A-1210477

A-1210477 is a potent and selective inhibitor of MCL-1 with a Ki of 0.45 nM. A-1210477 specifically binds MCL-1 and promotes apoptosis of cancer cells in an MCL-1-dependent manner.

Product information

CAS Number: 1668553-26-1

Molecular Weight: 850.04

Formula: C46H55N7O7S

Chemical Name: 7-[5-({4-[4-(dimethylsulfamoyl)piperazin-1-yl]phenoxy}methyl)-1, 3-dimethyl-1H-pyrazol-4-yl]-1-[2-(morpholin-4-yl)ethyl]-3-[3-(naphthalen-1-yloxy)propyl]-1H-indole-2-carboxylic acid

Smiles: CN(C)S(=O)(=O)N1CCN(CC1)C1=CC=C(C=C1)OCC1=C(C2=CC=CC3=C2N(CCN2CCOCC2)C(C(O)=O)=C3CCCOC2=CC=CC3=CC=CC=C23)C(C)=NN1C

InChiKey: XMVAWGSQPHFXKU-UHFFFAOYSA-N

InChi: InChI=1S/C46H55N7O7S/c1-33-43(41(49(4)47-33)32-60-36-19-17-35(18-20-36)51-22-24-52(25-23-51)61(56,57)48(2)3)40-14-8-13-38-39(15-9-29-59-42-16-7-11-34-10-5-6-12-37(34)42)45(46(54)55)53(44(38)40)26-21-50-27-30-58-31-28-50/h5-8,10-14,16-20H,9,15,21-32H2,1-4H3,(H,54,55)

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO : 10 mg/mL (11.76 mM; Need ultrasonic)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥360 days if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

A-1210477 (10 μM) reduces the amount of BIM co-immunoprecipitated with MCL-1 antibody, and triggers MCL-1 elevation in a variety of cancer cell lines, including the breast cancer cell line HCC-1806. A-1210477 inhibits MCL-1-NOXA interactions with an IC50 of approximately 1 μM, while having no effect on BCL-2-BIM or BCL-XL-BCL-XS interactions. The NSCLC cell lines H2110 and H23 are sensitive to A-1210477 with cell viability IC50<10 μM, confirming that A-1210477 can kill MCL-1-dependent cell lines.

References:

1. Leverson JD, et al. Potent and selective small-molecule MCL-1 inhibitors demonstrate on-target cancer cell killing activity as single agents and in combination with ABT-263 (navitoclax). Cell Death Dis. 2015 Jan 15;6:e1590.
2. Qing Wang, et al. A-1210477, a selective MCL-1 inhibitor, overcomes ABT-737 resistance in AML. Oncol Lett. 2019 Nov;18(5):5481-5489.

Products are for research use only. Not for human use.