MD-265
Based on 1 Customer Validation
MD-265 is a PROTAC degrader targeting MDM2, which activates p53 in cancer cells carrying wild-type p53. MD-265 induces MDM2 degradation by recruiting the CRL4-CRBN ligase complex via the ubiquitination and proteasomal degradation pathway. MD-265 upregulates p53 target genes, induces apoptosis, reduces Mcl-1 levels, increases caspase-3 cleavage, and inhibits colony formation of wild-type p53 leukemia stem cells. MD-265 can be used in research related to leukemia and acute myeloid leukemia.
(Pink: MDM-2/p53 ligand (HY-133754); Blue: Cereblon ligand (HY-A0003); Black: linker).
商品は「研究用試薬」です。人や動物の医療用・臨床診断用・食品用の製品ではありません。
研究用途以外に使用した場合、当社は一切の責任を負いかねます。
- 純度: 99.31%
- CAS 番号: 2415160-21-1
- 分子式: C50H51Cl2FN6O6
- 分子量:921.88
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保管条件:
-20°C, protect from light, stored under nitrogen
* In solvent : -80°C, 6 months; -20°C, 1 month (protect from light, stored under nitrogen)
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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生物活性
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化学情報
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溶剤 & 溶解度
- 純度とドキュメンテーション
- 参考文献
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Help & FAQs
生物活性
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MDM2 |
Mcl-1 |
Caspase 3 |
p53 |
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| RS4-11 | IC50 |
0.9 nM
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Inhibits RS4-11 cells growth.
Inhibits RS4-11 cells growth.
|
39480241 |
| MV4-11 | IC50 |
2.9 nM
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Inhibits MV4-11 cells growth.
Inhibits MV4-11 cells growth.
|
39480241 |
| OCI-AML2 | IC50 |
24 nM
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Inhibits OCI-AML2 cells growth.
Inhibits OCI-AML2 cells growth.
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39480241 |
| OCI-AML-3 | IC50 |
212 nM
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Inhibits OCI-AML-3 cells growth.
Inhibits OCI-AML-3 cells growth.
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39480241 |
| OCI-AML-5 | IC50 |
23 nM
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Inhibits OCI-AML-5 cells growth.
Inhibits OCI-AML-5 cells growth.
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39480241 |
| MOLM-13 | IC50 |
5.7 nM
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Inhibits MOLM-13 cells growth.
Inhibits MOLM-13 cells growth.
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39480241 |
| MOLM-14 | IC50 |
7.6 nM
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Inhibits MOLM-14 cells growth.
Inhibits MOLM-14 cells growth.
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39480241 |
| ML-2 | IC50 |
1.2 nM
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Inhibits ML-2 cells growth.
Inhibits ML-2 cells growth.
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39480241 |
| SIG-M5 | IC50 |
20 nM
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Inhibits SIG-M5 cells growth.
Inhibits SIG-M5 cells growth.
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39480241 |
MD-265 (1 nM-1 μM; 4 days) potently inhibits the proliferation of RS4;11 leukemia cells carrying wild-type p53, with an IC50 of 0.7 nM, and shows no activity in p53-mutant RS4;11Mut cells[1].
MD-265 (1 nM-10 μM; 4 days) potently inhibits the proliferation of MV4;11 leukemia cells carrying wild-type p53, with an IC50 of 2 nM[1].
MD-265 (serial dilution; 4 days) potently inhibits the growth of multiple wild-type p53 acute leukemia cell lines, with an IC50 value ranging from 0.9 nM to 212 nM[1].
MD-265 (1-10 nM; 2 h) depletes MDM2 protein and activates p53 in RS4;11 wild-type p53 leukemia cells, and this effect is exerted at concentrations as low as 1 nM after 2 h of treatment[1].
MD-265 (3-30 nM; 2 h) activates p53, and treatment at concentrations as low as 3 nM for 2 h does not upregulate MDM2 protein in MV4;11 wild-type p53 leukemia cells[1].
