SD-2301
Based on 1 Customer Validation
SD-2301 is a selective STAT3 PROTAC degrader with a DC50 of 4 nM. By bridging the target protein STAT3 and VHL-1 E3 ubiquitin ligase, SD-2301 induces efficient degradation of STAT3 via the ubiquitin-proteasome system, thereby exerting potent anti-tumor and immunomodulatory effects. SD-2301 can be used in research related to lymphoma, melanoma, colon cancer and other tumors.
(Pink: STAT3 ligand (HY-172947); Blue: VHL ligand (HY-112078); Black: linker (HY-W577012)).
연구목적의 판매만을 진행합니다. 환자를 대상으로 한 판매는 하지 않습니다.
- Purity: 99.89%
- CAS No.: 3054116-24-1
- 화학식: C64H80N13O15PS2
- 분자량:1366.50
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보관:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
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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Biological Activity
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Chemical Information
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용액&용해도
- 순도&문서
- References
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Help & FAQs
Biological Activity
제품 설명
IC50 & Target
[1]|
STAT3 4 nM (IC50) |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| SU-DHL-1 | IC50 |
11 nM
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Cell growth inhibition against human SU-DHL-1 lymphoma cells assessed by CTG assay incubated for 4 days.
Cell growth inhibition against human SU-DHL-1 lymphoma cells assessed by CTG assay incubated for 4 days.
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40369063 |
| SU-DHL-1 | DC50 |
10 nM
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Depletion of STAT3 and phosphorylated STAT3 (pSTAT3Y705) proteins in human SU-DHL-1 cells incubated for 15 h, analyzed by Western blot.
Depletion of STAT3 and phosphorylated STAT3 (pSTAT3Y705) proteins in human SU-DHL-1 cells incubated for 15 h, analyzed by Western blot.
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40369063 |
| PBMC | DC50 |
8 nM
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Depletion of STAT3 protein in human peripheral blood mononuclear cells (PBMCs) incubated for 14 h, analyzed by Western blot.
Depletion of STAT3 protein in human peripheral blood mononuclear cells (PBMCs) incubated for 14 h, analyzed by Western blot.
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40369063 |
In Vitro
SD-2301 (4 days) potently inhibits the proliferation of SU-DHL-1 and SUP-M2 lymphoma cells, with IC50 values of 11 nM and 5 nM, respectively[2].
SD-2301 (3 nM-5 μM; 24 h) potently induces STAT3 degradation in the HiBiT assay system, with a DC50 of 4 nM and a maximum degradation rate > 95%[2].
SD-2301 (0.32-200 nM; 14 h) potently and selectively degrades STAT3, but not other members of the STAT family, in human peripheral blood mononuclear cells (PBMCs), with a DC50 of 8 nM[2].
SD-2301 (0.2-5 μM; 15 h) potently and selectively degrades STAT3 in SU-DHL-1 cells, with no such effect on other members of the STAT family, and its DC50 is 10 nM; meanwhile, this compound upregulates STAT4 levels, and exerts minimal effects on other STAT proteins even at high concentrations[2].
SD-2301 (1 μM; 8 h) is a selective STAT3 degrader in PBMCs, and only reduces the expression levels of 4 off-target proteins by more than 50% at a high concentration of 1 μM[2].
SD-2301 (50 nM; 6 h) fails to degrade STAT3 in SU-DHL-1 cells pretreated with SI-109 (HY-129603), VHL-1 ligand (HY-112078), MLN-4924 (HY-70062) or PR-171 (HY-10455), demonstrating that its degradation mechanism depends on target binding, neddylation and the proteasome pathway[2].
SD-2301 (50 nM; 24 h) potently degrades STAT3 in mouse dendritic cells, and its efficacy is 4 to 5 times higher than that of SD-36[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:Murine bone marrow-derived dendritic cells (BMDCs)
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Concentration:50 nM
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Incubation Time:24 h
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Result:Successfully and potently induced the degradation of STAT3 protein in murine DCs, exhibiting a degradation potency 4 to 5 times higher than that of SD-36.
