Art. -Nr.: HY-153356

MRT-2359

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MRT-2359 is an orally active and selective GSPT1 molecular glue degrader, with a DC₅₀ of 5 nM. MRT-2359 induces CRBN/GSPT1 ternary complex formation to drive CRBN- and degron-dependent proteasomal GSPT1 degradation, with selectivity for wild-type GSPT1 over the GSPT1^G575N mutant. MRT-2359 disrupts protein translation, induces ribosome stalling, downregulates MYC family proteins and their transcriptional output, reduces proliferation, and induces apoptosis in cancer cells. MRT-2359 can be used for the research of non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), neuroendocrine lung cancer, high grade neuroendocrine cancers, diffuse large B-cell lymphoma, prostate cancer, and MYC-driven solid tumors.

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Reinheit: 99.91%
CAS. Nr.: 2803881-11-8
Formel: C₂₂H₁₇F₄N₃O₆
Molecular Weight:495.38

Speicherung:

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

MRT-2359 Chemical Structure

CAS. Nr.: 2803881-11-8

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Use of MCE Products

Fluorescent Dye

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

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

Biologische Aktivität

Beschreibung

IC₅₀ & Target^[1]

GSPT1

5 nM (DC₅₀)

In Vitro

MRT-2359 binds to CRBN in a cell-free HTRF assay with an IC₅₀ of 113 nM^[1].
MRT-2359 induces CRBN/GSPT1 ternary complex formation in a cell-free HTRF assay with an IC₅₀ of 7 nM, and this activity is ablated against the GSPT1^G575N mutant^[1].
MRT-2359 degrades GSPT1 in CAL51 cells with a DC₅₀ of 5 nM and 100% maximum degradation, and this activity is ablated in CAL51 cells expressing the GSPT1^G575N mutant^[1].
MRT-2359 (72 h) reduces CAL51 cell viability with an EC₅₀ of 150 nM, and this activity is ablated in CRISPR-mediated CRBN knockout CAL51 cells^[1].
MRT-2359 (>30000 nM) shows no inhibition of 7 CYP isoforms or hERG activity at concentrations >30000 nM^[1].
MRT-2359 (100 nM; 1 h) induces proximity between CRBN and GSPT1, leading to enrichment of GSPT1 and GSPT2 in CAL51 CRBN-Turbo ID cells^[1].
MRT-2359 (0.3-30 μM; 6 h) degrades GSPT1 but not common CRBN neosubstrates in MM1S and Kelly cells^[1].
MRT-2359 (72 h) reduces viability with preferential potency (median EC₅₀ ~50 nM) in NSCLC and SCLC cell lines with high N-MYC or L-MYC mRNA expression, compared to lower potency in cell lines with low MYC expression^[1].
MRT-2359 (24 h) degrades GSPT1 with >95% maximum degradation in NCI-H1155 (DC₅₀ = 2.1 nM), ABC-1 (DC₅₀ = 9.8 nM), NCI-H2023 (DC₅₀ = 28.8 nM), and NCI-H441 (DC₅₀ = 9.4 nM) NSCLC cell lines^[1].
MRT-2359 (0.03-0.3 μM; 6-48 h) degrades GSPT1 in both NCI-H1155 (N-MYC high) and NCI-H2023 (N-MYC low) NSCLC cell lines, and reduces N-MYC levels in a dose- and time-dependent manner in NCI-H1155 cells while N-MYC is undetectable in NCI-H2023 cells^[1].
MRT-2359 (0.1-1 μM; 6-24 h) represses MYC target gene expression in a dose- and time-dependent manner in NCI-H1155 (N-MYC high) NSCLC cells, while having no effect on MYC target gene expression in NCI-H2023 (N-MYC low) NSCLC cells^[1].
MRT-2359 shows profound, preferential antiproliferative activity in N-MYC and L-MYC high NSCLC and SCLC cell lines, with activity dependent on CRBN and the GSPT1 G-loop degron, and sole expression of N-MYC or L-MYC sensitizes initially resistant NSCLC cells to MRT-2359^[2].
MRT-2359 induces translational repression in N-MYC and L-MYC high NSCLC and SCLC cell lines, as evidenced by ribosome stalling at stop codons, increased monosomes, decreased polysomes, and changes in puromycilation assays^[2].
MRT-2359 reduces total N-MYC and L-MYC levels and downmodulates MYC target genes in N-MYC and L-MYC high NSCLC and SCLC cell lines, while driving robust GSPT1 degradation^[2].
MRT-2359 potently and selectively induces CRBN- and degron-dependent GSPT1 degradation, with preferential antiproliferative activity in Myc-driven NSCLC and SCLC lines (but not low N-Myc NSCLC lines) via translational repression, reduced Myc family protein levels, and downregulated Myc target gene expression^[3].
MRT-2359 exhibits preferential antiproliferative activity in NSCLC and SCLC cell lines with high N-MYC or L-MYC mRNA, and in sensitive prostate cancer cell line subgroups (androgen receptor-positive with high c-MYC, neuroendocrine with or without high N-MYC), while insensitive prostate cancer cell lines (androgen receptor/neuroendocrine-negative with low c-MYC) show minimal c-MYC reduction and no sensitivity^[4].
MRT-2359 induces 100% degradation of GSPT1 with a DC₅₀ of 5 nM in CAL-51 cells, with no activity against IKZF1, IKZF3, or CK1α^[5].
MRT-2359 exerts profound preferential antiproliferative activity in high N-Myc NSCLC cells and high L-Myc SCLC cells, linked to differential GSPT1 degradation, with minimal activity in low N-Myc/L-Myc cell lines^[5].

