Art. -Nr.: HY-158345

PROTAC ATM degrader-1

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PROTAC ATM degrader-1 is a ATM PROTAC degrader with a K_D value of 1.17 nM. PROTAC ATM degrader-1 triggers DNA damage response, cell cycle arrest, and apoptosis in cancer cells via the ubiquitin-proteasome-dependent degradation pathway. PROTAC ATM degrader-1 can be used for research on colorectal cancer.
(Pink: ATM ligand (HY-185575); Blue: VHL ligand (HY-125845); Black: linker (HY-130544)).

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Reinheit: 98.01%
CAS. Nr.: 2821804-13-9
Formel: C₄₉H₅₅N₉O₆S
Molecular Weight:898.08

Speicherung:

Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month

PROTAC ATM degrader-1 Chemical Structure

CAS. Nr.: 2821804-13-9

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

Biologische Aktivität

Beschreibung

PROTAC ATM degrader-1 is a ATM PROTAC degrader with a K_D value of 1.17 nM. PROTAC ATM degrader-1 triggers DNA damage response, cell cycle arrest, and apoptosis in cancer cells via the ubiquitin-proteasome-dependent degradation pathway. PROTAC ATM degrader-1 can be used for research on colorectal cancer^[1]. (Pink: ATM ligand (HY-185575); Blue: VHL ligand (HY-125845); Black: linker (HY-130544)).

IC₅₀ & Target^[1]

ATM

1.17 nM (Kd)

VHL

Alle PROTACs Isoform-spezifische Produkte anzeigen :

Alle ATM/ATR Isoform-spezifische Produkte anzeigen :

Alle DNA/RNA Synthesis Isoform-spezifische Produkte anzeigen :

Cellular Effect

Cell Line	Type	Value	Description	References
A2780	IC₅₀	3.96 μM Compound: 9b	Cytotoxicity against human A2780 cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay Cytotoxicity against human A2780 cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay	[PMID: 38634707]
COLO 205	IC₅₀	5.11 μM Compound: 9b	Cytotoxicity against human COLO 205 cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay Cytotoxicity against human COLO 205 cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay	[PMID: 38634707]
HCT-116	IC₅₀	26.44 μM Compound: 9b	Cytotoxicity against human HCT-116 cells transfected with ATM shRNA assessed as reduction in cell viability measured after 48 hrs by MTT assay Cytotoxicity against human HCT-116 cells transfected with ATM shRNA assessed as reduction in cell viability measured after 48 hrs by MTT assay	[PMID: 38634707]
HCT-116	IC₅₀	5.82 μM Compound: 9b	Cytotoxicity against human HCT-116 cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay Cytotoxicity against human HCT-116 cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay	[PMID: 38634707]
HCT-116	IC₅₀	5.82 μM Compound: 9b	Cytotoxicity against human HCT-116 cells transfected with NC shRNA assessed as reduction in cell viability measured after 48 hrs by MTT assay Cytotoxicity against human HCT-116 cells transfected with NC shRNA assessed as reduction in cell viability measured after 48 hrs by MTT assay	[PMID: 38634707]
K562	IC₅₀	4.06 μM Compound: 9b	Cytotoxicity against human K562 cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay Cytotoxicity against human K562 cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay	[PMID: 38634707]
LoVo	IC₅₀	6.73 μM Compound: 9b	Cytotoxicity against human LoVo cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay Cytotoxicity against human LoVo cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay	[PMID: 38634707]
NCI-H358	IC₅₀	>20 μM Compound: 9b	Cytotoxicity against human NCI-H358 cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay Cytotoxicity against human NCI-H358 cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay	[PMID: 38634707]
RKO	IC₅₀	3.95 μM Compound: 9b	Cytotoxicity against human RKO cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay Cytotoxicity against human RKO cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay	[PMID: 38634707]
SW13	IC₅₀	3.31 μM Compound: 9b	Cytotoxicity against human SW13 cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay Cytotoxicity against human SW13 cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay	[PMID: 38634707]
SW480	IC₅₀	12.12 μM Compound: 9b	Cytotoxicity against human SW480 cells transfected with ATM shRNA assessed as reduction in cell viability measured after 48 hrs by MTT assay Cytotoxicity against human SW480 cells transfected with ATM shRNA assessed as reduction in cell viability measured after 48 hrs by MTT assay	[PMID: 38634707]
SW480	IC₅₀	2.59 μM Compound: 9b	Cytotoxicity against human SW480 cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay Cytotoxicity against human SW480 cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay	[PMID: 38634707]
SW480	IC₅₀	2.59 μM Compound: 9b	Cytotoxicity against human SW480 cells transfected with NC shRNA assessed as reduction in cell viability measured after 48 hrs by MTT assay Cytotoxicity against human SW480 cells transfected with NC shRNA assessed as reduction in cell viability measured after 48 hrs by MTT assay	[PMID: 38634707]
SW-620	IC₅₀	3.7 μM Compound: 9b	Cytotoxicity against human SW620 cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay Cytotoxicity against human SW620 cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay	[PMID: 38634707]
SW-620	IC₅₀	3.7 μM Compound: 9b	Cytotoxicity against human SW620 cells transfected with NC shRNA assessed as reduction in cell viability measured after 48 hrs by MTT assay Cytotoxicity against human SW620 cells transfected with NC shRNA assessed as reduction in cell viability measured after 48 hrs by MTT assay	[PMID: 38634707]
SW-620	IC₅₀	9.81 μM Compound: 9b	Cytotoxicity against human SW620 cells transfected with ATM shRNA assessed as reduction in cell viability measured after 48 hrs by MTT assay Cytotoxicity against human SW620 cells transfected with ATM shRNA assessed as reduction in cell viability measured after 48 hrs by MTT assay	[PMID: 38634707]