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Cell Line:SU-DHL-1 cells
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Concentration:50 nM (after pre-treatment with 40 μM SI-109, 20 μM VHL ligand, 0.5 μM MLN-4924, or 0.2 μM PR-171)
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Incubation Time:6 h
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Result:The STAT3 degradation induced by SD-2301 was blocked by high-affinity STAT3 ligand, VHL-1 ligand, neddylation inhibitor (MLN-4924), and proteasome inhibitor (PR-171), proving that the degradation relies on target engagement and the proteasome system.
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Cell Line:Human peripheral blood mononuclear cells (PBMCs), SU-DHL-1 cells
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Concentration:0.32, 1.6, 8, 40, 200 nM (PBMCs); 0.5, 2.4, 12, 60, 200, 300, 1000, 5000 nM
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Incubation Time:14 h (PBMCs), 15 h (SU-DHL-1)
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Result:Potently degraded STAT3 and pSTAT3 (Y705) while exhibiting extremely high selectivity over other STAT family members (STAT1, STAT2, STAT5, STAT6), affecting STAT1 only slightly at high concentrations, and dose-dependently increasing STAT4.
Parmacokinetics
| Species | Dose | Route | CL | Vss | T1/2 | Cmax | AUC0-24 |
|---|---|---|---|---|---|---|---|
| Mice[2] | 5 mg/kg | i.v. | 28.2 mL/h/kg | 140 mL/kg | 3.5 h | 46600 ng/mL | 175724 ng·h/mL |
In Vivo
SD-2301 (10-30 mg/kg; i.v.; once weekly for 4 weeks; observation up to 70 days) induces rapid, complete and durable tumor regression without obvious toxicity in SU-DHL-1 xenograft mouse models[2].
SD-2301 (10 mg/kg once weekly for 2 weeks or 30 mg/kg as a single dose; i.v.; up to 44 days) exerts complete and long-lasting tumor regression with a single administration in the SUP-M2 xenograft mouse model[2].
SD-2301 (5 mg/kg; i.p. or i.v.; once every 3 days) potently inhibits tumor growth in the MC38 syngeneic mouse model of colon cancer, exerts profound synergistic inhibition in combination with anti-PD-L1, and increases the proportion of neoantigen-specific CD8+ T cells within tumors[1].
SD-2301 (5 mg/kg; i.v.; once every 3 days) loses its anti-tumor efficacy in B16F10 tumor-bearing Stat3-/- mice, but remains effective in Stat3+/+ mice, demonstrating that its anti-tumor effect is dependent on the target STAT3[1].
SD-2301 (5 mg/kg; i.v.; once every 3 days) loses its antitumor efficacy in cDC1-deficient Batf3-/- tumor-bearing (MC38) mice, demonstrating that its efficacy depends on cDC1 cells[1].
SD-2301 (5 mg/kg; i.v.; once every 3 days) potently inhibits tumor growth, induces STAT3 degradation in in vivo DCs, promotes effector functions of intratumoral CD8+ T cells, and enhances the maturation and function of cDC1 cells in the B16F10 syngeneic mouse melanoma model, without causing body weight loss in mice or altering tumor vascular density[1].
SD-2301 (5 mg/kg; i.v.; once every 3 days) exerts a synergistic tumor growth inhibitory effect in combination with anti-PD-L1 (HY-108730A) in the B16F10 syngeneic mouse melanoma model[1].
SD-2301 (20 mg/kg; i.v.; single administration; 6-72 h) significantly reduces the STAT3 protein level in spleen tissues of normal C57BL/6 mice without affecting other STAT proteins[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:CB.17 SCID mice (female; lymphoma xenograft model)[2]
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Dosage:30 mg/kg
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Administration:i.v.; single dose; 6, 24, 48 h
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Result:Depleted STAT3 protein by >90% in tumor tissue at 6, 24, and 48 hours post-administration.