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

Western Blot Analysis^[1]

Cell Line:

MM1S multiple myeloma cells, Kelly neuroblastoma cells
Concentration:

0.3-30 μM
Incubation Time:

6 h
Result:

Degraded GSPT1 in both MM1S and Kelly cells at concentrations ≥0.3 μM.
Did not degrade the CRBN neosubstrates IKZF1, IKZF3, SALL4, ZFP91, or CK1a at any tested concentration.

Western Blot Analysis^[1]

Cell Line:

NCI-H1155 (N-MYC high) NSCLC cell lines, NCI-H2023 (N-MYC low) NSCLC cell lines
Concentration:

0.03-0.3 μM
Incubation Time:

6-48 h
Result:

In NCI-H1155 cells: degraded GSPT1 at both concentrations by 6 h, with sustained degradation through 48 h; reduced N-MYC levels in a dose- and time-dependent manner, with noticeable reduction by 24 h and sustained reduction through 48 h.
In NCI-H2023 cells: degraded GSPT1 at both concentrations by 6 h, with sustained degradation through 48 h; N-MYC was not detected at any time point or concentration.

In Vivo

MRT-2359 (3-10 mg/kg; p.o.; QD; QDx5) reduces tumor volume and degrades GSPT1 and N-MYC in N-MYC high NSCLC xenografts^[1].
MRT-2359 (10 mg/kg; p.o.; QD) demonstrates preferential anti-tumor activity in NSCLC PDX models with high L-MYC and/or N-MYC expression, with no significant activity in low-expression models^[1].
MRT-2359 (10 mg/kg; p.o.; QD) induces complete tumor growth inhibition in SCLC and neuroendocrine lung cancer PDX models^[1].
MRT-2359 (p.o.) induces complete intratumoral GSPT1 degradation, reduces N-Myc protein levels, and causes tumor regression in high N-Myc NSCLC xenografts and PDXs^[3].
MRT-2359 (p.o.) has limited or no activity in low N-Myc NSCLC xenograft models^[3].
MRT-2359 (10 mg/kg; once daily; 4 weeks) induces complete tumor regression of 22RV1 prostate cancer xenografts in immunocompromised mice with no subsequent tumor regrowth^[4].
MRT-2359 (10 mg/kg; once daily; 4 weeks) induces complete tumor regression of NCI-H660 neuroendocrine prostate cancer xenografts in immunocompromised mice with no subsequent tumor regrowth^[4].
MRT-2359 does not elicit a significant in vivo response against PC-3 prostate cancer xenografts in immunocompromised mice^[4].

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

Animal Model:

Immunocompromised mice^[1]
Dosage:

3 mg/kg; 10 mg/kg
Administration:

p.o.; QD; QDx5
Result:

Reduced tumor volume relative to vehicle control.
Induced sustained reduction in GSPT1 and N-MYC levels in tumors to ~0% relative to vehicle over 24 hours post-dose.

Animal Model:

Immunocompromised mice^[1]
Dosage:

10 mg/kg
Administration:

p.o.; QD
Result:

Achieved significantly higher tumor progression-free probability relative to vehicle control (p<0.0001) and marked tumor volume inhibition in 14 PDX models with high L-MYC and/or N-MYC expression.
Showed no statistically significant difference in tumor progression-free probability between MRT-2359 and vehicle control (p=0.14) in 19 PDX models with low L-MYC and N-MYC expression.

Clinical Trial

NCT Number	Sponsor	Condition	Start Date	Phase A549
NCT01329991	Plexxikon\|		2011-05	PHASE1

Chemical Information

CAS. Nr. 2803881-11-8
Appearance Solid
Molecular Weight 495.38
Formel C₂₂H₁₇F₄N₃O₆
Color White to off-white
SMILES

O=C(NC1=CC(OC(F)(F)F)=CC=C1F)OCC2=CC=C3C(C(N(C4C(NC(CC4)=O)=O)C3)=O)=C2
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 (201.87 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

2.0187 mL

10.0933 mL

20.1865 mL

5 mM

0.4037 mL

2.0187 mL

4.0373 mL

10 mM

0.2019 mL

1.0093 mL

2.0187 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)}

In Vivo:

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

Stock Solution Working Solution

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 90% (20% SBE-β-CD in Saline)

Solubility: 2.5 mg/mL (5.05 mM); Suspended solution; Need ultrasonic

This protocol yields a suspended solution of 2.5 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage Dosage
mg/kg
Animal Weight (Per Animal) Animal Weight (Per Animal)
g
Dosing Volume (Per Animal) Dosing Volume (Per Animal)
μL
Number of Animals Number of Animals

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

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

Please enter your animal formula composition:

%
DMSO +

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
%
+
+
%
Tween-80 + +
%
Saline +

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).