In Vitro

PROTAC ATM degrader-1 (Compound 9b) (0.01-50.0 μM; 48 h) exhibits low micromolar cytotoxicity against multiple human cancer cell lines, with highest potency in SW480 (IC₅₀ = 2.59 μM) and SW620 (IC₅₀ = 3.70 μM) colorectal cancer cells, and shows selective toxicity against cancer cells relative to normal HIEC-6 cells^[1].
PROTAC ATM degrader-1 (5-10 μM; 12 h) induces dose-dependent apoptosis in SW620 and SW480 colorectal cancer cells, with concurrent downregulation of BCL2 and upregulation of cleaved-caspase 3^[1].
PROTAC ATM degrader-1 (10 μM; 12 h) alters the proteomic profile of SW620 cells, causing significant downregulation of 326 proteins including ATM, and enriching pathways related to p53 signaling, cell cycle, and apoptosis^[1].
PROTAC ATM degrader-1 (5-10 μM; 12 h) induces dose-dependent G0/G1 phase arrest in SW620 colorectal cancer cells^[1].
PROTAC ATM degrader-1 (2.5-10 μM; 2-24 h) activates the DNA damage response in SW620 cells, inducing dose- and time-dependent increases in p-CHK2 (Thr68) and γ-H2AX^[1].
PROTAC ATM degrader-1 (0.09375-4.5 μM; 48 h) synergizes with the ATR inhibitor AZD6738 (HY-19323) to reduce cell viability in SW620 and SW480 colorectal cancer cells^[1].
PROTAC ATM degrader-1 (5 μM; 12 h) in combination with ATR inhibitor AZD6738 (1 μM) enhances DNA damage in SW620 and SW480 colorectal cancer cells, as shown by increased γ-H2AX foci^[1].

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

Apoptosis Analysis^[1]

Cell Line:

SW620, SW480 human colorectal cancer cells
Concentration:

5 and 10 μM (apoptosis assay); 1.25, 2.5, 5 and 10 μM (Western blot confirmation)
Incubation Time:

12 h
Result:

Induced dose-dependent apoptosis in both cell lines: In SW620 cells, apoptosis rates were ~15% (5 μM) and ~25% (10 μM); in SW480 cells, apoptosis rates were ~20% (5 μM) and ~30% (10 μM), with all conditions showing statistically significant increases compared to the DMSO control.
Downregulated anti-apoptotic BCL2 and upregulated cleaved-caspase 3 in SW620 and SW480 cells.

Cell Cycle Analysis^[1]

Cell Line:

SW620 human colorectal cancer cells
Concentration:

5 and 10 μM
Incubation Time:

12 h
Result:

Induced dose-dependent G0/G1 phase arrest in SW620 cells: The ratio of cells in G0/G1 phase increased from ~25% (DMSO) to ~35% (5 μM) and ~40% (10 μM), while the ratio of cells in G2-M phase decreased from ~15% (DMSO) to ~10% (5 μM) and ~5% (10 μM).

Western Blot Analysis^[1]

Cell Line:

SW620 human colorectal cancer cells
Concentration:

2.5, 5 and 10 μM (dose-dependent activation); 10 μM (time-dependent activation)
Incubation Time:

2, 4, 8, 12 and 24 h (time-dependent activation); 12 h (dose-dependent activation)
Result:

Induced dose- and time-dependent increases in p-CHK2 (Thr68) and γ-H2AX protein levels, key biomarkers of DNA double-strand breaks and DDR activation.