Reached tumor tissue concentrations of 14426 ng/mL at 6 hours, 2133 ng/mL at 24 hours, and 490 ng/g at 48 hours; concentrations at 24 and 48 hours were higher than plasma levels.
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Animal Model:CB.17 SCID mice (female)[2]
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Dosage:20 mg/kg
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Administration:i.v.; single dose; 6, 24, 48, 72 h
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Result:Reduced STAT3 protein levels in spleen tissue by 86% at 6 hours, 82% at 24 hours, 68% at 48 hours, and 57% at 72 hours post-administration.
Caused no significant reductions in other STAT protein levels at any time point.
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Animal Model:CB.17 SCID mice (SU-DHL-1 and SUP-M2 xenograft model)[2]
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Dosage:10 mg/kg or 30 mg/kg
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Administration:i.v., once weekly for 4 weeks (SU-DHL-1); once weekly for 2 weeks or single dose (SUP-M2); up to 70 days
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Result:Achieved complete tumor regression in the SU-DHL-1 model (10 and 30 mg/kg) after the second dose.
Attained complete and long-lasting (>30 days) tumor regression with just a single IV dose of 30 mg/kg in the SUP-M2 model.
Was well-tolerated in all treatment groups, with mice showing no significant body weight loss or other signs of toxicity.
Chemical Information
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CAS No. 3054116-24-1
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Appearance Solid
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분자량 1366.50
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화학식 C64H80N13O15PS2
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Color White to off-white
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SMILES
O=C([C@@H](NC([C@@H]1CC[C@@H]2CCN(C[C@@H](C(N12)=O)NC(C3=CC4=C(N3)C=CC(C(P(O)(O)=O)=O)=C4)=O)C(CCCCC5=CN(N=N5)[C@@H](C(C)(C)C)C(N6C[C@@H](C[C@H]6C(N[C@H](C7=CC=C(C=C7)C8=C(N=CS8)C)C)=O)O)=O)=O)=O)CCC(N)=O)NCC(C=C9)=CC=C9S(=O)(CC)=O
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선적
Room temperature in continental US; may vary elsewhere.
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보관
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
용액&용해도
In Vitro:
DMSO : 100 mg/mL (73.18 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. 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. 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: ≥ 2.5 mg/mL (1.83 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.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (1.83 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 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
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.
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.
순도&문서
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Data Sheet (304 KB)
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SDS (254 KB)
- English - EN (254 KB)
- Français - FR (254 KB)
- Deutsch - DE (254 KB)
- Norwegian - NO (254 KB)
- Español - ES (254 KB)
- Swedish - SV (254 KB)
- Italian - IT (254 KB)
- Korean - KR (254 KB)
- Portuguese - PT (254 KB)
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Handling Instructions (2659 KB)
References
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.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 0.7318 mL | 3.6590 mL | 7.3180 mL | 18.2949 mL |
| 5 mM | 0.1464 mL | 0.7318 mL | 1.4636 mL | 3.6590 mL | |
| 10 mM | 0.0732 mL | 0.3659 mL | 0.7318 mL | 1.8295 mL | |
| 15 mM | 0.0488 mL | 0.2439 mL | 0.4879 mL | 1.2197 mL | |
| 20 mM | 0.0366 mL | 0.1829 mL | 0.3659 mL | 0.9147 mL | |
| 25 mM | 0.0293 mL | 0.1464 mL | 0.2927 mL | 0.7318 mL | |
| 30 mM | 0.0244 mL | 0.1220 mL | 0.2439 mL | 0.6098 mL | |
| 40 mM | 0.0183 mL | 0.0915 mL | 0.1829 mL | 0.4574 mL | |
| 50 mM | 0.0146 mL | 0.0732 mL | 0.1464 mL | 0.3659 mL | |
| 60 mM | 0.0122 mL | 0.0610 mL | 0.1220 mL | 0.3049 mL |
SD-2301 Related Classifications
HY-172946 Related Classifications
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