Working solution concentration: 0.22 mg/mL

Reinheit & Dokumentation

Select Batch:

Reinheit: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (282 KB)
SDS (418 KB)
- English - EN (418 KB)
- Français - FR (418 KB)
- Deutsch - DE (418 KB)
- Norwegian - NO (418 KB)
- Español - ES (418 KB)
- Swedish - SV (418 KB)
- Italian - IT (418 KB)
- Korean - KR (418 KB)
- Portuguese - PT (418 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]. Gerald Gavory, et al. Identification of MRT-2359, a Potent, Selective and Orally Bioavailable GSPT1-directed Molecular Glue
Degrader (MGD) for the Treatment of Cancers with MYC-induced Translational Addiction.

[2]. Gerald Gavory, et al. Abstract 3449: Development of MRT-2359, an orally bioavailable GSPT1 molecular glue degrader, for the treatment of lung cancers with MYC-induced translational addiction. Cancer Res (2023) 83 (7_Supplement): 3449.

[3]. Gerald Gavory, et al. Abstract 3929: Identification of MRT-2359 a potent, selective and orally bioavailable GSPT1-directed molecular glue degrader (MGD) for the treatment of cancers with Myc-induced translational addiction. Cancer Res (2022) 82 (12_Supplement): 3929.

[4]. Ralph Tiedt, et al. Abstract 3294: The GSPT1 molecular glue degrader MRT-2359 is active against prostate cancer. Cancer Res (2024) 84 (6_Supplement): 3294.

[5]. Chang X, et al. Development and therapeutic potential of GSPT1 molecular glue degraders: A medicinal chemistry perspective. Med Res Rev. 2024 Jul;44(4):1727-1767. [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	2.0187 mL	10.0933 mL	20.1865 mL	50.4663 mL
	5 mM	0.4037 mL	2.0187 mL	4.0373 mL	10.0933 mL
	10 mM	0.2019 mL	1.0093 mL	2.0187 mL	5.0466 mL
	15 mM	0.1346 mL	0.6729 mL	1.3458 mL	3.3644 mL
	20 mM	0.1009 mL	0.5047 mL	1.0093 mL	2.5233 mL
	25 mM	0.0807 mL	0.4037 mL	0.8075 mL	2.0187 mL
	30 mM	0.0673 mL	0.3364 mL	0.6729 mL	1.6822 mL
	40 mM	0.0505 mL	0.2523 mL	0.5047 mL	1.2617 mL
	50 mM	0.0404 mL	0.2019 mL	0.4037 mL	1.0093 mL
	60 mM	0.0336 mL	0.1682 mL	0.3364 mL	0.8411 mL
	80 mM	0.0252 mL	0.1262 mL	0.2523 mL	0.6308 mL
	100 mM	0.0202 mL	0.1009 mL	0.2019 mL	0.5047 mL

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MRT-2359

Apoptosis Compound Library

Anti-Cancer Compound Library

Clinical Compound Library

Drug Repurposing Compound Library

Orally Active Compound Library

Anti-Lung Cancer Compound Library

Anti-Blood Cancer Compound Library

Anti-Prostate Cancer Compound Library

Molecular Glue Compound Library

Highly Selective Activators Library

Cell Death Library

Anti-Hematopathy Compound Library

Bioactive Compound Library Max

MCE Bioactive Compound Library

Drug Repurposing Compound Library Plus

Clinical Compound Library Plus

Bioactive Compound Library

Non-Alcoholic Fatty Liver Disease (NAFLD) Compound Library

High-Throughput Bioactive Compound Library

Molecular Glue-like Compound Library

Biologische Aktivität

Chemical Information

Lösungsmittel & Löslichkeit

Reinheit & Dokumentation

Verweise

Help & FAQs

Complete Stock Solution Preparation Table

MRT-2359

Apoptosis Compound Library

Anti-Cancer Compound Library

Clinical Compound Library

Drug Repurposing Compound Library

Orally Active Compound Library

Anti-Lung Cancer Compound Library

Anti-Blood Cancer Compound Library

Anti-Prostate Cancer Compound Library

Molecular Glue Compound Library

Highly Selective Activators Library

Cell Death Library

Anti-Hematopathy Compound Library

Bioactive Compound Library Max

MCE Bioactive Compound Library

Drug Repurposing Compound Library Plus

Clinical Compound Library Plus

Bioactive Compound Library

Non-Alcoholic Fatty Liver Disease (NAFLD) Compound Library

High-Throughput Bioactive Compound Library

Molecular Glue-like Compound Library

Biologische Aktivität

Chemical Information

Lösungsmittel & Löslichkeit

Reinheit & Dokumentation

Verweise

Help & FAQs

Complete Stock Solution Preparation Table

MRT-2359 Related Classifications

HY-153356 Related Classifications