In Vivo

PROTAC ATM degrader-1 (Compound 9b) (15 mg/kg; i.p.; daily; 14 days) reduces SW620 colorectal tumor weight in nude mice, induces ATM degradation, enhances DNA damage and apoptosis, and synergizes with AZD6738 for improved efficacy^[1].

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

Animal Model:

BALB/c nude mice (female, 28−35 days old, 15 to 18 g, subcutaneously inoculated with SW620 cells)^[1]
Dosage:

15 mg/kg
Administration:

i.p.; daily; 14 days
Result:

Reduced tumor weight relative to the vehicle group.
Decreased ATM, BCL2, and pro-caspase 3 protein levels in tumor tissues.
Increased γ-H2AX and cleaved-caspase 3 levels in tumor tissues.
Showed no significant weight loss.
Increased γ-H2AX and cleaved-caspase 3 reactivity in tumor tissues via immunohistochemical staining.
Synergized with AZD6738 to further reduce tumor weight significantly compared to vehicle or monotherapy groups, and further increased γ-H2AX and cleaved-caspase 3 reactivity.

Chemical Information

CAS. Nr. 2821804-13-9
Appearance Solid
Molecular Weight 898.08
Formel C₄₉H₅₅N₉O₆S
Color Orange to reddish brown
SMILES

O=C([C@H]1N(C([C@@H](NC(CCCCCN2N=NC(CCCN3C(/C(C4=C3C=CC=C4)=C5C(NC6=C/5C=CC=C6)=O)=O)=C2)=O)C(C)(C)C)=O)C[C@H](O)C1)NCC7=CC=C(C8=C(C)N=CS8)C=C7
Versand

Room temperature in continental US; may vary elsewhere.

Speicherung

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

Lösungsmittel & Löslichkeit

In Vitro:

DMSO : 100 mg/mL (111.35 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

View the Complete Stock Solution Preparation Table

Preparing Stock Solutions

View the Complete Stock Solution Preparation Table

Concentration Solvent Mass

1 mg

5 mg

10 mg

Concentration

Solvent

Mass

1 mM

1.1135 mL

5.5674 mL

11.1349 mL

5 mM

0.2227 mL

1.1135 mL

2.2270 mL

10 mM

0.1113 mL

0.5567 mL

1.1135 mL

Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.

Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

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)}

Reinheit & Dokumentation

Select Batch:

Reinheit: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (281 KB)
SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 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]. Liu TT, et al. Discovery of a Meisoindigo-Derived PROTAC as the ATM Degrader: Revolutionizing Colorectal Cancer Therapy via Synthetic Lethality with ATR Inhibitors. J Med Chem. 2024;67(9):7620-7634. [Content Brief]

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.

Complete Stock Solution Preparation Table

Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg
DMSO	1 mM	1.1135 mL	5.5674 mL	11.1349 mL	27.8372 mL
	5 mM	0.2227 mL	1.1135 mL	2.2270 mL	5.5674 mL
	10 mM	0.1113 mL	0.5567 mL	1.1135 mL	2.7837 mL
	15 mM	0.0742 mL	0.3712 mL	0.7423 mL	1.8558 mL
	20 mM	0.0557 mL	0.2784 mL	0.5567 mL	1.3919 mL
	25 mM	0.0445 mL	0.2227 mL	0.4454 mL	1.1135 mL
	30 mM	0.0371 mL	0.1856 mL	0.3712 mL	0.9279 mL
	40 mM	0.0278 mL	0.1392 mL	0.2784 mL	0.6959 mL
	50 mM	0.0223 mL	0.1113 mL	0.2227 mL	0.5567 mL
	60 mM	0.0186 mL	0.0928 mL	0.1856 mL	0.4640 mL
	80 mM	0.0139 mL	0.0696 mL	0.1392 mL	0.3480 mL
	100 mM	0.0111 mL	0.0557 mL	0.1113 mL	0.2784 mL

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PROTAC ATM degrader-1

PROTAC Library

Alle PROTACs Isoform-spezifische Produkte anzeigen

Alle ATM/ATR Isoform-spezifische Produkte anzeigen

Alle DNA/RNA Synthesis Isoform-spezifische Produkte anzeigen

Biologische Aktivität

Chemical Information

Lösungsmittel & Löslichkeit

Reinheit & Dokumentation

Verweise

Help & FAQs

Complete Stock Solution Preparation Table

PROTAC ATM degrader-1 Related Classifications

HY-158345 Related Classifications