MD-265 (10 nM; 3 h) treatment of RS4;11 wild-type p53 leukemia cells significantly elevates the mRNA expression of p53 target genes MDM2, p21 and PUMA by 8–10 fold after 3 h incubation, while showing no impact on TP53 mRNA levels[1].
MD-265 (30 nM; 3 h) upregulates the mRNA levels of p53 target genes MDM2, p21 and PUMA in MV4;11 wild-type p53 leukemia cells after 3 hours of treatment, but has no effect on TP53 mRNA[1].
MD-265 (3 nM; 2 h) induces MDM2 degradation and p53 activation in RS4;11 wild-type p53 leukemia cells, and this effect can be abrogated by co-treatment with 20 μM Lenalidomide (HY-A0003)[1].
MD-265 (serial dilutions; 4 days) exhibits cell growth inhibitory activity in wild-type p53 RS4;11 leukemia cells following 4 days of incubation, and this activity can be attenuated by combination treatment with 20 μM Lenalidomide[1].
MD-265 (serial dilutions; 4 days) exerts growth inhibitory effects on wild-type p53 MV4;11 leukemia, and combination with 20 μM Lenalidomide attenuates this activity[1].
MD-265 (serial dilution; 4 days) requires effective simultaneous binding to both MDM2 and cereblon to exert potent cell growth inhibitory effects on RS4;11 wild-type p53 leukemia cells[1].
MD-265 (10-100 nM; 2 weeks) inhibits colony formation in sensitive primary human AML LSCs, but exerts no effect on drug-resistant primary human AML LSCs[2].
MD-265 (72 h) potently induces cytotoxicity in primary human AML LSCs, with a median IC50 of 16 nM, and sensitivity is restricted to LSCs with functional TP53 and detectable MDM2/MDM4 expression[2].
Studies on MD-265 (72 h) show that normal human CD34+ hematopoietic stem and progenitor cells (HSPCs) are 100-fold less sensitive to it than primary human acute myeloid leukemia stem cells (AML LSCs), with a median IC50 of 818 nM[2].
MD-265 (10-1000 nM; 4 h) depletes MDM2 protein, induces p53, and activates apoptotic pathways in sensitive primary human AML LSCs, without triggering feedback upregulation of MDM2[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:RS4;11 wild-type p53 precursor cell lymphoblastic leukemia cells
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Concentration:1 nM; 10 nM; 100 nM; 1 μM
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Incubation Time:4 days
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Result:Potently inhibited RS4;11 cell growth with an IC50 of 0.7 nM, which was more potent than MD-224 (IC50 = 2 nM), degrader 8 (IC50 = 1 nM), degrader 26 (IC50 = 3 nM), and the MDM2 inhibitor MI-1063 (IC50 = 179 nM).
Showed no cell growth inhibition activity (IC50 > 1000 nM) in RS4;11Mut cells harboring p53 hot-spot mutations Y236H and R249G.
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Cell Line:MV4;11 wild-type p53 acute biphenotypic B myelomonocytic leukemia cells
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Concentration:1 nM; 10 nM; 100 nM; 1 μM; 10 μM
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Incubation Time:4 days
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Result:Inhibited MV4;11 cell growth with an IC50 of 2 nM, which was more potent than MD-224 (IC50 = 7 nM) and MI-1063 (IC50 = 93 nM).
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Cell Line:panel of wild-type p53 acute leukemia cell lines (OCI-AML-2, OCI-AML-3, OCI-AML-5, MOLM-13, MOLM-14, mL-2, SIG-M5)
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Concentration:serial dilutions
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Incubation Time:4 days
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Result:Potently inhibited cell growth across all tested wild-type p53 acute leukemia cell lines, with IC50 values ranging from 0.9 nM (RS4;11) to 212 nM (OCI-AML-3).
Was >3-times more potent than degrader 26 and >5-197 times more potent than the MDM2 inhibitor MI-1061 in each cell line.
