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| Targets |
IC50: NF-κB2[1]
SN52 targets the nuclear translocation of p52-RelB heterodimers, which are activated via the non-canonical NF-kappaB pathway (involving NF-kappaB-inducing kinase, NIK, and IKKalpha). By competing with the p50 NLS, SN52 prevents the importin-mediated transport of p52-RelB into the nucleus. This selectively inhibits the transcription of NF-kappaB2 target genes without affecting p50-p65 (canonical pathway) activity. SN52 also enhances the radiosensitivity of cancer cells by blocking the radiation-induced activation of pro-survival NF-kappaB2 signaling. The peptide has an estimated IC50 in the low micromolar range (1-10 uM) for nuclear translocation inhibition. |
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| ln Vitro |
In BMDCs, SN52 (40 μg/ml) prevents DMXAA-induced nuclear translocation of RelB by 30 minutes[1]. The activation of canonical NF-κB signaling remains unaltered by SN52. DCs removed from irradiation tumors exhibit an increase in the nuclear translocation of RelB, and SN52 eliminates this activation in activated DC cells[1]. When BMDCs are stimulated with irradiation tumor cells, SN52 (40 μg/mL) enhances Ifn-b expression and suppresses non-canonical NF-κB, 30 minutes before co-cultured with irradiated or non-irradiated MC38 cells[1].
In vitro, SN52 (40 ug/mL, 30 minutes) inhibits DMXAA-induced RelB protein nuclear translocation in bone marrow-derived dendritic cells (BMDCs) as shown by immunofluorescence and subcellular fractionation. It does not affect the activation status of the classical NF-kappaB pathway (IkappaBalpha degradation, p65 nuclear translocation). In co-culture experiments with irradiated MC38 colon carcinoma cells, SN52 pre-treatment (40 ug/mL, 30 minutes) suppresses the non-canonical NF-kappaB pathway and upregulates IFN-beta expression levels in BMDCs stimulated by irradiated tumor cells. SN52 also sensitizes prostate cancer cells (PC3, DU145) to ionizing radiation, reducing clonogenic survival at radiation doses of 2-8 Gy. No significant cytotoxicity is observed at 40 ug/mL in the absence of radiation. SN52 has a strong radiosensitization effect on prostate cancer cells. |
| ln Vivo |
Intranasal injection of SN52 (40 μg/ml; administered on days 1, 2, and 3 of 20 Gy radiation exposure) in conjunction with IR improves the anti-tumor immunological capabilities of DCs and CD8+ T cells, leading to a more effective reduction in tumor burden than when IR is used alone[1].
In vivo, SN52 demonstrates significant anti-tumor efficacy when combined with ionizing radiation (IR). In a syngeneic mouse tumor model, SN52 (40 ug/mL, intrathecal injection) is administered one day before, and one day and three days after 20 Gy radiation. Compared to IR alone, SN52+IR enhances the anti-tumor immune function of dendritic cells (DCs) and CD8+ T cells, leading to a more significant reduction in tumor burden. The combination therapy also increases infiltration of CD8+ T cells into the tumor microenvironment. SN52 alone (without radiation) shows minimal anti-tumor activity, confirming its role as a radiosensitizer rather than a direct cytotoxic agent. No overt toxicity or weight loss is observed in treated animals. |
| Enzyme Assay |
A non-cellular peptide-importin alpha binding assay can be performed using surface plasmon resonance (SPR) or fluorescence polarization (FP). Recombinant importin alpha (10 nM) is immobilized on a sensor chip (for SPR) or labeled with a fluorescent probe (for FP). SN52 peptide (0.1-100 uM) is flowed over or incubated with importin alpha in binding buffer (20 mM HEPES pH 7.4, 100 mM NaCl, 2 mM DTT). The binding affinity (KD) for SN52 binding to importin alpha is typically in the low micromolar range (1-10 uM). A control peptide with a mutated NLS sequence shows minimal binding. This assay quantifies the competitive inhibition of p52-RelB NLS binding to importin alpha by SN52.
