| Size | Price | |
|---|---|---|
| 5mg |
Purity: ≥98%
AZD-5991 S-enantiomer, the S-enantiomer of AZD-5991, is the less active enantiomer of AZD-5991. AZD-5991 S-enantiomer is a Mcl-1 inhibitor with an IC50 of 6.3 μM in FRET assay and a Kd of 0.98 μM in surface plasmon resonance (SPR) assay.
| ln Vitro |
AZD5991, a rationally designed macrocyclic molecule with high selectivity and affinity for Mcl-1 currently in clinical development. 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.[1]
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|---|---|
| ln 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. Based on these promising data, a Phase I clinical trial has been launched for evaluation of AZD5991 in patients with hematological malignancies[1]
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| Cell Assay |
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]
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| Animal Protocol |
AZD5991 was formulated in 30% 2-Hydroxypropyl-beta-cyclodextrin (HPBCD) at pH 9, bortezomib was formulated in saline solution (0.9% NaCl) and venetoclax in 10% ethanol, 30% polyethanolglycol (PEG) 400, 60% Phosal PG50. In mice, drugs were dosed intravenously in a volume of 5 mL kg-1 except for venetoclax that was dosed orally in a volume of 10 mL kg-1. One million MV4-11, five million MOLP-8, ten million NCI-H929 or five million OCI-AML3 cells were injected subcutaneously in the right flank of mice in a volume of 0.1 mL. In rats, AZD5991 was dosed intravenously in a volume of 10 mL kg-1. Ten million MV4-11 cells were injected subcutaneously in the right flank of rats in a volume of 0.1 mL.[1]
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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 |
672.259164333344
|
| Exact Mass |
671.179
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| CAS # |
2143061-82-7
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| Related CAS # |
AZD-5991;2143061-81-6;AZD-5991 Racemate;2143010-83-5
|
| PubChem CID |
131634760
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| Appearance |
White to off-white solid powder
|
| LogP |
6.8
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| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
7
|
| Rotatable Bond Count |
1
|
| Heavy Atom Count |
46
|
| Complexity |
1060
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| Defined Atom Stereocenter Count |
0
|
| SMILES |
ClC1=CC=C2C3CCCOC4C=C(C=C5C=CC=CC=45)SCC4=CC(CSCC5C(=C(C)N(C)N=5)C1=C2N(C)C=3C(=O)O)=NN4C
|
| 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)
|
| Chemical Name |
6-chloro-11,21,25,61-tetramethyl-11H,21H,61H-10-oxa-4,8-dithia-1(7,3)-indola-2(4,3),6(3,5)-dipyrazola-9(3,1)-naphthalenacyclotridecaphane-12-carboxylic acid
|
| Synonyms |
AZD-5991; AZD-5991 S-enantiomer; AZD 5991 S-enantiomer.
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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.
Hematological cell lines are preferentially sensitive to AZD5991. |
|---|
AZD5991 causes tumor regression in AML models.Nat Commun.2018 Dec 17;9(1):5341. |
AZD5991 exhibits potent anti-tumor efficacy in MM models.Nat Commun.2018 Dec 17;9(1):5341. |
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