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Cell Line:RS4;11 wild-type p53 leukemia cells
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Concentration:1 nM, 3 nM, 10 nM
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Incubation Time:2 h
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Result:Dramatically increased p53 protein levels at concentrations as low as 1-3 nM after 2 h, while significantly reducing MDM2 protein levels compared to untreated controls.
In contrast, the MDM2 inhibitor MI-1061 increased both p53 and MDM2 protein levels.
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Cell Line:MV4;11 wild-type p53 leukemia cells
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Concentration:3 nM, 10 nM, 30 nM
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Incubation Time:2 h
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Result:Increased p53 protein levels after 2 h, did not increase MDM2 protein levels compared to untreated controls, and did not cause the MDM2 upregulation seen with MI-1061 treatment.
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Cell Line:RS4;11 wild-type p53 leukemia cells
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Concentration:10 nM
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Incubation Time:3 h
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Result:Increased MDM2, p21, and PUMA mRNA levels by 8−10 fold, and had no effect on TP53 mRNA levels.
Was at least as effective as MI-1063 at 300 nM.
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Cell Line:MV4;11 wild-type p53 leukemia cells
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Concentration:30 nM
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Incubation Time:3 h
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Result:Increased MDM2 and p21 mRNA levels by 10-fold, PUMA mRNA levels by 3-fold, and had no effect on TP53 mRNA levels.
Was more effective than MI-1063 at 300 nM.
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Cell Line:RS4;11 wild-type p53 leukemia cells
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Concentration:3 nM MD-265; 20 μM lenalidomide (co-treated)
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Incubation Time:2 h
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Result:Co-treatment with lenalidomide attenuated MD-265-induced MDM2 depletion and reduced p53 protein levels compared to MD-265 alone.
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Cell Line:MV4;11 wild-type p53 leukemia cells
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Concentration:3 nM MD-265; 20 μM lenalidomide (co-treated)
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Incubation Time:2 h
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Result:Co-treatment with lenalidomide attenuated MD-265-induced effects on MDM2 and p53 protein levels compared to MD-265 alone.
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Cell Line:RS4;11 wild-type p53 leukemia cells
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Concentration:serial dilutions of MD-265; 20 μM lenalidomide (co-treated)
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Incubation Time:4 days
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Result:Co-treatment with lenalidomide effectively reduced the cell growth inhibition activity of MD-265.
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Cell Line:MV4;11 wild-type p53 leukemia cells
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Concentration:serial dilutions of MD-265; 20 μM lenalidomide (co-treated)
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Incubation Time:4 days
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Result:Co-treatment with lenalidomide effectively reduced the cell growth inhibition activity of MD-265.
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Cell Line:RS4;11 wild-type p53 leukemia cells
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Concentration:serial dilutions
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Incubation Time:4 days
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Result:Control compounds 30a and 30b showed much weaker cell growth inhibition activity than MD-265.
MD-265 (25-50 mg/kg; i.v.; weekly) increases median survival of mice with disseminated RS4;11 leukemia by at least 24.5 days, or ≥31%[1].
MD-265 (25 mg/kg; i.v.; once a week; 7 weeks) provides a significant survival benefit in AML PDX models, with complete tumor burden reduction, delayed leukemia repopulation post-treatment, and an acceptable tolerability profile[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:SCID mice[1]
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Dosage:25 mg/kg (initial treatment); 25 mg/kg (retreatment)
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Administration:i.v.; every other day; 14 days (initial treatment); i.v.; 3 doses (retreatment)
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Result:Reduced tumor size by >70% after a single dose.
Reduced all tumors to unmeasurable size after 2 doses.
Maintained complete tumor regression for 34 days after the last dose.
Induced tumor regression again in 4 of 5 regrown tumors with retreatment.
Kept 1 mouse tumor-free for 127 days.
Showed no signs of toxicity or weight loss.
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Animal Model:NOD-SCID mice (female, 5−6 weeks old, cyclophosphamide preconditioned)[1]
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Dosage:25 mg/kg; 50 mg/kg
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Administration:i.v.; weekly
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Result:Extended median survival time to 78.5 days with 25 mg/kg treatment (p < 0.0001 vs control).