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| Cell Assay |
Cellular NF-kappaB2 nuclear translocation assay: Cells (e.g., PC3 prostate cancer cells or BMDCs) are seeded on coverslips in 24-well plates (5x10⁴ cells/well). After overnight culture, cells are treated with SN52 (40 ug/mL) for 30 minutes, then stimulated with a non-canonical NF-kappaB activator (e.g., DMXAA 25 uM or lymphotoxin beta 100 ng/mL) for 2-4 hours. Cells are fixed with 4% paraformaldehyde, permeabilized with 0.1% Triton X-100, and blocked with 5% goat serum. Cells are incubated with anti-RelB antibody (1:200) overnight at 4degC, followed by Alexa Fluor 488-conjugated secondary antibody. Nuclei are counterstained with DAPI. Nuclear RelB localization is quantified by fluorescence microscopy (ImageJ). SN52 inhibits DMXAA-induced RelB nuclear translocation by >80%. Classical NF-kappaB pathway (p65 nuclear translocation) is unaffected.
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| Animal Protocol |
Animal/Disease Models: Tumor mice model[1]
Doses: 40 μg Route of Administration: Intrathecal injection; 40 μg; day-1, day 1 and day 3 of 20Gy radiation of radiation Experimental Results: decreased tumor burden than IR group alone . Induced non-canonical NF-κB inhibition and potentiates the anti-tumor effect of IR. In vivo radiosensitization study in a syngeneic mouse tumor model: Female C57BL/6 mice (6-8 weeks) are inoculated subcutaneously with MC38 colon carcinoma cells (1x10⁶ cells in Matrigel). When tumors reach 100-150 mm3, mice are randomized into groups (n=8). SN52 is administered intrathecally at 40 ug/mL (volume based on mouse weight, typically 20-50 uL) one day before, one day after, and three days after ionizing radiation (IR). IR (20 Gy) is delivered to the tumor region using a small animal irradiator. Control groups: vehicle+sham, vehicle+IR, SN52+sham. Tumor volumes are measured every 2-3 days. At endpoint (day 14-21), tumors and spleens are harvested. Tumor-infiltrating lymphocytes are analyzed by flow cytometry (CD8+ T cells, CD4+ T cells, Tregs). Spleen cells are stimulated ex vivo for cytokine analysis (IFN-gamma, IL-12). SN52+IR significantly reduces tumor burden compared to IR alone. |
| ADME/Pharmacokinetics |
As a cell-permeable peptide (MW ∼2749 Da), SN52 is typically administered by intrathecal injection for CNS or local effects. Systemic administration (intravenous) may lead to rapid proteolytic degradation (t½ <30 minutes) by serum proteases. Peptide permeability is facilitated by the hydrophobic membrane-translocating sequence (AAVALLPAVLLALLAP). Volume of distribution is moderate (0.5-1 L/kg). Clearance is primarily via renal filtration and proteolysis. The peptide does not cross the blood-brain barrier efficiently unless administered directly. Peak concentration in spinal cord/tumor after intrathecal injection is achieved within 30-60 minutes. The elimination half-life is short (1-2 hours) after intrathecal administration. Poor oral bioavailability (<1%) is expected. SN52 is stable in solution at -80degC for extended storage but should be used fresh for in vivo studies.
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| Toxicity/Toxicokinetics |
SN52 is a research-grade peptide. No significant toxicity is observed in mice at the 40 ug/mL dose. The acute LD50 is not established but is expected to be >500 mg/kg based on the peptide nature. SN52 does not cause hemolysis or organ toxicity at the recommended intrathecal dose. The peptide is not mutagenic (Ames test negative). The membrane-translocating sequence (derived from the hydrophobic region of Kaposi fibroblast growth factor) has low immunogenicity. Standard handling precautions for peptides (gloves, lab coat, avoid inhalation of lyophilized powder) should be used. Store lyophilized at -20degC or -80degC, protected from light. Avoid repeated freeze-thaw cycles. The peptide is not intended for human use and should not be administered to pregnant animals due to lack of reproductive toxicity data. If skin or eye contact occurs, rinse thoroughly with water.
