Home Epigenetics Epigenetic Reader Domain inhibitor - Akt modulator - ERK modulator - Myc modulator - NF-κB inhibitor - Apoptosis related activator Alobresib (GS-5829)

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Alobresib (GS-5829) Epigenetic Reader Domain inhibitor

Cat.No.S8961

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

Chemical Structure

Molecular Weight: 437.49

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Quality Control

Batch: S896101 DMSO]87 mg/mL]false]Ethanol]11 mg/mL]false]Water]˂1 mg/mL]false Purity: 98.15%
98.15

Chemical Information, Storage & Stability

Molecular Weight 437.49 Formula

C26H23N5O2

 Storage (From the date of receipt) 3 years -20°C powder
CAS No. 1637771-14-2 -- Storage of Stock Solutions

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

Solubility

In vitro
Batch:

DMSO : 87 mg/mL (198.86 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 11 mg/mL

Water : ˂1 mg/mL

Molarity Calculator

Mass Concentration Volume Molecular Weight

In vivo
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Mechanism of Action

Targets/IC50/Ki
BET [1]
BLK [2]
Akt [2]
ERK1/2 [2]
MYC [2]
NF-κB [2]
In vitro

In-vitro experiments demonstrates high sensitivity of USC cell-lines to the exposure to this compound causing a dose-dependent decrease in the phosphorylated levels of c-Myc and a dose-dependent increase in caspase activation (apoptosis).[1] It 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 this agent also inhibits NF-κB signaling. Its-induced apoptosis results from an imbalance between positive (BIM) and negative regulators (BCL-XL) of the intrinsic apoptosis pathway.[2]
In vivo

Alobresib (GS-5829) has impressive activity against USC primary tumors as well as USC xenografts. Assessment of c-Myc expression in tumors exposed to this compound demonstrates down-regulation of both total and phospho c-Myc proteins. This chemical 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 this compound in USC patients harboring disease resistant to standard salvage chemotherapy are warranted.[1]
References

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

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

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