Mcl-1-IN-22
Mcl-1-IN-22 is a selective Mcl-1 inhibitor with a Ki of 0.015 μM. Mcl-1-IN-22 binds selectively to Mcl-1, disrupts the Mcl-1/Bak complex to release free Bak, triggering intrinsic apoptosis. Mcl-1-IN-22 can be used for the research of ovarian cancer.
For research use only. We do not sell to patients.
- Formula: C30H31Cl2N3O3
- Molecular Weight:552.49
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
- Protocols
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Description
IC50 & Target
[1]|
Mcl-1 0.015 μM (Ki) |
Bak |
In Vitro
Mcl-1-IN-22 (Compound N5) potently and selectively binds to purified Mcl-1 protein with a Ki of 0.015 μM, and exhibits minimal binding to Bcl-2, Bcl-xL, Bcl-w, and Bfl-1[1].
Mcl-1-IN-22 potently inhibits proliferation of Mcl-1-dependent A2780S, HO8910, H929, and MV411 cancer cells, has weak activity against ARH-77 cells, no activity against OVCAR3 cells, and low toxicity to normal HL-7702 and WI-38 cells[1].
Mcl-1-IN-22 (6 μM; 18 h) binds to intracellular Mcl-1 in A2780S cells, increasing the protein's thermal stability by raising its melting temperature by over 10 °C[1].
Mcl-1-IN-22 (3-6 μM) disrupts Bak-Mcl-1 complexes in A2780S cells in vitro in a concentration-dependent manner, increasing levels of free Bak[1].
Mcl-1-IN-22 (3-6 μM) induces apoptosis in A2780S cells in vitro in a concentration-dependent manner, with robust activation of caspase-9 and caspase-3 that exceeds the activity of AZD5991 at matching concentrations[1].
Mcl-1-IN-22 maintains potent antiproliferative activity against Cisplatin (HY-17394)-resistant A2780/CDDP cells, but its activity is dependent on Mcl-1 expression[1].
Mcl-1-IN-22 acts synergistically with Cisplatin and Paclitaxel (HY-B0015) to inhibit proliferation of A2780S and Cisplatin-resistant A2780/CDDP cells, with the strongest synergy observed with Paclitaxel in A2780/CDDP cells (CI = 0.4)[1].
Mcl-1-IN-22 (200 nM) does not exhibit significant binding affinity or inhibitory activity against HDAC 3, HDAC 4, HDAC 6, or HDAC 11 proteins[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Balb/c nude (female, 5 weeks old, 16−18 g, subcutaneous inoculation with A2780S cells)[1]
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Dosage:10 mg/kg; 30 mg/kg
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Administration:i.p.; daily; 14 days
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Result:Achieved 13.2% tumor growth inhibition (TGI) with a T/C value of 85.1%.
Achieved 35.2% TGI with a T/C value of 67.2%.
Caused no significant body weight loss.
Chemical Information
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Molecular Weight 552.49
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Formula C30H31Cl2N3O3
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SMILES
O=C(NO)C1=CC=CC(CN(C2)CCC3=C2N(CCCOC4=CC(C)=C(Cl)C(C)=C4)C5=C3C=C(Cl)C=C5)=C1
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocols
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Apoptosis
Apoptosis, also called programmed cell death, is generally characterized by distinct morphological characteristics.
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TUNEL staining for apoptotic DNA fragmentation
TUNEL staining detects DNA strand breaks by using terminal deoxynucleotidyl transferase to add labeled nucleotides to exposed 3′-OH DNA termini, generating either microscopic staining in fixed cells or tissue sections, or fluorescence/cytometric signal in cell suspensions. TUNEL positivity reflects DNA fragmentation but should not be interpreted alone as definitive apoptosis, because TUNEL can also label necrotic, autolytic, mechanically damaged, or DNA-repair-associated DNA breaks.
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Annexin V plus membrane-impermeant dye apoptosis staining
Annexin V-based apoptosis assays rely on the detection of phosphatidylserine (PS) externalization from the inner leaflet of the plasma membrane to the outer leaflet, an early biochemical hallmark of apoptosis. Fluorescently labeled Annexin V binds PS in a calcium-dependent manner, enabling identification of early apoptotic cells by flow cytometry or fluorescence microscopy. When combined with a membrane-impermeant DNA-binding dye (e. g. , propidium iodide), this approach allows discrimination between viable (Annexin V−/dye−), early apoptotic (Annexin V+/dye−), and late apoptotic or necrotic (Annexin V+/dye+) cell populations by assessing membrane integrity and PS exposure.
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Apoptosis Solutions
Apoptosis is a regulated, generally non-lytic cell-death pathway that removes unwanted, damaged, infected, or abnormal cells through coordinated morphological changes, caspase activation, DNA fragmentation, and membrane remodeling. The intrinsic apoptosis pathway is controlled mainly by mitochondrial outer membrane permeabilization, BCL-2 family proteins, cytochrome c release, apoptosome formation, caspase-9 activation, and downstream executioner caspase-3/7 activation. The extrinsic apoptosis pathway is initiated by death receptors such as Fas, TNFR, and TRAIL receptors, which recruit adaptor proteins and activate caspase-8 before engaging executioner caspases or mitochondrial amplification through BID cleavage. Apoptosis is linked to many phenotypes, including cancer cell killing, tissue homeostasis, immune regulation, neurodegeneration, infection response, and treatment-induced cytotoxicity; unresolved questions include how apoptosis interacts with necroptosis, pyroptosis, ferroptos
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Mcl-1-IN-22 Related Classifications
HY-183601 Related Classifications
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