S63845

Catalog No.S8383 Batch:S838301

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Technical Data

Formula

C39H37ClF4N6O6S
Molecular Weight 829.26 CAS No. 1799633-27-4
Solubility (25°C)* In vitro DMSO 100 mg/mL (120.58 mM)
Water Insoluble
Ethanol Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description S63845 is a new, selective MCL-1 inhibitor with the Kd value of 0.19 nM and has no discernible binding to the other BCL-2 members, BCL-2 or BCL-XL.
Targets
human MCL-1 [1]
0.19 nM(Kd)
In vitro S63845 induces death of cancer cell lines with known reliance on MCL-1, displaying classical hallmarks of apoptosis that are dependent on caspases and BAX/BAK-mediated mitochondrial outer membrane permeabilisation. It has a 6 fold higher affinity for human MCL-1 over mouse MCL-1[1]. S63845 is effective against haematological cancer-derived cell lines in vitro and in vivo and also AML samples, but does not readily kill normal human haematopoietic progenitor cells[2].
In vivo In vivo, S63845 shows potent anti-tumour activity with an acceptable safety margin as a single agent in several cancers. S63845 is well tolerated by the mice with no significant weight loss observed. Some of solid tumour models shows sensitivity to S63845 monotherapy, while many others are only killed when treated with a combination of S63845 and inhibitors of oncogenic kinases[2].

Protocol (from reference)

Cell Assay:

[2]
  • Cell lines

    HeLa cells

  • Concentrations

    0.1, 0.3, 1, 3 μM

  • Incubation Time

    4 h

  • Method

    HeLa cells transduced with Flag–BCL-XL, Flag–BCL-2 or Flag–MCL1 expression constructs are treated for 4 h with increasing concentrations of S63845, before immunopreciptation using anti-FLAG antibody. Immunoprecipitates and total inputs are analysed by immunoblotting for the FLAG-tagged proteins as well as the associated BAK and BAX proteins.
Animal Study:

[2]
  • Animal Models

    C57BL/6 mice

  • Dosages

    25 mg/kg

  • Administration

    i.v.

Selleck's S63845 has been cited by 112 publications

Fatty acid synthase (FASN) is a tumor-cell-intrinsic metabolic checkpoint restricting T-cell immunity [ Cell Death Discov, 2024, 10(1):417] PubMed: 39349429
Initial AXL and MCL-1 inhibition contributes to abolishing lazertinib tolerance in EGFR-mutant lung cancer cells [ Cancer Sci, 2024, 10.1111/cas.16292] PubMed: 39039802
Defining a Water-Soluble Formulation of Arachidonic Acid as a Novel Ferroptosis Inducer in Cancer Cells [ Biomolecules, 2024, 14(5)555] PubMed: 38785962
Novel markers of MCL1 inhibitor sensitivity in triple-negative breast cancer cells [ J Biol Chem, 2024, 300(6):107375] PubMed: 38762181
Treatment with siRNAs is commonly associated with GPX4 up-regulation and target knockdown-independent sensitization to ferroptosis [ Sci Adv, 2024, 10(11):eadk7329] PubMed: 38489367
Gravitational and mechanical forces drive mitochondrial translation [ bioRxiv, 2024, 10.1101/2023.01.18.524628] PubMed: none
Executioner caspases restrict mitochondrial RNA-driven Type I IFN induction during chemotherapy-induced apoptosis [ Nat Commun, 2023, 14(1):1399] PubMed: 36918588
Executioner caspases restrict mitochondrial RNA-driven Type I IFN induction during chemotherapy-induced apoptosis [ Nat Commun, 2023, 14(1):1399] PubMed: 36918588
Co-targeting BCL-XL and BCL-2 by PROTAC 753B eliminates leukemia cells and enhances efficacy of chemotherapy by targeting senescent cells [ Haematologica, 2023, 108(10):2626-2638] PubMed: 37078252
Bcl-2 family inhibitors sensitize human cancer models to therapy [ Cell Death Dis, 2023, 14(7):441] PubMed: 37460459

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.