PROTAC ATR degrader-2

Name: PROTAC ATR degrader-2
Brand: MedChemExpress
SKU: HY-161615
Rating: 4.5 (0 reviews)

Cat. No.: HY-161615 Pureza: 99.73%: Ficha de datos
COA

SDS
Instrucciones de manejo
FAQs
Technical Support

PROTAC ATR degrader-2 is a selective ATR PROTAC degrader. PROTAC ATR degrader-2 degrades ATR in acute myeloid leukemia (AML) cells MV-4-11 and MOLM-13, with DC₅₀ values of 22.9 nM and 34.5 nM, respectively. PROTAC ATR degrader-2 has an IC₅₀ of 29.6 nM against ATR, and its IC₅₀ values against ATM and PI3K are both greater than 2000 nM. PROTAC ATR degrader-2 induces apoptosis, DNA damage, and upregulates p53 expression. PROTAC ATR degrader-2 inhibits cancer cell proliferation through the kinase-independent function of ATR protein. PROTAC ATR degrader-2 is applicable to research related to acute myeloid leukemia.
(Pink: ATR ligand (HY-161616); Blue: Cereblon ligand (HY-A0003); Black: linker (HY-43538)).

Para uso exclusivo en investigación. No vendemos a pacientes.

PROTAC ATR degrader-2 Estructura química

No. CAS : 3010273-12-5

Tamaño	Stock	Cantidad
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO ready for reconstitution	En stock	Estimated Time of Arrival: December 31
Solution
10 mM * 1 mL in DMSO	En stock	Estimated Time of Arrival: December 31
Solid
5 mg	En stock	Estimated Time of Arrival: December 31
10 mg	En stock	Estimated Time of Arrival: December 31
25 mg	En stock	Estimated Time of Arrival: December 31
50 mg	En stock	Estimated Time of Arrival: December 31
100 mg	Obtener un presupuesto
200 mg	Obtener un presupuesto

or Consulta para venta a granel

* Seleccione Cantidad antes de agregar artículos.

This product is a controlled substance and not for sale in your territory.

Revisión del cliente

Based on 1 Customer Validation

Recomendaciones destacadas

•Related Screening Libraries:

•Related Small Molecules:

•Related Proteins:

Ver todos los productos específicos de isoformas PROTACs:

Ver todas las isoformas

von Hippel-Lindau (VHL) Cereblon MDM2 cIAP1

Ver todos los productos específicos de isoformas ATM/ATR:

Ver todas las isoformas

ATM ATR TRRAP

Actividad biológica
Pureza y Documentación
Referencias
Revisión del cliente

Descripciòn

PROTAC ATR degrader-2 is a selective ATR PROTAC degrader. PROTAC ATR degrader-2 degrades ATR in acute myeloid leukemia (AML) cells MV-4-11 and MOLM-13, with DC₅₀ values of 22.9 nM and 34.5 nM, respectively. PROTAC ATR degrader-2 has an IC₅₀ of 29.6 nM against ATR, and its IC₅₀ values against ATM and PI3K are both greater than 2000 nM. PROTAC ATR degrader-2 induces apoptosis, DNA damage, and upregulates p53 expression. PROTAC ATR degrader-2 inhibits cancer cell proliferation through the kinase-independent function of ATR protein. PROTAC ATR degrader-2 is applicable to research related to acute myeloid leukemia^[1]. (Pink: ATR ligand (HY-161616); Blue: Cereblon ligand (HY-A0003); Black: linker (HY-43538)).

IC₅₀ & Target^[1]

ATR

29.6 nM (IC₅₀)

ATR

22.9 nM (DC₅₀, MV-4-11)

ATR

34.5 nM (DC₅₀, MOLM-13)

In Vitro

PROTAC ATR degrader-2 (Compound 8i) (3-10000 nM; 12-24 h) potently degrades ATR in MV-4-11 cells, with 75.7% and 93.4% degradation at 100 nM and 500 nM (12 h). Under 24 h treatment conditions, the DC₅₀ values for MV-4-11 and MOLM-13 cells are 22.9 nM and 34.5 nM, respectively. and a DC₅₀ of 22.9 nM^[1].
PROTAC ATR degrader-2 potently inhibits the growth of multiple acute myeloid leukemia cell lines, with IC₅₀ values ranging from 0.108 μM to 1.287 μM^[1].
PROTAC ATR degrader-2 (0.3-1.2 μM; 24 h) does not induce cell cycle arrest in MV-4-11 or MOLM-13 acute myeloid leukemia cells^[1].
PROTAC ATR degrader-2 (0.5 μM; 24-96 h) potently induces time-dependent apoptosis in MV-4-11 and MOLM-13 cells, with sustained apoptotic signaling even after compound removal^[1].
PROTAC ATR degrader-2 (0.01-1 μM; 24-48 h) induces apoptosis in MV-4-11 and MOLM-13 cells by increasing p53 levels, modulating Bax/BCL-2 expression, activating caspase-mediated apoptotic signaling, and triggering extensive DNA damage, without upregulating the cell cycle arrest marker p21^[1].
PROTAC ATR degrader-2 (0.5 μM; 24 h) disrupts nuclear envelope integrity in MV-4-11 cells, leading to nuclear deformation and breakdown of nuclear membrane structure^[1].
PROTAC ATR degrader-2 (48-72 h) downregulates the PI3K-AKT signaling pathway in MV-4-11 and MOLM-13 cells by reducing p-PI3K and p-AKT levels, contributing to its potent apoptotic activity^[1].