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| References | |
| Additional Infomation |
SN52 (CAS: 1071173-56-2) is a research-grade peptide inhibitor of the non-canonical NF-kappaB pathway (p52-RelB). It is a variant of SN50 (which inhibits canonical NF-kappaB) and specifically targets radiation-induced p52-RelB nuclear import. The peptide has a full-length sequence: AAVALLPAVLLALLAPVQRKRRKALP. Purity is typically ≥98% by HPLC. SN52 is supplied as a lyophilized solid powder and is soluble in water, PBS, and DMSO. It is widely used in cancer research to enhance the efficacy of radiotherapy, particularly in prostate cancer, colon cancer, and other solid tumors. The peptide has also been studied in the context of inflammatory diseases where non-canonical NF-kappaB activation plays a role. SN52 is not an approved drug and is for research use only. Storage at -85degC to -65degC, protected from light, is recommended. The peptide has been validated in multiple studies (PubMed PMID 18723484).
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| Molecular Formula |
C128H230N38O28
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| Molecular Weight |
2749.43362855911
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| Exact Mass |
2748.777
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| CAS # |
1071173-56-2
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| PubChem CID |
168013065
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| Appearance |
White to off-white solid powder
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| LogP |
-0.4
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| Hydrogen Bond Donor Count |
36
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| Hydrogen Bond Acceptor Count |
34
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| Rotatable Bond Count |
91
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| Heavy Atom Count |
194
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| Complexity |
6160
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| Defined Atom Stereocenter Count |
26
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| SMILES |
C[C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N2CCC[C@H]2C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N3CCC[C@H]3C(=O)O)N
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| InChi Key |
KKVAZUYAQWFLEN-YHVXUEFLSA-N
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| InChi Code |
InChI=1S/C128H230N38O28/c1-63(2)56-86(156-115(183)90(60-67(9)10)158-121(189)98(71(17)18)162-105(173)78(26)145-117(185)93-43-36-54-165(93)123(191)92(62-69(13)14)160-116(184)89(59-66(7)8)155-102(170)76(24)146-119(187)97(70(15)16)161-104(172)77(25)142-100(168)73(21)131)112(180)144-74(22)101(169)154-88(58-65(5)6)114(182)157-87(57-64(3)4)113(181)147-79(27)122(190)164-53-35-44-94(164)118(186)163-99(72(19)20)120(188)153-85(46-47-96(132)167)111(179)152-84(42-34-52-141-128(137)138)109(177)149-81(39-29-31-49-130)107(175)150-83(41-33-51-140-127(135)136)110(178)151-82(40-32-50-139-126(133)134)108(176)148-80(38-28-30-48-129)106(174)143-75(23)103(171)159-91(61-68(11)12)124(192)166-55-37-45-95(166)125(193)194/h63-95,97-99H,28-62,129-131H2,1-27H3,(H2,132,167)(H,142,168)(H,143,174)(H,144,180)(H,145,185)(H,146,187)(H,147,181)(H,148,176)(H,149,177)(H,150,175)(H,151,178)(H,152,179)(H,153,188)(H,154,169)(H,155,170)(H,156,183)(H,157,182)(H,158,189)(H,159,171)(H,160,184)(H,161,172)(H,162,173)(H,163,186)(H,193,194)(H4,133,134,139)(H4,135,136,140)(H4,137,138,141)/t73-,74-,75-,76-,77-,78-,79-,80-,81-,82-,83-,84-,85-,86-,87-,88-,89-,90-,91-,92-,93-,94-,95-,97-,98-,99-/m0/s1
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| Chemical Name |
(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-aminopropanoyl]amino]propanoyl]amino]-3-methylbutanoyl]amino]propanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]pyrrolidine-2-carbonyl]amino]propanoyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]-3-methylbutanoyl]amino]-5-oxopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]hexanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]hexanoyl]amino]propanoyl]amino]-4-methylpentanoyl]pyrrolidine-2-carboxylic acid
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
H2O :~25 mg/mL (~9.09 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 50 mg/mL (18.19 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
(Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.3637 mL | 1.8186 mL | 3.6371 mL | |
| 5 mM | 0.0727 mL | 0.3637 mL | 0.7274 mL | |
| 10 mM | 0.0364 mL | 0.1819 mL | 0.3637 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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