Extended median survival time to 72 days with 50 mg/kg treatment (p < 0.0001 vs control).
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Animal Model:NSG-SGM3 (6 to 8 weeks old; sublethally irradiated; injected via tail vein with 500,000 to 1 million CD34-positive-enriched AML patient cells)[2]
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Dosage:25 mg/kg
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Administration:i.v.; once a week; 7 weeks
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Result:Reduced xenograft tumor growth, with complete reduction of human CD45+ cell burden below flow cytometry detection limits within 3 weeks of treatment.
Exhibited slower repopulation of human leukemia cells compared to inhibitor-treated mice after treatment cessation.
Prolonged overall survival relative to vehicle and MDM2 inhibitor groups; median survival was undefined, compared to 19 days for vehicle-treated mice.
Caused no weight loss.
化学情報
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CAS 番号 2415160-21-1
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性状 Solid
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分子量 921.88
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分子式 C50H51Cl2FN6O6
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Color White to off-white
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SMILES
O=C([C@H]1CC[C@@H](CC1)NC([C@@H]2NC3(CCCCC3)[C@]4(C5=CC=C(C=C5NC4=O)Cl)[C@H]2C6=CC=CC(Cl)=C6F)=O)N7CCC(C#CC8=C(C(C9=O)=CC=C8)CN9C(C(N%10)=O)CCC%10=O)CC7
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輸送条件
Room temperature in continental US; may vary elsewhere.
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保管条件
-20°C, protect from light, stored under nitrogen
* In solvent : -80°C, 6 months; -20°C, 1 month (protect from light, stored under nitrogen)
溶剤 & 溶解度
DMSO : 100 mg/mL (108.47 mM; Need ultrasonic; 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, stored under nitrogen). 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, stored under nitrogen). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
濃度 (開始) × 体積 (開始) = 濃度 (終了) × 体積 (終了)
純度とドキュメンテーション
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データシート (294 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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取扱説明書 (2659 KB)
参考文献
[1]. Aguilar A, et al. Discovery of MD-265: A Potent MDM2 Degrader That Achieves Complete Tumor Regression and Improves Long-Term Survival of Mice with Leukemia. Journal of medicinal chemistry. 2024 Nov 14;67(21):19503-19518. [Content Brief]
[2]. Kandarpa M, et al. Activity of PROTAC MDM2 degrader in primary leukemia cells and PDX models. Leukemia. 2026 May;40(5):918-924. [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, stored under nitrogen). 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 | 1.0847 mL | 5.4237 mL | 10.8474 mL | 27.1185 mL |
| 5 mM | 0.2169 mL | 1.0847 mL | 2.1695 mL | 5.4237 mL | |
| 10 mM | 0.1085 mL | 0.5424 mL | 1.0847 mL | 2.7118 mL | |
| 15 mM | 0.0723 mL | 0.3616 mL | 0.7232 mL | 1.8079 mL | |
| 20 mM | 0.0542 mL | 0.2712 mL | 0.5424 mL | 1.3559 mL | |
| 25 mM | 0.0434 mL | 0.2169 mL | 0.4339 mL | 1.0847 mL | |
| 30 mM | 0.0362 mL | 0.1808 mL | 0.3616 mL | 0.9039 mL | |
| 40 mM | 0.0271 mL | 0.1356 mL | 0.2712 mL | 0.6780 mL | |
| 50 mM | 0.0217 mL | 0.1085 mL | 0.2169 mL | 0.5424 mL | |
| 60 mM | 0.0181 mL | 0.0904 mL | 0.1808 mL | 0.4520 mL | |
| 80 mM | 0.0136 mL | 0.0678 mL | 0.1356 mL | 0.3390 mL | |
| 100 mM | 0.0108 mL | 0.0542 mL | 0.1085 mL | 0.2712 mL |
MD-265 関連分類
HY-169327 関連分類
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