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Cat. No.: HY-182016

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PROTAC ATR degrader-3

PROTAC ATR degrader-3 is a potent CRBN-based ATR PROTAC degrader with a DC₅₀ of 127 nM. PROTAC ATR degrader-3 also degrades CHK1 with an DC₅₀ of 135 nM. PROTAC ATR degrader-3 inhibits cancer cells proliferation, migration and invasion, triggers apoptosis and induces S phase arrest and DNA damage. PROTAC ATR degrader-3 achieves tumor growth inhibition in LoVo xenograft mouse model without apparent toxicity. PROTAC ATR degrader-3 can be used for the research of colorectal cancer.
(Pink: ATR ligand (HY-182017); Blue: Cereblon ligand (HY-W077589A); Black: linker).

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

CAS No.: 3126270-11-6
Formula: C₄₁H₃₈N₈O₆
Molecular Weight:738.79

Storage:

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

PROTAC ATR degrader-3 Chemical Structure

CAS No.: 3126270-11-6

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Fluorescent Dye

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

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

Biological Activity

Description

PROTAC ATR degrader-3 is a potent CRBN-based ATR PROTAC degrader with a DC₅₀ of 127 nM. PROTAC ATR degrader-3 also degrades CHK1 with an DC₅₀ of 135 nM. PROTAC ATR degrader-3 inhibits cancer cells proliferation, migration and invasion, triggers apoptosis and induces S phase arrest and DNA damage. PROTAC ATR degrader-3 achieves tumor growth inhibition in LoVo xenograft mouse model without apparent toxicity. PROTAC ATR degrader-3 can be used for the research of colorectal cancer^[1]. (Pink: ATR ligand (HY-182017); Blue: Cereblon ligand (HY-W077589A); Black: linker).

IC₅₀ & Target^[1]

Cereblon

ATR

127 nM (DC₅₀)

Chk1

135 nM (DC₅₀)

Caspase 3

Bcl-2

All PROTACs Isoforms :

All ATM/ATR Isoforms :

All Checkpoint Kinase (Chk) Isoforms :

All DNA/RNA Synthesis Isoforms :

All Caspase Isoforms :

All Bcl-2 Family Isoforms :

In Vitro

PROTAC ATR degrader-3 (Compound A12) potently and selectively inhibits ATR kinase in cell-free assays with an IC₅₀ of 2.7 ± 0.5 nM, showing minimal activity against DNA-PK, PI3Kα, and ATM^[1].
PROTAC ATR degrader-3 (31 nM-5 μM; 8-72 h) induces potent, time- and concentration-dependent proteasome-mediated degradation of ATR in LoVo cells with a DC₅₀ of 127 nM and Dmax of 72% after 72 h^[1].
PROTAC ATR degrader-3 (72 h) induces potent degradation of ATR in SW480 (DC₅₀ = 140 nM, Dmax = 95%) and HCT116 (DC₅₀ = 48 nM, Dmax = 77%) colorectal cancer cells^[1].
PROTAC ATR degrader-3 (0-10 μM; 16-72 h) induces potent, concentration-dependent proteasome-mediated degradation of CHK1 in LoVo cells with a DC₅₀ of 135 nM and Dmax of 70% after 72 h^[1].
PROTAC ATR degrader-3 (72 h) induces degradation of CHK1 in SW480 (DC₅₀ = 426 nM, Dmax = 90%) and HCT116 (DC₅₀ = 95 nM, Dmax = 74%) colorectal cancer cells^[1].
PROTAC ATR degrader-3 (serial concentrations; 72 h) potently inhibits the proliferation of LoVo colorectal cancer cells with an IC₅₀ of 0.055 ± 0.010 μM, showing lower activity against SW480 (IC₅₀ = 0.37 μM), HCT116 (IC₅₀ = 2.774 μM), and normal NCM460 (IC₅₀ = 13.161 μM) cells^[1].
PROTAC ATR degrader-3 (250 nM; 48 h, with 2 μM MG132 co-treatment) enhances ATR polyubiquitination in LoVo cells, confirming ubiquitin-dependent proteasomal degradation^[1].
PROTAC ATR degrader-3 (0.5-2.0 μM; 48 h) induces S-phase cell cycle arrest in LoVo cells after 48 h of treatment, with maximum S-phase population of 38.05% at 1.0 μM^[1].
PROTAC ATR degrader-3 (0.5-4.0 μM; 48 h) dose-dependently induces apoptosis in LoVo cells by activation of caspase-mediated apoptotic pathways^[1].
PROTAC ATR degrader-3 (0.5-2.0 μM; 10 days) potently and dose-dependently suppresses colony formation of LoVo cells over 10 days^[1].
PROTAC ATR degrader-3 (0.5-2.0 μM; 24-48 h) dose-dependently inhibits the migration and invasion of LoVo cells^[1].
PROTAC ATR degrader-3 (0.5-4.0 μM; 24 h) induces dose-dependent DNA damage accumulation in LoVo cells, accompanied by increased γH2AX expression^[1].

