SCR-7952
Based on 1 Customer Validation
SCR-7952 is an orally active MAT2A allosteric inhibitor (IC50 = 18.7 nM; Ki = 14.49 nM; Kd = 0.56 nM). SCR-7952 reduces SAM production, PRMT5 activity, and SDMA marks by binding to the MAT2A allosteric pocket, and dysregulates RNA splicing through FANCA intron retention, thereby selectively inhibiting the proliferation of MTAP-deleted cancer cells and producing synergistic effects with PRMT5 inhibitors. SCR-7952 can be used for research on MTAP-deleted cancers.
Nos produits utilisent uniquement pour la recherche. Nous ne vendons pas aux patients.
- Pureté : 99.34%
- CAS No.: 2798856-04-7
- Formule: C19H15ClN4O
- Masse moléculaire:350.80
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Stockage:
4°C, protect from light
* In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Activité biologique
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Chemical Information
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Solvant et solubilité
- Protocole
- Pureté et documentation
- Références
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Help & FAQs
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Activité biologique
Description
IC50 & Target
[1]|
MAT2A 18.7 nM (IC50) |
MAT2A 14.49 nM (Ki) |
MAT2A 0.56 nM (Kd) |
PRMT5 |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| HCT116 MTAP-de | IC50 |
1.9 nM
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Inhibition of cellular SAM levels in human HCT116 MTAP-/- cells after 6 hrs incubation measured by UPLC-MS/MS.
Inhibition of cellular SAM levels in human HCT116 MTAP-/- cells after 6 hrs incubation measured by UPLC-MS/MS.
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39309689 |
| HCT116 MTAP-de | IC50 |
34.4 nM
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Antiproliferative activity against human HCT116 MTAP-/- cells assessed as viability reduction incubated 6 days by CellTiter-Glo assay.
Antiproliferative activity against human HCT116 MTAP-/- cells assessed as viability reduction incubated 6 days by CellTiter-Glo assay.
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39309689 |
| HCT-116 | IC50 |
487.7 nM
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Antiproliferative activity against human HCT116 WT cells assessed as viability reduction incubated 6 days by CellTiter-Glo assay.
Antiproliferative activity against human HCT116 WT cells assessed as viability reduction incubated 6 days by CellTiter-Glo assay.
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39309689 |
| NCI-H838 | IC50 |
4.3 nM
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Antiproliferative activity against human H838 cells assessed as viability reduction incubated 6 days by CellTiter-Glo assay.
Antiproliferative activity against human H838 cells assessed as viability reduction incubated 6 days by CellTiter-Glo assay.
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39309689 |
| MIA PaCa-2 | IC50 |
19.7 nM
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Antiproliferative activity against human MIA PaCa-2 cells assessed as viability reduction incubated 6 days by CellTiter-Glo assay.
Antiproliferative activity against human MIA PaCa-2 cells assessed as viability reduction incubated 6 days by CellTiter-Glo assay.
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39309689 |
| A549 | IC50 |
123.1 nM
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Antiproliferative activity against human A549 cells assessed as viability reduction incubated 6 days by CellTiter-Glo assay.
Antiproliferative activity against human A549 cells assessed as viability reduction incubated 6 days by CellTiter-Glo assay.
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39309689 |
| WI-38 | IC50 |
988.5 nM
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Antiproliferative activity against human WI-38 cells assessed as viability reduction incubated 6 days by CellTiter-Glo assay.
Antiproliferative activity against human WI-38 cells assessed as viability reduction incubated 6 days by CellTiter-Glo assay.
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39309689 |
| HCT116 MTAP-de | IC50 |
2 nM
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Inhibition of cellular SAM production in HCT116 MTAP-/- cells.
Inhibition of cellular SAM production in HCT116 MTAP-/- cells.
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1538-7445.AM2022-5434 |
| HCT116 MTAP-de | IC50 |
53 nM
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Inhibition of HCT116 MTAP-/- cell growth in proliferation assay.
Inhibition of HCT116 MTAP-/- cell growth in proliferation assay.
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1538-7445.AM2022-5434 |
In Vitro
SCR-7952 (12.5-200 nM) binds MAT2A with a KD of 0.56 nM in SPR[1].
SCR-7952 (10 µM highest concentration; 6 h) decreases cellular SAM in HCT116 MTAP-/- cells with an IC50 of 1.9 nM[1].
