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
In vivo (Add solvents to the product individually and in order)
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <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.)

Preparing Stock Solutions

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]. This compound 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. This compound is well tolerated by the mice with no significant weight loss observed. Some of solid tumour models shows sensitivity to this compound monotherapy, while many others are only killed when treated with a combination of this compound 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.

References

  • http://jxym.amegroups.com/article/view/4013
  • https://pubmed.ncbi.nlm.nih.gov/27760111/

Selleck's S63845 Has Been Cited by 137 Publications

Co-targeting of epigenetic regulators and BCL-XL improves efficacy of immune checkpoint blockade therapy in multiple solid tumors [ Mol Cancer, 2025, 24(1):154] PubMed: 40442785
Prolonging lung cancer response to EGFR inhibition by targeting the selective advantage of resistant cells [ Nat Commun, 2025, 16(1):7853] PubMed: 40846697
Myeloid EGFR deficiency accelerates recovery from AKI via macrophage efferocytosis and neutrophil apoptosis [ Nat Commun, 2025, 16(1):4563] PubMed: 40379634
Secondary Necrosis Following Caspase-Activation can Occur Independently of Gasdermin E [ Adv Sci (Weinh), 2025, 12(46):e07381] PubMed: 41185624
Synergistic activity of S63845 and parthenolide to overcome acquired resistance to MEK1/2 inhibitor in melanoma cells: Mechanisms and therapeutic potential [ Biomed Pharmacother, 2025, 188:118183] PubMed: 40424823
BH3 mimetics augment cytotoxic T cell killing of acute myeloid leukemia via mitochondrial apoptotic mechanism [ Cell Death Discov, 2025, 11(1):120] PubMed: 40140361
Mitochondrial priming and response to BH3 mimetics in "one-two punch" senogenic-senolytic strategies [ Cell Death Discov, 2025, 11(1):91] PubMed: 40055336
BDA-366 inhibits extra-nodal natural killer/T-cell lymphoma by inducing mitochondria damage through NF-κB pathway [ Biochem Pharmacol, 2025, S0006-2952(25)00712-9] PubMed: 41135664
Bcl‑xL‑specific BH3 mimetic A‑1331852 suppresses proliferation of fluorouracil‑resistant colorectal cancer cells by inducing apoptosis [ Oncol Rep, 2025, 53(2)26] PubMed: 39717947
Senolytic compounds reduce epigenetic age of blood samples in vitro [ NPJ Aging, 2025, 11(1):6] PubMed: 39905063

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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.