice, drugs (e.g., AZD5991; 10-100 mg/kg) are dosed intravenously in a volume of 5 mL/kg except for Venetoclax that is dosed orally in a volume of 10 mL/kg. One million MV4-11, five million MOLP-8, ten million NCI-H929 or five million OCI-AML3 cells are injected subcutaneously in the right flank of mice in a volume of 0.1 mL. In rats, AZD5991 (10-100 mg/kg) is dosed intravenously in a volume of 10 mL/kg. Ten million MV4-11 cells are injected subcutaneously in the right flank of rats in a volume of 0.1 mL. Tumor volumes (measured by caliper), animal body weight, and tumor condition are recorded twice weekly for the duration of the study. The tumor volume is calculated[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
Molecular Weight

672.26

Formula

C₃₅H₃₄ClN₅O₃S₂

CAS No.

2143061-81-6

SMILES

O=C(O)C1=C(CCCOC2=C(C=CC=C3)C3=CC4=C2)C5=C(N1C)C(C6=C(C)N(C)N=C6CSCC7=NN(C)C(CS4)=C7)=C(Cl)C=C5

Storage

Please store the product under the recommended conditions in the Certificate of Analysis.

Shipping

Room temperature in continental US; may vary elsewhere

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AZD-5991
Cat. No.:
HY-101533
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AZD-5991

Cat. No.: HY-101533