S63845

Catalog No.S8383 Batch:S838302

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)
		Ethanol	38 mg/mL (45.82 mM)
		Water	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.

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

Selleck's S63845 has been cited by 104 publications

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
Targeting MCL-1 triggers DNA damage and an anti-proliferative response independent from apoptosis induction [ Cell Rep, 2023, 42(10):113176]	PubMed: 37773750
Drug-repurposing screen on patient-derived organoids identifies therapy-induced vulnerability in KRAS-mutant colon cancer [ Cell Rep, 2023, 42(4):112324]	PubMed: 37000626
System analysis of Huang-Lian-Jie-Du-Tang and their key active ingredients for overcoming CML resistance by suppression of leukemia stem cells [ Phytomedicine, 2023, 117:154918]	PubMed: 37329755
STING agonism turns human T cells into interferon-producing cells but impedes their functionality [ EMBO Rep, 2023, e55536.]	PubMed: 36705069

RETURN POLICY
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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.