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Cat. No.: HY-187214

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PROTAC G9a degrader-1

PROTAC G9a degrader-1 is a selective and orally active G9a PROTAC degrader with a DC₅₀ of 1.29 μM. PROTAC G9a degrader-1 inhibits the NF-κB signaling pathway, suppresses the proliferation and migration of cancer cells, promotes apoptosis and cell cycle arrest, and reduces the expression level of H3K9me2. In in vivo models, PROTAC G9a degrader-1 alleviates skin inflammation, reduces epidermal hyperplasia, and decreases Ki67 expression. PROTAC G9a degrader-1 can be used for the research of triple-negative breast cancer and psoriasis.
(Pink: G9a ligand (HY-187215); Blue: Cereblon ligand (HY-103596); Black: linker).

For research use only. We do not sell to patients.

Formula: C₄₄H₆₀N₈O₇
Molecular Weight:813.00

Storage:

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

PROTAC G9a degrader-1 Chemical Structure

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Use of MCE Products

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Biological Activity
- Description
- IC₅₀ & Target
- In Vitro
- Parmacokinetics
- In Vivo
Chemical Information
Purity & Documentation
References
Calculators
Help & FAQs
Classifications
Bioz

Biological Activity

Description

PROTAC G9a degrader-1 is a selective and orally active G9a PROTAC degrader with a DC₅₀ of 1.29 μM. PROTAC G9a degrader-1 inhibits the NF-κB signaling pathway, suppresses the proliferation and migration of cancer cells, promotes apoptosis and cell cycle arrest, and reduces the expression level of H3K9me2. In in vivo models, PROTAC G9a degrader-1 alleviates skin inflammation, reduces epidermal hyperplasia, and decreases Ki67 expression. PROTAC G9a degrader-1 can be used for the research of triple-negative breast cancer and psoriasis^[1]. (Pink: G9a ligand (HY-187215); Blue: Cereblon ligand (HY-103596); Black: linker).

IC₅₀ & Target

^[1]

G9a

4.49 μM (IC₅₀)

G9a

1.29 μM (DC₅₀)

NF-κB

All PROTACs Isoforms :

All Histone Methyltransferase Isoforms :

All NF-κB Isoforms :

In Vitro

PROTAC G9a degrader-1 (Compound L4) potently inhibits G9a enzymatic activity in cell-free assays with an IC₅₀ of 4.49 μM; it potently suppresses the proliferation of MDA-MB-231 and Hs578T triple-negative breast cancer (TNBC) cells, with IC₅₀ values of 3.64 μM and 1.74 μM, respectively; and it forms a stable ternary complex with G9aSET and CRBNTBD via specific key interactions^[1].
PROTAC G9a degrader-1 (0.05-5 μM; 0-24 h) induces concentration- and time-dependent degradation of G9a via the CRBN-mediated ubiquitin-proteasome system in MDA-MB-231 triple-negative breast cancer (TNBC) cells, with a DC₅₀ of 1.29 μM. It also reduces H3K9me2 levels and exhibits selectivity toward GLP^[1].
PROTAC G9a degrader-1 (1 μM; 12 h) selectively downregulates G9a and ZFP91 in MDA-MB-231 triple-negative breast cancer (TNBC) cells, with minimal effects on closely related histone methyltransferases and most tested novel CRBN substrates^[1].
PROTAC G9a degrader-1 (1 μM) disrupts the expression of glucocorticoid receptor (GR)-responsive ENaCα gene in Dexamethasone (HY-14648)-stimulated MDA-MB-231 triple-negative breast cancer (TNBC) cells^[1].
PROTAC G9a degrader-1 (0.5-1 μM; 24-48 h) induces apoptosis, arrests MDA-MB-231 cells at the S phase, potently inhibits the migration of MDA-MB-231 and Hs578T triple-negative breast cancer (TNBC) cells at a concentration of 1 μM, and completely abolishes colony formation at 0.5 μM^[1].
PROTAC G9a degrader-1 (0-2 μM; 24 h) inhibits the proliferation of HaCaT keratinocytes with an IC₅₀ of 1.20 μM. It also induces concentration-dependent apoptosis and G2/M phase arrest, degrades G9a, reduces the level of H3K9me2, inhibits NF-κB pathway activation, and does not induce significant endoplasmic reticulum stress^[1].

