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Chemical Structure| 1668553-26-1 Chemical Structure| 1668553-26-1

Structure of A-1210477
CAS No.: 1668553-26-1

Chemical Structure| 1668553-26-1

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

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Product Details of A-1210477

CAS No. :1668553-26-1
Formula : C46H55N7O7S
M.W : 850.04
SMILES Code : O=C(C(N1CCN2CCOCC2)=C(CCCOC3=C4C=CC=CC4=CC=C3)C5=C1C(C6=C(COC7=CC=C(N8CCN(S(=O)(N(C)C)=O)CC8)C=C7)N(C)N=C6C)=CC=C5)O
MDL No. :MFCD28399118
InChI Key :XMVAWGSQPHFXKU-UHFFFAOYSA-N
Pubchem ID :66575373

Safety of A-1210477

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H320-H335
Precautionary Statements:P261-P280-P301+P312-P302+P352-P305+P351+P338

Isoform Comparison

Biological Activity

Target
  • Mcl-1

    MCL-1, IC50:26.2 nM

In Vitro:

Cell Line
Concentration Treated Time Description References
NHL cell lines 0, 5, 10, 15 μM 48 hours A-1210477 alone had minimal effect on cell viability but substantially sensitized resistant BCL2High NHL cell lines to navitoclax, and this synergy was driven primarily by BCL-2 inhibition. PMC4670945
MOLM13 cells 1–10 µM 48 hours A-1210477 dose-dependently induced apoptosis in MOLM13 cells. PMC6333829
MV4-11 cells 1–10 µM 48 hours A-1210477 dose-dependently induced apoptosis in MV4-11 cells. PMC6333829
OCI-AML5 cells 1–10 µM 48 hours A-1210477 had a weaker effect on inducing apoptosis in OCI-AML5 cells. PMC6333829
SKM1 cells 1–10 µM 48 hours A-1210477 had a weaker effect on inducing apoptosis in SKM1 cells. PMC6333829
H929 cells 10 μM 4 hours Reduced the amount of BIM co-iμMunoprecipitated with MCL-1, indicating that A-1210477 can disrupt the MCL-1-BIM complex. PMC4669759
HCC-1806 cells 0.1, 0.5, 1, 5, 10, 15, 20 μM 8 hours A-1210477 triggered MCL-1 elevation but did not affect NOXA protein levels. PMC4669759
H929 cells 0.1, 1, 10 μM 4 hours A-1210477 induced the release of cytochrome c, indicating its ability to initiate apoptosis in MCL-1-dependent cells. PMC4669759
H2110 cells 0.1, 1, 10 μM 72 hours A-1210477 kills MCL-1-dependent NSCLC cell line H2110. PMC4669759
H23 cells 0.1, 1, 10 μM 72 hours A-1210477 kills MCL-1-dependent NSCLC cell line H23. PMC4669759
A375 5 μM 48 hours To evaluate the efficacy of A-1210477 in combination with ABT-263 in killing melanoma cells. Results showed that the combination significantly reduced cell viability and induced apoptosis. PMC6125485
1205Lu 5 μM 48 hours To evaluate the efficacy of A-1210477 in combination with ABT-263 in killing melanoma cells. Results showed that the combination significantly reduced cell viability and induced apoptosis. PMC6125485
SK-MEL 28 5 μM 48 hours To evaluate the efficacy of A-1210477 in combination with ABT-263 in killing melanoma cells. Results showed that the combination significantly reduced cell viability and induced apoptosis. PMC6125485
HT144 5 μM 48 hours To evaluate the efficacy of A-1210477 in combination with ABT-263 in killing melanoma cells. Results showed that the combination significantly reduced cell viability and induced apoptosis. PMC6125485
WM852c 5 μM 48 hours To evaluate the efficacy of A-1210477 in combination with ABT-263 in killing melanoma cells. Results showed that the combination significantly reduced cell viability and induced apoptosis. PMC6125485
SK-MEL-2 5 μM 48 hours To evaluate the efficacy of A-1210477 in combination with ABT-263 in killing melanoma cells. Results showed that the combination significantly reduced cell viability and induced apoptosis. PMC6125485
Hs852T 5 μM 48 hours To evaluate the efficacy of A-1210477 in combination with ABT-263 in killing melanoma cells. Results showed that the combination significantly reduced cell viability and induced apoptosis. PMC6125485

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
SCID mice HT29 colon cancer xenograft model oral gavage 5 mg/kg Once a day for 3 days A-1210477 combined with cobimetinib significantly inhibited tumor growth and enhanced tumor cell apoptosis. PMC5136313

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

1.18mL

0.24mL

0.12mL

5.88mL

1.18mL

0.59mL

11.76mL

2.35mL

1.18mL

References

 

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