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

Apoptosis Analysis^[1]

Cell Line:	MV-4-11 and MOLM-13 acute myeloid leukemia cells
Concentration:	0.5 μM
Incubation Time:	48 h, 72 h, 96 h
Result:	Induced 44%, 55%, and 75% apoptosis in MV-4-11 cells at 48, 72, and 96 h, respectively. Induced 20%, 72%, and 84% apoptosis in MOLM-13 cells at 48, 72, and 96 h, respectively. Induced ~50% apoptosis in MV-4-11 cells and ~30% apoptosis in MOLM-13 cells after 24 h treatment followed by 72 h culture without compound.

Western Blot Analysis^[1]

Cell Line:	MV-4-11 and MOLM-13 acute myeloid leukemia cells
Concentration:	0.01 μM; 0.1 μM; 0.2 μM; 0.5 μM; 1 μM
Incubation Time:	24 h (0.01-1 μM); 48 h (0-1 μM)
Result:	Significantly increased p53 protein levels, upregulated pro-apoptotic Bax, downregulated anti-apoptotic BCL-2, and had no effect on p21 levels (24 h treatment). Reduced p-ATR and p-CHK1 levels (24 h treatment). Significantly upregulated Cleaved-PARP1 and Cleaved-Caspase3 levels in a dose-dependent manner (48 h treatment). Significantly increased γ-H2AX levels in a dose-dependent manner (24 h treatment), indicating extensive DNA damage.

Parmacokinetics

Species	Dose	Route	C_max	T_1/2	T_max	CL	V_ss	MRT	AUC	Bioavailability
Mice^[1]	5 mg/kg	i.v.	2.3 ng/mL	2.77 h	0.083 h	62.6 L/h	5.56 L	1.47 h	1282 ng/L.h	/
Mice^[1]	5 mg/kg	i.p.	0.468 ng/mL	2.21 h	1 h	54.9 L/h	10.5 L	3.15 h	1407 ng/L.h	114 %

Peso molecular

743.81

Fòrmula

C₄₀H₄₁N₉O₆

No. CAS

3010273-12-5

Appearance

Solid

SMILES

O=C(C1=NC(C2=CC=C(C(N3CCN(CCCCC(NC4=CC=CC5=C4CN(C(CC6)C(NC6=O)=O)C5=O)=O)CC3)=O)C=C2)=CN=C1N)NC7=CC=CC=C7

Envío

Room temperature in continental US; may vary elsewhere.

Almacenamiento

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

Solvente y solubilidad

In Vitro:

DMSO : 100 mg/mL (134.44 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions

Concentration Solvent Mass	1 mg	5 mg	10 mg

1 mM	1.3444 mL	6.7221 mL	13.4443 mL
5 mM	0.2689 mL	1.3444 mL	2.6889 mL
10 mM	0.1344 mL	0.6722 mL	1.3444 mL

View the Complete Stock Solution Preparation Table

* 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.

Calculadora de molaridad
Calculadora de dilución

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

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

This equation is commonly abbreviated as: C₁V₁ = C₂V₂

Concentration _(start)

Volume _(start)

Concentration _(final)

Volume _(final)

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (3.36 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

DMSO +

Tween-80 +

Saline

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.

The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).

Calculation results:

Working solution concentration: mg/mL

Method for preparing stock solution: mg drug dissolved in μL DMSO (Stock solution concentration: mg/mL).

The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).

Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.

If the continuous dosing period exceeds half a month, please choose this protocol carefully.

Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.

Pureza y Documentación

Purity: 99.73%

Select Batch:

Ficha de datos (275 KB) SDS (251 KB)

COA (247 KB) HNMR (149 KB) RP-HPLC (168 KB) LCMS (109 KB)

Instrucciones de manejo (2659 KB)

Referencias

[1]. Wang Y, et al. Discovery of Selective and Potent ATR Degrader for Exploration its Kinase-Independent Functions in Acute Myeloid Leukemia Cells. Angew Chem Int Ed Engl. 2024;63(17):e202318568. [Content Brief]

Complete Stock Solution Preparation Table

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg

DMSO	1 mM	1.3444 mL	6.7221 mL	13.4443 mL	33.6107 mL
	5 mM	0.2689 mL	1.3444 mL	2.6889 mL	6.7221 mL
	10 mM	0.1344 mL	0.6722 mL	1.3444 mL	3.3611 mL
	15 mM	0.0896 mL	0.4481 mL	0.8963 mL	2.2407 mL
	20 mM	0.0672 mL	0.3361 mL	0.6722 mL	1.6805 mL
	25 mM	0.0538 mL	0.2689 mL	0.5378 mL	1.3444 mL
	30 mM	0.0448 mL	0.2241 mL	0.4481 mL	1.1204 mL
	40 mM	0.0336 mL	0.1681 mL	0.3361 mL	0.8403 mL
	50 mM	0.0269 mL	0.1344 mL	0.2689 mL	0.6722 mL
	60 mM	0.0224 mL	0.1120 mL	0.2241 mL	0.5602 mL
	80 mM	0.0168 mL	0.0840 mL	0.1681 mL	0.4201 mL
	100 mM	0.0134 mL	0.0672 mL	0.1344 mL	0.3361 mL