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

Western Blot Analysis^[1]

Cell Line:

MDA-MB-231 triple-negative breast cancer (TNBC) cells
Concentration:

0.05, 0.1, 0.25, 0.5, 1, 1.25, 2.5, 5 μM (for concentration-dependent assay)
1 μM (for time-dependent assay)
1 μM (with 1 μM MG132 (HY-13259) or 10 μM Thalidomide (HY-14658) pre-treatment)
Incubation Time:

24 h (for concentration-dependent assay)
0, 4, 6, 8, 10, 12, 16, 24 h (for time-dependent assay)
24 h total (with pre-treatment)
Result:

Induced concentration-dependent G9a degradation with a DC₅₀ of 1.29 μM.
Induced time-dependent G9a degradation starting at 10 h, with near-complete degradation by 12 h and sustained effect through 24 h.
Reduced G9a protein levels and inhibited H3K9me2 expression at 1 μM.
Blocked G9a degradation was observed with MG132 or thalidomide pre-treatment, confirming a CRBN-mediated ubiquitin-proteasome system mechanism.
Increased G9a ubiquitination levels.
Showed selectivity for G9a over GLP, with GLP DC₅₀ > 5 μM and no appreciable GLP degradation at 1 μM over the tested time course.

Cell Migration Assay ^[1]

Cell Line:

MDA-MB-231 and Hs578T cells
Concentration:

0.5, 1 μM
Incubation Time:

24, 48 h
Result:

Reduced MDA-MB-231 cell migration to 12.4% and Hs578T cell migration to 22.6% at 1 μM for 48 h.

Apoptosis Analysis^[1]

Cell Line:

MDA-MB-231 and Hs578T cells, HaCaT cell
Concentration:

0.5, 1 μM (MDA-MB-231 and Hs578T cells)
0.5, 1, 1.75 μM (HaCaT cell)
Incubation Time:

24 h
Result:

Induced apoptosis in 27.53% of MDA-MB-231 cells and 18.37% of Hs578T cells at 1 μM.
Induced concentration-dependent apoptosis.

Cell Cycle Analysis^[1]

Cell Line:

HaCaT cells
Concentration:

0, 0.5, 1, 1.5 μM
Incubation Time:

24 h
Result:

Induced concentration-dependent G2/M-phase arrest.

Western Blot Analysis^[1]

Cell Line:

HaCaT cells
Concentration:

0, 0.5, 1, 2 μM
Incubation Time:

24 h
Result:

Degraded G9a and inhibited H3K9me2 expression in a concentration-dependent manner.
Reduced p-p65 expression and inhibited TNF-α-induced p65 nuclear translocation in a concentration-dependent manner.
No significant upregulation of ER stress markers GRP78 or ATF4 was observed.

Parmacokinetics

Species	Dose	Route	AUC_all	AUC_inf	T_1/2	CL	V_ss	MRT_{INF_obs}	T_max	F
Mice^[1]	1 mg/kg	i.v.	2404.8 ng·h/mL	2512 ng·h/mL	0.91 h	6.71 mL/min/kg	610.5 mL/kg	1.6 h	/	/
Mice^[1]	10 mg/kg	p.o.	8988.2 ng·h/mL	8798.4 ng·h/mL	1.86 h	/	/	2.89 h	1.10 h	29.10 %

In Vivo

PROTAC G9a degrader-1 (compound L4) (2%-4% topical ointment；8 consecutive days) dose-dependently alleviates Imiquimod (HY-B0180)-induced psoriasis-like erythema, scaling and epidermal thickening in Balb/c mice, relieves splenomegaly and decreases spleen index of model mice without obvious body weight loss, and exerts slighter systemic immune suppression than clobetasol^[1].

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

Animal Model:

Female BALB/c mice (5-6 weeks old) were topically administrated 5% imiquimod cream on shaved dorsal skin^[1]
Dosage:

2%, 4%
Administration:

Topical transdermal application; once daily; for 8 consecutive days
Result:

Alleviated IMQ-triggered erythema, scaling and epidermal thickening in a dose-dependent manner, and delivered stronger PASI score relief than 3% BIX01294 (HY-10587) and 0.02% Clobetasol (HY-W338819).
Displayed no evident mouse weight loss throughout treatment, which proved acceptable in vivo safety profile.
Mitigated IMQ-induced splenomegaly and cut down spleen index dose-dependently, with milder systemic immune suppression than clobetasol.
Showed remarkably alleviated epidermal hyperplasia and dermal inflammatory infiltration via skin lesion H&E staining.
Reduced Ki67, G9a and NF-κB p65 levels in lesional keratinocytes dose-dependently in IHC assays.
Exhibited no pathological lesions in heart, liver, spleen, lung and kidney on organ H&E staining.

Chemical Information

Molecular Weight 813.00
Formula C₄₄H₆₀N₈O₇
SMILES

O=C1N(C(CC2)C(NC2=O)=O)C(C3=C1C=CC=C3OCCCCCCCCCCN4CCC(NC5=C6C=C(OC)C(OC)=CC6=NC(N7CCN(C)CCC7)=N5)CC4)=O
Shipping

Room temperature in continental US; may vary elsewhere.
Storage

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

Purity & Documentation

Handling Instructions (2659 KB)

References

[1]. Liu M, et al. Discovery of a potent PROTAC targeting G9a suppresses proliferation of triple-negative breast cancer cells and psoriasis-like keratinocytes. European journal of medicinal chemistry. 2026 Jul 08;318:119131. [Content Brief]

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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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100 mg

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