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Cat. No.: HY-189823

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XY-09-36

XY-09-36 is a HDAC8 PROTAC degrader with a DC₅₀ value of 30 nM (HEK 293T eGFP.HDAC8-IRES-mCherry reporter cells, 24 h). XY-09-36 binds HDAC8 and recruits VHL E3 ubiquitin ligase, inducing HDAC8 ubiquitination and proteasomal degradation; the IC₅₀ values of XY-09-36 against HDAC8 and HDAC6 are 2.03 μM and 7.21 μM, respectively. XY-09-36 selectively reduces the viability of STAG2-mutant Ewing sarcoma cells. XY-09-36 increases acetylated SMC3 levels. XY-09-36 can be used for research on Ewing sarcoma.
(Pink: HDAC8 ligand (HY-189824); Blue: VHL ligand (HY-125905); Black: linker (HY-W007469)).

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

CAS No.: 3025448-71-6
Formula: C₄₈H₅₈FN₇O₈S
Molecular Weight:912.08

Storage:

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

XY-09-36 Chemical Structure

CAS No.: 3025448-71-6

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Use of MCE Products

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

Biological Activity
- Description
- IC₅₀ & Target
- Cellular Effect
- In Vitro
Chemical Information
Purity & Documentation
References
Calculators
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Bioz

Biological Activity

Description

XY-09-36 is a HDAC8 PROTAC degrader with a DC₅₀ value of 30 nM (HEK 293T eGFP.HDAC8-IRES-mCherry reporter cells, 24 h). XY-09-36 binds HDAC8 and recruits VHL E3 ubiquitin ligase, inducing HDAC8 ubiquitination and proteasomal degradation; the IC₅₀ values of XY-09-36 against HDAC8 and HDAC6 are 2.03 μM and 7.21 μM, respectively. XY-09-36 selectively reduces the viability of STAG2-mutant Ewing sarcoma cells. XY-09-36 increases acetylated SMC3 levels. XY-09-36 can be used for research on Ewing sarcoma^[1]. (Pink: HDAC8 ligand (HY-189824); Blue: VHL ligand (HY-125905); Black: linker (HY-W007469)).

IC₅₀ & Target

^[1]

HDAC8

2.03 μM (IC₅₀)

HDAC6

7.21 μM (IC₅₀)

VHL

All PROTACs Isoforms :

All HDAC Isoforms :

Cellular Effect

Cell Line	Type	Value	Description	References
HEK-293T	DC₅₀	100 nM	HDAC8 degradation in HEK 293T eGFP.HDAC8-IRES-mCherry reporter cells after 5 h exposure to XY-09-36 measured by GFP/mCherry ratio. HDAC8 degradation in HEK 293T eGFP.HDAC8-IRES-mCherry reporter cells after 5 h exposure to XY-09-36 measured by GFP/mCherry ratio.	42677456
HEK-293T	DC₅₀	30 nM	HDAC8 degradation in HEK 293T eGFP.HDAC8-IRES-mCherry reporter cells after 24 h exposure to XY-09-36 measured by GFP/mCherry ratio. HDAC8 degradation in HEK 293T eGFP.HDAC8-IRES-mCherry reporter cells after 24 h exposure to XY-09-36 measured by GFP/mCherry ratio.	42677456
TC-32	DC₅₀	100 nM	HDAC8 degradation in STAG2-mutant Ewing sarcoma TC32 cells after XY-09-36 exposure estimated by Western blot. HDAC8 degradation in STAG2-mutant Ewing sarcoma TC32 cells after XY-09-36 exposure estimated by Western blot.	42677456

In Vitro

Anti-cancerOthers

Anti-cancer

XY-09-36 (250 nM-5 μM; 3-12 days) selectively reduces the viability of STAG2-mutant TC32 and SKES-1 Ewing cells and increases acSMC3, inducing acSMC3 at 250 nM^[1].

Others

XY-09-36 (5-24 h) degrades HDAC8 in HEK 293T eGFP.HDAC8-IRES-mCherry reporter cells, with a DC₅₀ value of 100 nM at 5 h and 30 nM at 24 h^[1].
XY-09-36 (10 nM-5 μM; 0.5-72 h) degrades HDAC8 in STAG2-mutant TC32 Ewing sarcoma cells with a cellular DC₅₀ of approximately 100 nM and increases acSMC3 without affecting other HDACs^[1].
XY-09-36 (1 μM; 6 h) selectively degrades HDAC8 in EW8 Ewing sarcoma cells without affecting other HDACs or HDAC8-related complexes^[1].
XY-09-36 (5 h) selectively downregulates HDAC8 in Kelly cells^[1].
XY-09-36 (1 μM)-induced HDAC8 degradation is rescued by proteasome, neddylation, HDAC8 ligand, and VHL ligand interventions, confirming a VHL/proteasome-dependent mechanism^[1].

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

Western Blot Analysis^[1]

Cell Line:

STAG2-mutant Ewing sarcoma TC32 cells
Concentration:

1 μM
Incubation Time:

0.5, 1, 2, 4, 6, 24, 48, 72 h
Result:

Time-course with 1 μM XY-09-36 revealed rapid and sustained degradation as early as 30 min, maintained through 24 h, with maximum degradation at 24 h; after 24 h, limited HDAC8 recovery was observed.
In TC32 immunoblotting, robust HDAC8 depletion was accompanied by increased acSMC3, whereas levels of other HDACs remained unaffected.

Cell Viability Assay^[1]

Cell Line:

STAG2-WT (A673, TC71) and STAG2-mut (TC32, SKES-1) Ewing cells
Concentration:

1 μM
Incubation Time:

12 days
Result:

Induced a modest but selective reduction in viability of STAG2-mut cells only.

Related Protocols :

Cell Viability Determination by MTT Colorimetric Assay

Chemical Information

CAS No. 3025448-71-6
Molecular Weight 912.08
Formula C₄₈H₅₈FN₇O₈S
SMILES

ONC(C1=CC2=C(C=CN2CCOC3=CC=C(CN(C)CCCOC4=CC(C5=C(C)N=CS5)=CC=C4CNC([C@H]6N(C([C@H](C(C)(C)C)NC(C7(F)CC7)=O)=O)C[C@H](O)C6)=O)C=C3)C=C1)=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]. Olaoye O, et al. Evaluation of HDAC8 as a Druggable Target in STAG2-Mutant Ewing Sarcoma. ACS chemical biology. 2026 Aug 26.

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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.

Bioz

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100 mg

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Biological Activity
- Description
- IC₅₀ & Target
- In Vitro
Chemical Information
Purity & Documentation
References

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XY-09-36

All PROTACs Isoforms

All HDAC Isoforms