SCR-7952 (10-1000 nM; 96 h) dose-dependently upregulates MAT2A and decreases SDMA in HCT116 MTAP-/- cells[1].
SCR-7952 exhibits synergy with SAM-competitive or MTA-cooperative PRMT5 inhibitors in HCT116 MTAP-/- and KP4 cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:HCT116 and HCT116 MTAP-/- cells
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Concentration:10, 30, 100, 300, 1000 nM
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Incubation Time:96 h
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Result:Dose-dependently upregulates MAT2A and decreases SDMA in HCT116 MTAP-/- cells.
Parmacokinetics
| Species | Dose | Route | AUC0-24 |
|---|---|---|---|
| Mice[1] | 1.0 mg/kg | p.o. | 1442 ng/mL·h |
In Vivo
SCR-7952 (0.3 mg/kg; p.o.; once daily) combined with Onametostat (JNJ-64619178) (HY-101564) produces near-complete tumor stasis in the HCT116 MTAP-/- xenograft model, with a TGI of 94.4%[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Nu/Nu (female)[1]
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Dosage:0.25, 0.5, 1.0, or 3.0 mg/kg
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Administration:p.o. (oral gavage); once daily (q.d.)
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Result:Compared with the vehicle group, oral administration of SCR-7952 led to a significant dose-dependent reduction in tumor growth.
Tumor growth inhibition (TGI) was 60.0% at 0.5 mg/kg, 62.7% at 1.0 mg/kg, and 82.9% at 3.0 mg/kg.
In a satellite group, SAM levels in HCT116 MTAP-/- xenograft tumors and mouse plasma were significantly decreased, with 53.56-68.72% inhibition at 2 or 4 h post final dose in the low group.
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Animal Model:Nu/Nu (female)[1]
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Dosage:0.3 mg/kg
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Administration:p.o. (oral gavage); once daily (q.d.)
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Result:Modest efficacy was observed with either SCR-7952 (0.3 mg/kg) or JNJ-64619178 (1.0 mg/kg) alone.
Almost complete tumor stasis was achieved when both agents were combined, significantly better than monotherapies (TGI 94.4% vs. 55.0% vs. 54.0%).
SCR-7952 (0.3 mg/kg) or JNJ-64619178 (1.0 mg/kg) alone both led to a remarkable reduction of SDMA levels.
In the combination group, a significant reduction of SDMA levels was observed compared with single-agent groups.
Chemical Information
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CAS No. 2798856-04-7
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Appearance Solid
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Masse moléculaire 350.80
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Formule C19H15ClN4O
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Color White to off-white
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SMILES
O=C1N(C2=CC=CN=C2C3CC3)C4=C(C=CC(Cl)=C4)C5=C1N=CN5C
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
4°C, protect from light
* In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)
Solvant et solubilité
In Vitro:
DMSO : 2 mg/mL (5.70 mM; ultrasonic and warming and heat to 60°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
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 (protect from light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
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 (protect from light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
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.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: 0.5 mg/mL (1.43 mM); Clear solution; Need ultrasonic
This protocol yields a clear solution of 0.5 mg/mL.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (5.0 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:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%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
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL. * In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
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.
Pureté et documentation
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Fiche technique (286 KB)
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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)
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Instruction de manipulation (2659 KB)
Références
[1]. Yu Z, et al. SCR-7952, a highly selective MAT2A inhibitor, demonstrates synergistic antitumor activities in combination with the -adenosylmethionine-competitive or the methylthioadenosine-cooperative protein arginine methyltransferase 5 inhibitors in methylthioadenosine phosphorylase-deleted tumors. MedComm. 2024 Oct;5(10):e705. [Content Brief]
[2]. Yang S, et al. Discovery of Novel Spirocyclic MAT2A Inhibitors Demonstrating High In Vivo Efficacy in MTAP-Null Xenograft Models. Journal of medicinal chemistry. 2025 Feb 13;68(3):3480-3494. [Content Brief]
[6]. Zhou Y, et al. Structure-Based Discovery of a Series of Novel MAT2a Inhibitors. ACS medicinal chemistry letters. 2025 Apr 10;16(4):646-650. [Content Brief]
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 (protect from light). 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 | 2.8506 mL | 14.2531 mL | 28.5063 mL | 71.2657 mL |
| 5 mM | 0.5701 mL | 2.8506 mL | 5.7013 mL | 14.2531 mL |
SCR-7952 Related Classifications
HY-169257 Related Classifications
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