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Murizatoclax (AMG 397) 2245848-05-7

Murizatoclax (AMG 397) 2245848-05-7

CAS No.: 2245848-05-7

Murizatoclax (AMG 397) is a specific and orally bioactive myeloid leukemia 1 (MCL-1) inhibitor (antagonist) with a Ki of
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Murizatoclax (AMG 397) is a specific and orally bioactive myeloid leukemia 1 (MCL-1) inhibitor (antagonist) with a Ki of 15 pM. Murizatoclax competes with pro-apoptotic BCL-2 family members to bind to the BH3-binding groove of MCL1. Murizatoclax may be used in cancer research.

Physicochemical Properties


Molecular Formula C42H57CLN4O5S
Molecular Weight 765.443789243698
Exact Mass 764.373
CAS # 2245848-05-7
Related CAS # 2245848-05-7;
PubChem CID 138669688
Appearance White to off-white solid powder
LogP 7.3
Hydrogen Bond Donor Count 1
Hydrogen Bond Acceptor Count 8
Rotatable Bond Count 3
Heavy Atom Count 53
Complexity 1440
Defined Atom Stereocenter Count 7
SMILES

ClC1C=CC2=C(C=1)CCC[C@@]12COC2C=CC3C(NS([C@H](C)[C@@H](C)CC=C[C@](CN4CCN5CCCC[C@@H]5C4)([C@@H]4CC[C@H]4CN(C=2C=3)C1)OC)(=O)=O)=O |t:27|

InChi Key BJTFTQIBRVBSBH-VCQPVEJUSA-N
InChi Code

InChI=1S/C42H57ClN4O5S/c1-29-8-6-18-42(51-3,27-45-20-21-46-19-5-4-10-35(46)25-45)37-14-11-33(37)24-47-26-41(17-7-9-31-22-34(43)13-15-36(31)41)28-52-39-16-12-32(23-38(39)47)40(48)44-53(49,50)30(29)2/h6,12-13,15-16,18,22-23,29-30,33,35,37H,4-5,7-11,14,17,19-21,24-28H2,1-3H3,(H,44,48)/b18-6+/t29-,30+,33-,35+,37+,41-,42-/m0/s1
Chemical Name

(3'R,4S,6'R,7'R,8'E,11'S,12'R)-7'-[[(9aR)-1,3,4,6,7,8,9,9a-octahydropyrido[1,2-a]pyrazin-2-yl]methyl]-7-chloro-7'-methoxy-11',12'-dimethyl-13',13'-dioxospiro[2,3-dihydro-1H-naphthalene-4,22'-20-oxa-13λ6-thia-1,14-diazatetracyclo[14.7.2.03,6.019,24]pentacosa-8,16(25),17,19(24)-tetraene]-15'-one
HS Tariff Code 2934.99.9001
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)

Biological Activity


Targets MCL1 15 pM (Ki)
ln Vitro AMG 397 significantly reduces the interaction between MCL1 and BIM in OPM2 cells and, in less than an hour, causes observable increases in Caspase-3/7 activity[2].
ln Vivo In mice with OPM2 xenografts, murizatoclax (25–50 mg/kg; po once or twice weekly) significantly reduces tumors[2]. At doses of 10, 30, and 60 mg/kg, respectively, murizatoclax (10-60 mg/kg; po twice weekly) yields 47% MOLM-13 orthotopic tumor growth inhibition (TGI), 99% TGI, and 75% regression[2].
References

[1]. Targeting MCL-1 in cancer: current status and perspectives. J Hematol Oncol. 2021 Apr 21;14(1):67.

[2]. Abstract 6218: discovery and preclinical evaluation of AMG 397, a potent, selective and orally bioavailable MCL1 inhibitor. Cancer Res. 2020;80(16 Supplement):6218.

Additional Infomation Murizatoclax 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, MCL-1 inhibitor AMG 397 targets and binds to Mcl-1, thereby preventing the binding of Mcl-1 to and inactivation of certain pro-apoptotic proteins. This promotes apoptosis of cells overexpressing Mcl-1. Mcl-1, an anti-apoptotic protein belonging to the B-cell lymphoma 2 (Bcl-2) family of proteins, is upregulated in cancer cells and promotes tumor cell survival.

Solubility Data


Solubility (In Vitro) DMSO : 10 mg/mL (13.06 mM)
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
(e.g. IP/IV/IM/SC)
Injection Formulation 1: DMSO : Tween 80: Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution 50 μL Tween 80 850 μL Saline)
*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).
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)]
*Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO 100 μLPEG300 200 μL castor oil 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10: 10 : 80 (i.e. 100 μL Ethanol 100 μL Cremophor 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300:Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH 400 μLPEG300 50 μL Tween 80 450 μL 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).
Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 1.3064 mL 6.5322 mL 13.0644 mL
5 mM 0.2613 mL 1.3064 mL 2.6129 mL
10 mM 0.1306 mL 0.6532 mL 1.3064 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.