Art. -Nr.: HY-153414

GXF-111

GXF-111 is a BRD3 and BRD4-L PROTAC degrader. Its BD1 and BD2 Ki values against human BRD3 are 11.97 nM and 2.45 nM, respectively. The degradation activity of GXF-111 depends on its binding to BET proteins and Cereblon, as well as the involvement of a functional proteasome. The degradation selectivity of GXF-111 is mainly determined by differences in degradation kinetics and cell types. GXF-111 induces G₁ phase cell cycle arrest, downregulates c-Myc expression, upregulates p21 expression, and exhibits antiproliferative activity against a variety of cancer cell lines. GXF-111 can serve as a research tool for cancer-related studies.
(Pink: BRD3 and BRD4-L Target protein ligand; Blue: Cereblon ligand (HY-138793); Black: linker).

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Formel: C₄₂H₄₂ClN₇O₃
Molecular Weight:728.28

Speicherung:

Please store the product under the recommended conditions in the Certificate of Analysis.

Data Sheet (276 KB)

GXF-111 Chemical Structure

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Biologische Aktivität
- Beschreibung
- IC₅₀ & Target
- Cellular Effect
- In Vitro
Chemical Information
Reinheit & Dokumentation
Verweise
Calculators
Help & FAQs
Classifications
Bioz

Biologische Aktivität

Beschreibung

GXF-111 is a BRD3 and BRD4-L PROTAC degrader. Its BD1 and BD2 Ki values against human BRD3 are 11.97 nM and 2.45 nM, respectively. The degradation activity of GXF-111 depends on its binding to BET proteins and Cereblon, as well as the involvement of a functional proteasome. The degradation selectivity of GXF-111 is mainly determined by differences in degradation kinetics and cell types. GXF-111 induces G₁ phase cell cycle arrest, downregulates c-Myc expression, upregulates p21 expression, and exhibits antiproliferative activity against a variety of cancer cell lines. GXF-111 can serve as a research tool for cancer-related studies^[1]. (Pink: BRD3 and BRD4-L Target protein ligand; Blue: Cereblon ligand (HY-138793); Black: linker).

IC₅₀ & Target

BRD3 BD2

2.45 nM (Ki)

BRD3 BD1

11.97 nM (Ki)

BRD4-L

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Cellular Effect

Cell Line	Type	Value	Description	References
A549	IC₅₀	14.26 μM Compound: 24; GXF111	Antiproliferative activity against human A549 cells assessed as cell growth inhibition measured after 4 days by CCK-8 assay Antiproliferative activity against human A549 cells assessed as cell growth inhibition measured after 4 days by CCK-8 assay	[PMID: 37084596]
HeLa	IC₅₀	6.96 μM Compound: 24; GXF111	Antiproliferative activity against human HeLa cells assessed as cell growth inhibition measured after 4 days by CCK-8 assay Antiproliferative activity against human HeLa cells assessed as cell growth inhibition measured after 4 days by CCK-8 assay	[PMID: 37084596]
HepG2	IC₅₀	17.25 μM Compound: 24; GXF111	Antiproliferative activity against human HepG2 cells assessed as cell growth inhibition measured after 4 days by CCK-8 assay Antiproliferative activity against human HepG2 cells assessed as cell growth inhibition measured after 4 days by CCK-8 assay	[PMID: 37084596]
HGC-27	IC₅₀	2.35 μM Compound: 24; GXF111	Antiproliferative activity against human HGC-27 cells assessed as cell growth inhibition measured after 4 days by CCK-8 assay Antiproliferative activity against human HGC-27 cells assessed as cell growth inhibition measured after 4 days by CCK-8 assay	[PMID: 37084596]
MCF7	IC₅₀	0.23 μM Compound: 24; GXF111	Antiproliferative activity against human MCF7 cells assessed as cell growth inhibition measured after 4 days by CCK-8 assay Antiproliferative activity against human MCF7 cells assessed as cell growth inhibition measured after 4 days by CCK-8 assay	[PMID: 37084596]
MM1.S	IC₅₀	95.2 nM Compound: 24; GXF111	Antiproliferative activity against human MM1.S cells assessed as cell growth inhibition measured after 4 days by CellTitre-Glo assay Antiproliferative activity against human MM1.S cells assessed as cell growth inhibition measured after 4 days by CellTitre-Glo assay	[PMID: 37084596]
MV4-11	IC₅₀	6.31 nM Compound: 24; GXF111	Antiproliferative activity against human MV4-11 cells assessed as cell growth inhibition measured after 3 days by CellTitre-Glo assay Antiproliferative activity against human MV4-11 cells assessed as cell growth inhibition measured after 3 days by CellTitre-Glo assay	[PMID: 37084596]

