Alobresib (GS-5829)

Catalog No.S8961

For research use only.

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.

Alobresib (GS-5829) Chemical Structure

CAS No. 1637771-14-2

Purity & Quality Control

Choose Selective Epigenetic Reader Domain Inhibitors

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]
()
Click to View More Targets
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 (from reference)

Cell Research:

[2]

  • 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]

  • 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 3 years -20°C powder
2 years -80°C in solvent
Smiles CC1=C(C(=NO1)C)C2=CC(=C3C(=C2)NC(=N3)C4CC4)C(C5=CC=CC=N5)(C6=CC=CC=N6)O

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg g μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Molarity Calculator

Mass Concentration Volume Molecular Weight

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

(data from https://clinicaltrials.gov, updated on 2022-01-17)

Tech Support

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.

Handling Instructions

Tel: +1-832-582-8158 Ext:3
If you have any other enquiries, please leave a message.

* Indicates a Required Field

Please enter your name.
Please enter your email. Please enter a valid email address.
Please write something to us.
Tags: buy Alobresib (GS-5829) | Alobresib (GS-5829) supplier | purchase Alobresib (GS-5829) | Alobresib (GS-5829) cost | Alobresib (GS-5829) manufacturer | order Alobresib (GS-5829) | Alobresib (GS-5829) distributor