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

Western Blot Analysis^[1]

Cell Line:

LoVo human colorectal cancer cells
Concentration:

31, 62, 125. 250, 500, 1000, 2000, 5000 nM
Incubation Time:

8, 16, 24, 48, 72 h
Result:

Induced 60 ± 5% ATR degradation at 0.1 μM and 78 ± 3% degradation at 0.5 μM after 72 h.
Achieved a DC₅₀ of 127 nM and maximum degradation (Dmax) of 72% after 72 h.
Induced significant ATR degradation at 250 nM by 48 h.
Blocked ATR degradation when cells were pre-treated with MG132 (HY-13259) or lenalidomide.

Western Blot Analysis^[1]

Cell Line:

LoVo human colorectal cancer cells
Concentration:

0-10000 nM (72 h); 1 μM (16 h, with 2 h pre-incubation with 2 μM MG132, 2 μM lenalidomide, or 2 μM C1); 0.5-4 μM (24 h)
Incubation Time:

16 h (with pre-treatment); 24 h; 72 h
Result:

Induced concentration-dependent CHK1 degradation with a DC₅₀ of 135 nM and Dmax of 70% after 72 h.
Blocked CHK1 degradation when cells were pre-treated with MG132 or lenalidomide.
Reduced CHK1 protein levels at concentrations ≥0.5 μM after 24 h.

Western Blot Analysis^[1]

Cell Line:

LoVo human colorectal cancer cells
Concentration:

250 nM (with 2 μM MG132 co-treatment)
Incubation Time:

48 h
Result:

Markedly enhanced polyubiquitination of ATR protein, as shown by increased ubiquitin signal in immunoprecipitated ATR samples.

Cell Cycle Analysis^[1]

Cell Line:

LoVo human colorectal cancer cells
Concentration:

0.5, 1.0, 2.0, 4.0 μM
Incubation Time:

48 h
Result:

Induced S-phase arrest: 35.30% of cells in S-phase at 0.5 μM, 38.05% at 1.0 μM, 37.65% at 2.0 μM, compared to 29.11% in control cells.
Reduced G0-G1 phase population to 53.69% (0.5 μM), 50.79% (1.0 μM), 51.80% (2.0 μM), compared to 58.66% in control cells.

Apoptosis Analysis^[1]

Cell Line:

LoVo human colorectal cancer cells
Concentration:

0.5-2.0 μM
Incubation Time:

48 h
Result:

Induced dose-dependent apoptosis.
Increased levels of cleaved PARP1 and cleaved Caspase-3 in a concentration-dependent manner.
Reduced Bcl-2 levels.

In Vivo

PROTAC ATR degrader-3 (Compound A12) (10-30 mg/kg; i.p.; twice daily; 32 days) demonstrates dose-dependent, significant suppression of LoVo colorectal cancer xenograft growth in nude mice, with a maximum TGI of 74% at 30 mg/kg, without adverse effects on body weight^[1].

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

Animal Model:

Nude mice with LoVo colorectal cancer xenograft (female, 7-8 weeks old)^[1]
Dosage:

10, 20, 30 mg/kg; 10 mg/kg (combination with Cetuximab)
Administration:

i.p.; twice daily; 32 days; i.v. (cetuximab, every 4 days)
Result:

Achieved 43% tumor growth inhibition (TGI) at 10 mg/kg monotherapy.
Achieved 57% TGI at 20 mg/kg monotherapy.
Achieved 74% TGI at 30 mg/kg monotherapy.
Achieved 81% TGI at 10 mg/kg in combination with Cetuximab (HY-P9905).
Caused no adverse effect on mouse body weight.
Downregulated ATR, p-ATR, CHK1, and p-CHK1 expression in tumor tissue.
Upregulated p-p53, p21, and γH2AX expression in tumor tissue.

Chemical Information

CAS No. 3126270-11-6
Molecular Weight 738.79
Formula C₄₁H₃₈N₈O₆
SMILES

C[C@@H]1COCCN1C2=C3C(CN(C3)C(C4=CC=C(C=C4)C(NCC5=CC=C6C(CN(C6=O)C7C(NC(CC7)=O)=O)=C5)=O)=O)=NC(C8=CC=CC9=C8C=CN9)=N2
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]. Mao N D, et al. Design and Synthesis of Pyrrolo [3, 4-d] pyrimidine-Based ATR Degraders for Effective Treatment of Colorectal Cancer in Mouse Model[J]. Journal of Medicinal Chemistry, 2026. [Content Brief]

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

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PROTAC ATR degrader-3

All PROTACs Isoforms

All ATM/ATR Isoforms

All Checkpoint Kinase (Chk) Isoforms

All DNA/RNA Synthesis Isoforms

All Caspase Isoforms

All Bcl-2 Family Isoforms

Biological Activity

Chemical Information

Purity & Documentation

References

Calculators

Help & FAQs

PROTAC ATR degrader-3 Related Classifications

HY-182016 Related Classifications