In Vitro

GXF-111 (compound 24) binds to BRD3 BD2 with high affinity (K_i = 2.45 nM) and shows lower affinity for BRD3 BD1 (K_i = 11.97 nM), exhibiting approximately 5-fold selectivity for the BD2 domain of BRD3^[1].
GXF-111 (3-4) potently inhibits the growth of MV4-11 and MM.1S cells, with IC₅₀ values of 6.31 nM and 95.2 nM after 3-day and 4-day treatment, respectively^[1].
GXF-111 (for 4 days) inhibits the growth of MCF-7 (IC₅₀ = 0.23 μM), HGC-27 (IC₅₀ = 2.35 μM), A549 (IC₅₀ = 14.26 μM), HeLa (IC₅₀ = 6.96 μM) and HepG2 (IC₅₀ = 17.25 μM) cells^[1].
GXF-111 (0.1-30 nM; 24 h) selectively degrades BRD3 (1-3 nM) and BRD4-L in MM.1S cells without affecting BRD4-S, and only exerts a partial effect on BRD2 at higher doses; meanwhile, this compound regulates the expression of c-Myc and p21 without inducing significant apoptosis^[1].
GXF-111 (30 nM; 1-24 h) induces time-dependent selective degradation of BRD3 and BRD4-L in MM.1S, HGC-27 and MCF-7 cells. Compared with BRD2, the degradation of BRD3/BRD4-L initiates earlier, and GXF-111 exerts minimal effects on BRD4-S within 24 hours^[1].
GXF-111 (0.1-1000 nM; 24 h) selectively degrades BRD3 and BRD4-L (but not BRD2 or BRD4-S) in HGC-27, MCF-7, A549, HeLa and HepG2 cells, while it selectively degrades BRD4-L and BRD4-S in MV4-11 cells; its degradation efficacy varies among different cell lines^[1].
The degradation of BRD3 and BRD4-L in MM.1S cells induced by GXF-111 (30 nM; 4 h) depends on its binding to BET proteins, binding to Cereblon, and functional proteasome activity^[1].
GXF-111 (1-300 nM; 24 h) induces G₁-phase cell cycle arrest in MM.1S cells in a dose-dependent manner^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Western Blot Analysis^[1]

Cell Line:

MM.1S
Concentration:

0.1, 0.3, 1, 3, 10 and 30 nM
Incubation Time:

24 h
Result:

Dose-dependently depleted BRD3 and BRD4-L; BRD3 was depleted at 1-3 nM, while BRD2 was only partially depleted at 10 nM, and BRD4-S remained intact.
Decreased c-Myc expression and increased p21 expression, with minimal PARP cleavage detected.

Western Blot Analysis^[1]

Cell Line:

MM.1S, HGC-27, MCF-7
Concentration:

30 nM
Incubation Time:

1, 3, 6, 8 and 24 h
Result:

In MM.1S and MCF-7 cells, BRD3 and BRD4-L degradation began as early as 3-6 h, while BRD2 degradation onset was delayed until ~24 h.
In HGC-27 cells, BRD3 and BRD4-L degradation onset occurred after 8 h.
BRD4-S remained minimally degraded across all time points in all three cell lines.

Western Blot Analysis^[1]

Cell Line:

HGC-27, MCF-7, A549, HeLa, HepG2, MV4-11
Concentration:

0.1, 0.3, 1, 3, 10 and 30 nM (HGC-27, MV4-11); 1, 3, 10, 30, 100 and 300 nM (MCF-7); 3, 10, 30, 100, 300 and 1000 nM (A549); 1, 3, 10, 30, 100 and 300 (HeLa); 10, 30, 100, 300, 1000 and 3000 (HepG2)
Incubation Time:

24 h
Result:

In HGC-27, MCF-7, A549, HeLa, and HepG2 cells, BRD3 and BRD4-L were depleted dose-dependently, while BRD2 and BRD4-S remained intact.
In MV4-11 cells, BRD4-L and BRD4-S were selectively degraded over BRD2 and BRD3.
Degradation potency varied by cell line: 3-10 nM was sufficient for BRD3 degradation in HGC-27 and MCF-7, while 30-100 nM was required in A549, HeLa, and HepG2.

Western Blot Analysis^[1]

Cell Line:

MM.1S
Concentration:

30 nM
Incubation Time:

4 h
Result:

Degradation of BRD3 and BRD4-L by this compound was rescued by co-treatment with BY27 (HY-126325) (a BET binder) or Lenalidomide (HY-A0003) (a Cereblon binder).
The proteasome inhibitor MG132 (HY-13259) dose-dependently abolished this compound-induced degradation of BRD3 and BRD4-L.

Cell Cycle Analysis^[1]

Cell Line:

MM.1S
Concentration:

1-300 nM
Incubation Time:

24 h
Result:

Dose-dependently induced cell cycle arrest at the G1 phase of the cell cycle.

Chemical Information

Molecular Weight 728.28
Formel C₄₂H₄₂ClN₇O₃
SMILES

O=C1N(C2C(NC(CC2)=O)=O)CC3=C1C=CC=C3CCCCNCC4=CC=C(C5=CC=C6C(C(NC7=CC=C(Cl)C=C7)CCC8=NN=C(C)N86)=C5)C=C4
Versand

Room temperature in continental US; may vary elsewhere.
Speicherung

Please store the product under the recommended conditions in the Certificate of Analysis.

Reinheit & Dokumentation

Select Batch:

Reinheit: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (276 KB)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Handling Instructions (2659 KB)

Verweise

[1]. Yan Z, et al. Selective degradation of cellular BRD3 and BRD4-L promoted by PROTAC molecules in six cancer cell lines. European journal of medicinal chemistry. 2023 Jun 05;254:115381. [Content Brief]

Calculators

Molaritätsrechner

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass Mass

Konzentration Konzentration

Volumen Volumen

Molecular Weight Molecular Weight

Verdünnungsrechner

Konzentration _{(Stammlösung)} × Volumen _{(Stammlösung)} = Konzentration _{(Ziellösung)} × Volumen _{(Ziellösung)}

Konzentration _{(Stammlösung)} Konzentration _{(Stammlösung)}

Volumen _{(Stammlösung)} Volumen _{(Stammlösung)}

Konzentration _{(Ziellösung)} Konzentration _{(Ziellösung)}

Volumen _{(Ziellösung)} Volumen _{(Ziellösung)}

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

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GXF-111

Alle PROTACs Isoform-spezifische Produkte anzeigen

Alle Epigenetic Reader Domain Isoform-spezifische Produkte anzeigen

Biologische Aktivität

Chemical Information

Reinheit & Dokumentation

Verweise

Calculators

Help & FAQs

GXF-111 Related Classifications

HY-153414 Related Classifications