A-1210477

Catalog No.S7790 Batch:S779002

Technical Data

Formula	C₄₆H₅₅N₇O₇S
Molecular Weight	850.04	CAS No.	1668553-26-1
Solubility (25°C)*	In vitro	DMSO	3 mg/mL (3.52 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

A-1210477 is a potent and selective MCL-1 inhibitor with K_i and IC50 of 0.454 nM and 26.2 nM, respectively, >100-fold selectivity over other Bcl-2 family members.

Targets

MCL-1 ^[1]
(Cell-free assay)

26.2 nM

In vitro

In H929 cells, A-1210477 binds to MCL-1 with high affinity and induces MCL-1 protein elevation. In H929, H2110, and H23 cells, A-1210477 induce the hallmarks of apoptosis, and inhibits MCL-1-dependent cell viability. A-1210477 also synergizes with navitoclax to kill a variety of cancer cell lines. ^[1] In SKBR3 cells, A-1210477 inhibits MCL-1–BIM interaction and induces classical features of apoptosis. ^[2] In addition, A-1210477 sensitizes non-Hodgkin's lymphoma cell lines to venetoclax (ABT-199). ^[3]

Protocol (from reference)

Kinase Assay:^{^[1]}	Binding affinity assays TR-FRET-binding affinity assays are performed for BCL-2, BCL-XL, and MCL-1 in 4.52 mM monobasic potassium phosphate, 15.48 mM dibasic potassium phosphate, 1 mM sodium EDTA, 0.05% Pluronic F-68 detergent, 50 mM sodium chloride, and 1 mM DTT (pH 7.5). For MCL-1 assays, GST-tagged MCL-1 (1 nM) is mixed with 100 nM f-Bak, 1 nM Tb-labeled anti-GST antibody, and compound at room temperature (RT) for 60 min. Fluorescence is measured on an Envision plate reader using a 340/35 nm excitation filter and 520/525 (f-Bak) and 495/510 nm (Tb-labeled anti-GST antibody) emission filters.
Cell Assay:^{^[1]}	Cell lines H929, H2110, and H23 cells Concentrations ~30 μM Incubation Time 48 h or 72 h Method Adherent cell lines are seeded at 50 000 cells per well in 96-well plates and treated for 48 h with compounds diluted in half-log steps starting at 30 μM and ending at 0.001 μM. Multiple myeloma cell lines were seeded at 15 000–20 000 cells per well and treated similarly. Effects on proliferation and viability were determined using CellTiter-Glo reagent according to the manufacturer’s instructions. IC50 values are determined by non-linear regression analysis of the concentration response data.

Kinase Assay:^{^[1]}

Binding affinity assays
TR-FRET-binding affinity assays are performed for BCL-2, BCL-XL, and MCL-1 in 4.52 mM monobasic potassium phosphate, 15.48 mM dibasic potassium phosphate, 1 mM sodium EDTA, 0.05% Pluronic F-68 detergent, 50 mM sodium chloride, and 1 mM DTT (pH 7.5). For MCL-1 assays, GST-tagged MCL-1 (1 nM) is mixed with 100 nM f-Bak, 1 nM Tb-labeled anti-GST antibody, and compound at room temperature (RT) for 60 min. Fluorescence is measured on an Envision plate reader using a 340/35 nm excitation filter and 520/525 (f-Bak) and 495/510 nm (Tb-labeled anti-GST antibody) emission filters.

Cell Assay:^{^[1]}

Cell lines
H929, H2110, and H23 cells
Concentrations
~30 μM
Incubation Time
48 h or 72 h
Method
Adherent cell lines are seeded at 50 000 cells per well in 96-well plates and treated for 48 h with compounds diluted in half-log steps starting at 30 μM and ending at 0.001 μM. Multiple myeloma cell lines were seeded at 15 000–20 000 cells per well and treated similarly. Effects on proliferation and viability were determined using CellTiter-Glo reagent according to the manufacturer’s instructions. IC50 values are determined by non-linear regression analysis of the concentration response data.

References

Customer Product Validation

: Data from [Data independently produced by , , Cancer Research, 2017, doi:10.1158/0008-5472]

: Data from [Data independently produced by , , Cell Death Dis, 2018, 9(9):907]

: Data from [Data independently produced by , , Cell Death Dis, 2016, 7(8):e2340. ]

: Data from [Data independently produced by , , Mol Cancer Ther, 2016, 15(12):3015-3027]

Selleck's A-1210477 has been cited by 52 publications

Targeting MCL-1 triggers DNA damage and an anti-proliferative response independent from apoptosis induction [ Cell Rep, 2023, 42(10):113176]	PubMed: 37773750
MCL1 Inhibition Overcomes the Aggressiveness Features of Triple-Negative Breast Cancer MDA-MB-231 Cells [ Int J Mol Sci, 2023, 24(13)11149]	PubMed: 37446326
MCL1 Inhibition Overcomes the Aggressiveness Features of Triple-Negative Breast Cancer MDA-MB-231 Cells [ Int J Mol Sci, 2023, 24(13)11149]	PubMed: 37446326
Serum level of apoptosis inhibitor of macrophage in dogs with histiocytic sarcoma and its association with the disease [ Vet Comp Oncol, 2023, 10.1111/vco.12897]	PubMed: 37088561
The multi-kinase inhibitor CG-806 exerts anti-cancer activity against acute myeloid leukemia by co-targeting FLT3, BTK, and Aurora kinases [ Res Sq, 2023, rs.3.rs-2570204]	PubMed: 36865133
Deregulation and epigenetic modification of BCL2-family genes cause resistance to venetoclax in hematologic malignancies [ Blood, 2022, blood.2021014304]	PubMed: 35704690
Novel roles of RTN4 and CLIMP-63 in regulating mitochondrial structure, bioenergetics and apoptosis [ Cell Death Dis, 2022, 13(5):436]	PubMed: 35508606
BH3-only protein expression determines hepatocellular carcinoma response to sorafenib-based treatment [ Cell Death Dis, 2021, 12(8):736]	PubMed: 34312366
Anti-Leukemic Properties of Aplysinopsin Derivative EE-84 Alone and Combined to BH3 Mimetic A-1210477 [ Mar Drugs, 2021, 19(6)285]	PubMed: 34063867
Cell cycle progression and transmitotic apoptosis resistance promote escape from extrinsic apoptosis [ J Cell Sci, 2021, 134(24)jcs258966]	PubMed: 34806752

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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.

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