Alobresib (GS-5829)

For research use only.

Catalog No.S8961

Alobresib (GS-5829) Chemical Structure

CAS No. 1637771-14-2

Alobresib (GS-5829) is a novel BET inhibitor that represents a highly effective therapeutics agent against recurrent/chemotherapy-resistant USC-overexpressing c-Myc. Alobresib (GS-5829) inhibits CLL cell proliferation and induces leukemia cell apoptosis through deregulation of key signaling pathways, such as BLK, AKT, ERK1/2, and MYC. Alobresib (GS-5829) also inhibits NF-κB signaling.

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Biological Activity

Description Alobresib (GS-5829) is a novel BET inhibitor that represents a highly effective therapeutics agent against recurrent/chemotherapy-resistant USC-overexpressing c-Myc. Alobresib (GS-5829) inhibits CLL cell proliferation and induces leukemia cell apoptosis through deregulation of key signaling pathways, such as BLK, AKT, ERK1/2, and MYC. Alobresib (GS-5829) also inhibits NF-κB signaling.
Targets
BET [1]
()
BLK [2]
()
Akt [2]
()
ERK1/2 [2]
()
MYC [2]
()
In vitro

In-vitro experiments demonstrates high sensitivity of USC cell-lines to the exposure to GS-5829 causing a dose-dependent decrease in the phosphorylated levels of c-Myc and a dose-dependent increase in caspase activation (apoptosis).[1] GS-5829 inhibits CLL cell proliferation and induces leukemia cell apoptosis through deregulation of key signaling pathways, such as BLK, AKT, ERK1/2, and MYC. IκBα modulation indicates that GS-5829 also inhibits NF-κB signaling. GS-5829-induced apoptosis results from an imbalance between positive (BIM) and negative regulators (BCL-XL) of the intrinsic apoptosis pathway.[2]

In vivo

GS-5829 has impressive activity against USC primary tumors as well as USC xenografts. Assessment of c-Myc expression in tumors exposed to the GS-5829 demonstrates down-regulation of both total and phospho c-Myc proteins. GS-5829 demonstrates excellent bioavailability after oral administration and is significantly more effective than JQ1 at the doses used in comparative experiments in vivo against USC xenografts. Clinical studies with GS-5829 in USC patients harboring disease resistant to standard salvage chemotherapy are warranted.[1]

Protocol

Cell Research:

[2]

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  • Cell lines: PBMC, MEC-1
  • Concentrations: 100 nM, 200 nM, 400 nM, 800 nM
  • Incubation Time: 72 h, 24 h
  • Method:

    TACS XTT cell proliferation/viability assay (Trevigen) is performed according to the manufacturer’s instructions on MEC-1 cells treated with GS-5829 or the BCR signaling inhibitors for 72 h. Half-maximal inhibitory concentrations (IC50) are calculated using Prism 6 or 7 based on technical triplicate measurements.


    (Only for Reference)
Animal Research:

[1]

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  • Animal Models: female CB17/lcrHsd-Prkd/scid mice bearing USC-ARK1 or USC-ARK2 xenograft
  • Dosages: 20 mg/kg, 10 mg/kg
  • Administration: Oral gavage
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 87 mg/mL (198.86 mM)
Ethanol 11 mg/mL (25.14 mM)
Water ˂1 mg/mL

* 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.

Chemical Information

Molecular Weight 437.49
Formula

C26H23N5O2

CAS No. 1637771-14-2
Storage powder
in solvent
Synonyms N/A
Smiles CC1=C(C(=NO1)C)C2=CC(=C3C(=C2)NC(=N3)C4CC4)C(C5=CC=CC=N5)(C6=CC=CC=N6)O

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Clinical Trial Information

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT02983604 Terminated Drug: GS-5829|Drug: Exemestane|Drug: Fulvestrant Advanced Estrogen Receptor Positive HER2- Breast Cancer Gilead Sciences January 10 2017 Phase 1|Phase 2
NCT02607228 Terminated Drug: Alobresib|Drug: Enzalutamide Metastatic Castrate-Resistant Prostate Cancer Gilead Sciences December 8 2015 Phase 1|Phase 2
NCT02392611 Completed Drug: Alobresib|Drug: Exemestane|Drug: Fulvestrant Solid Tumors and Lymphomas Gilead Sciences March 16 2015 Phase 1

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Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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Epigenetic Reader Domain Signaling Pathway Map

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID