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Cat. No.: HY-161769

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HL435

HL435 is a BRD4 PROTAC degrader with DC₅₀ values of 11.9 nM (MDA-MB-231 cells) and 21.9 nM (MCF-7 cells), respectively. HL435 recruits the CRL4_DCAF11 E3 ubiquitin ligase complex to degrade BRD4 via the ubiquitin-proteasome system. HL435 induces cell cycle arrest and apoptosis (apoptosis) in cancer cells, downregulates the expression levels of cyclin D1 and cyclin B1, activates caspase-9, and induces PARP1 cleavage. HL435 exerts anti-tumor activity both in vitro and in mouse xenograft tumor models. HL435 can be used for the research of breast cancer and prostate cancer.
(Pink: BRD4 ligand (HY-78695); Blue: DCAF11 ligand (HY-161770); Black: linker (HY-W004640)).

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화학식: C₄₇H₄₈BrClF₃N₇O₇S
분자량:1027.34

보관:

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

Data Sheet (273 KB)

HL435 Chemical Structure

Amount: USD 0.00

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Use of MCE Products

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

Biological Activity
- 제품 설명
- IC₅₀ & Target
- In Vitro
- In Vivo
Chemical Information
순도&문서
References
Calculators
Help & FAQs
Classifications
Bioz

Biological Activity

제품 설명

HL435 is a BRD4 PROTAC degrader with DC₅₀ values of 11.9 nM (MDA-MB-231 cells) and 21.9 nM (MCF-7 cells), respectively. HL435 recruits the CRL4_DCAF11 E3 ubiquitin ligase complex to degrade BRD4 via the ubiquitin-proteasome system. HL435 induces cell cycle arrest and apoptosis (apoptosis) in cancer cells, downregulates the expression levels of cyclin D1 and cyclin B1, activates caspase-9, and induces PARP1 cleavage. HL435 exerts anti-tumor activity both in vitro and in mouse xenograft tumor models. HL435 can be used for the research of breast cancer and prostate cancer^[1]. (Pink: BRD4 ligand (HY-78695); Blue: DCAF11 ligand (HY-161770); Black: linker (HY-W004640)).

IC₅₀ & Target

^[1]

BRD4

Caspase 9

PARP-1

All PROTACs Isoforms :

All Epigenetic Reader Domain Isoforms :

All Caspase Isoforms :

All PARP Isoforms :

In Vitro

HL435 (H27) (0-1000 nM; 1-24 h) potently degrades BRD4 in MDA-MB-231 and MCF-7 cells, with DC₅₀ values of 11.9 nM and 21.9 nM, respectively, and a maximum degradation efficiency of >99%^[1].
HL435 (0-1.0 μM; 6 h) induces BRD4 degradation in MDA-MB-231 cells as well as WT-, ATG5^KO-, and ATG4B^KO-HeLa cells, and this process is independent of the autophagy-lysosome pathway^[1].
HL435 (0-2.0 μM; 6-8 h) induces BRD4 degradation in MDA-MB-231 and HEK293T cells via the ubiquitin-proteasome system, a process that requires activation of functional Cullin-RING E3 ligases^[1].
HL435 (50-5000 nM; 6-24 h) recruits the CRL4_DCAF11 E3 ubiquitin ligase complex, mediates proteasomal degradation of BRD4 in CRISPRi HEK293T cells, and forms a ternary complex with BRD4 and DCAF11^[1].
HL435 (48 h) potently inhibits the proliferation of 22RV1, MDA-MB-31, MCF7, and A549 cells, with IC₅₀ values of 8.7, 205, 378, and 1380 nM, respectively^[1].
HL435 (0.25-1.5 μM; 24 h) induces concentration-dependent cell cycle arrest in MCF-7 cells, blocking G0/G1 phase transition at low concentrations and G2/M phase transition at high concentrations^[1].
HL435 (0.5-1.0 μM; 24-36 h) potently induces apoptosis in MDA-MB-231 cells, with the apoptosis rate reaching 55.9% upon treatment with 1.0 μM for 36 h, and activates caspase-9 as well as induces PARP1 cleavage^[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 cells, MCF-7 cells
Concentration:

0, 0.1, 1, 10, 100, 500, 1000 nM (12 h treatment); 0.5 μM (time-course treatment)
Incubation Time:

12 h (concentration gradient); 1, 3, 6, 12, 24 h (0.5 μM treatment)
Result:

Achieved a maximum BRD4 degradation efficiency (D_max) >99% in both cell lines.
Exhibited DC₅₀ values of 11.9 nM in MDA-MB-231 cells and 21.9 nM in MCF-7 cells.
Induced detectable BRD4 degradation 1 hour after treatment, with protein half-lives of 1.38 hours in MDA-MB-231 cells and 1.31 hours in MCF-7 cells.

Cell Cycle Analysis^[1]

Cell Line:

human breast cancer MCF-7 cells, human breast cancer MDA-MB-231 cells
Concentration:

0.25, 0.5, 1.5 μM HL435 (MCF-7 flow cytometry); 1.0 μM HL435 (protein analysis)
Incubation Time:

24 h
Result:

Arrested MCF-7 cells at the G0/G1 phase at 0.25 μM, and at the G2/M phase at 1.5 μM.
Upregulated P53 and P21 levels and downregulated cyclin D1 and cyclin B1 levels in MCF-7 cells via western blot.

Apoptosis Analysis^[1]

Cell Line:

human breast cancer MDA-MB-231 cells
Concentration:

0.5, 1 μM HL435 (flow cytometry); 1 μM HL435 (protein analysis)
Incubation Time:

36 h (flow cytometry); 24 h (protein analysis)
Result:

Resulted in an apoptotic rate of 55.9% in MDA-MB-231 cells at 1.0 μM for 36 hours, which was over 20-fold more potent than JQ1.
Increased levels of cleaved caspase-9 and PARP1 via western blot.

In Vivo

HL435 (20 mg/kg; i.p.; daily, 6 days per week; 27 days) exhibits potent in vivo antitumor activity in a breast cancer xenograft model, achieving a 54.34% tumor growth inhibition rate, with good tolerability^[1].

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

Animal Model:

NOD-SCID (female, 6 to 7 weeks old, subcutaneous xenograft of MDA-MB-231 cells)^[1]
Dosage:

20 mg/kg
Administration:

i.p.; daily, 6 days per week; 27 days
Result:

Achieved a tumor growth inhibition rate (TGI) of 54.34%.
Reduced tumor weight by 51.12% compared to the vehicle group.
Showed body weight comparable to vehicle-treated mice, with no obvious toxicity observed.

Chemical Information

분자량 1027.34
화학식 C₄₇H₄₈BrClF₃N₇O₇S
SMILES

O=C(COC1=C(/C=C(C(C=CC(C(F)(F)F)=C2)=C2N3)\C3=O)C=C(Br)C=C1)NCCCOCCOCCOCCCNC(C[C@H]4C5=NN=C(C)N5C(SC(C)=C6C)=C6C(C7=CC=C(Cl)C=C7)=N4)=O
선적

Room temperature in continental US; may vary elsewhere.
보관

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

순도&문서

Select Batch:

Purity: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (273 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)

References

[1]. Wang Y, et al. Alkenyl oxindole is a novel PROTAC moiety that recruits the CRL4DCAF11 E3 ubiquitin ligase complex for targeted protein degradation. PLoS biology. 2024 May;22(5):e3002550. [Content Brief]

Calculators

몰농도 계산기

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

Mass Mass

Concentration Concentration

Volume Volume

Molecular Weight Molecular Weight

농도 희석 계산기

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

Concentration _(start) Concentration _(start)

Volume _(start) Volume _(start)

Concentration _(final) Concentration _(final)

Volume _(final) Volume _(final)

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

MOQ

Minimum order quantity

100 mg

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Amount: USD 0.00

Biological Activity
- 제품 설명
- IC₅₀ & Target
- In Vitro
- In Vivo
Chemical Information
순도&문서
References

상품명:
Cat. No.:
수량:
MCE Japan Authorized Agent:

상품명:
CAS No.:
Species:
Purity:
수량:

HL435

All PROTACs Isoforms

All Epigenetic Reader Domain Isoforms

All Caspase Isoforms

All PARP Isoforms