| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| Other Sizes |
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Purity: ≥98%
| Targets |
Mcl-1 (Ki = 0.13 nM); Mcl-1 (IC50 = 0.7 nM)
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| ln Vitro |
AZD5991 is a potent and direct inhibitor of Mcl-1 with high selectivity versus other Bcl-2 family proteins. Inducing rapid apoptosis in cancer cells, most notably myeloma and acute myeloid leukemia (GI50 < 100 nM), AZD5991 binds directly to Mcl-1 and activates the Bak-dependent mitochondrial apoptotic pathway. AZD5991 kills hematological cells more frequently than solid tumor cells in a panel of cancer-derived cell lines[1][3].
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| ln Vivo |
After a single well-tolerated dose as monotherapy or in combination with bortezomib or venetoclax, AZD5991 exhibits significant antitumor activity in vivo with complete tumor regression in a number of models of multiple myeloma and acute myeloid leukemia. Cleavage of caspase-3 and PARP in these in vivo studies showed a strong correlation between AZD5991's cytotoxic activity and the activation of the mitochondrial apoptotic pathway[1].
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| Cell Assay |
MOLP-8 cells are treated with AZD5991 or DMSO ontrol for 30 min. AZD5991 or DMSO ontrol are applied to MOLP-8 cells. The samples are then centrifuged, and the pellet is resuspended in ice-cold lysis buffer and incubated for 20 minutes on ice while vortexing every five minutes. After samples have been centrifuged, the protein concentration has been determined. Prior to overnight incubation with anti-Mcl-1 antibody at 4 °C with rotation, samples are pre-cleared for 30 min using rotation and a 50% slurry of Protein A/G magnetic beads. The next step is to add Protein A/G magnetic beads, which are rotated for 1 hour at 4 °C. Each IP pellet is then given a 10% sample reducing agent addition and four PBS:lysis buffer washes before being subjected to a western blotting analysis.
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| Animal Protocol |
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| References | ||
| Additional Infomation |
AZD-5991 is under investigation in clinical trial NCT03218683 (Study of AZD5991 in Relapsed or Refractory Haematologic Malignancies.).
Mcl-1 Inhibitor AZD5991 is an inhibitor of induced myeloid leukemia cell differentiation protein (myeloid cell leukemia-1; Mcl-1; Bcl2-L-3), with potential pro-apoptotic and antineoplastic activities. Upon administration, AZD5991 binds to Mcl-1, thereby preventing the binding of Mcl-1 to and inactivation of certain pro-apoptotic proteins, and promoting apoptosis of cells overexpressing Mcl-1. Mcl-1, an anti-apoptotic protein belonging to the Bcl-2 family of proteins, is upregulated in cancer cells and promotes tumor cell survival. |
| Molecular Formula |
C35H34CLN5O3S2
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| Molecular Weight |
672.2592
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| Exact Mass |
671.179
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| CAS # |
2143010-83-5
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| Related CAS # |
AZD-5991;2143061-81-6;AZD-5991 (S-enantiomer);2143061-82-7
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| PubChem CID |
131634760
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| Appearance |
Typically exists as solid at room temperature
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| Density |
1.42±0.1 g/cm3(Predicted)
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| Boiling Point |
949.6±65.0 °C(Predicted)
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| LogP |
6.8
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
46
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| Complexity |
1060
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1C=CC2C3CCCOC4=CC(=CC5=CC=CC=C45)SCC4=CC(CSCC5C(=C(C)N(C)N=5)C=1C=2N(C)C=3C(=O)O)=NN4C
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| InChi Key |
KBQCEQAXHPIRTF-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C35H34ClN5O3S2/c1-20-31-29(38-40(20)3)19-45-17-22-15-23(41(4)37-22)18-46-24-14-21-8-5-6-9-25(21)30(16-24)44-13-7-10-26-27-11-12-28(36)32(31)33(27)39(2)34(26)35(42)43/h5-6,8-9,11-12,14-16H,7,10,13,17-19H2,1-4H3,(H,42,43)
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| Chemical Name |
17-chloro-5,13,14,22-tetramethyl-28-oxa-2,9-dithia-5,6,12,13,22-pentazaheptacyclo[27.7.1.14,7.011,15.016,21.020,24.030,35]octatriaconta-1(36),4(38),6,11,14,16,18,20,23,29(37),30,32,34-tridecaene-23-carboxylic acid
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| Synonyms |
AZD-5991 racemate; AZD5991; AZD 5991 racemate
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: ~100 mg/mL (~148.8 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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