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| Targets |
SOP-1812 targets and binds to G-quadruplex (G4) arrangements, which are four-stranded DNA secondary structures formed in guanine-rich sequences of the genome. G4s are particularly prevalent in the promoter regions of several cancer-related genes, including the hTERT (telomerase reverse transcriptase) promoter and HuTel21. SOP-1812 exhibits strong affinity for hTERT G4 with a KD of 4.9 nM and for HuTel21 G4 with a KD of 28.4 nM. By binding to these structures, SOP-1812 downregulates multiple cancer gene pathways, including Wnt/beta-catenin, Hippo, MAPK, and Rap1 signaling pathways.
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| ln Vitro |
HuTel21 G4 and hTERT G4 have a quarterly affinity for SOP1812 (0 -800 nM; 6-24 h) [1]. 40 nM; 6–24 hours) impacts the pigments Rap1, Hippo, MAPK, and Wnt/β-catenin [1].
In vitro, SOP-1812 exhibits potent anti-proliferative activity against human pancreatic cancer cell lines. In MIA PaCa-2, PANC-1, Capan-1, and BxPC-3 cells, SOP-1812 demonstrates GI50 values of 1.3, 1.4, 5.9, and 2.6 nM, respectively, after 96 hours of treatment. It binds to hTERT G4 and HuTel21 G4 with KD values of 4.9 and 28.4 nM, respectively. At a concentration of 40 nM, SOP-1812 affects the expression of WNT5B, DVL1, AXIN, and APC2, and modulates the Wnt/beta-catenin pathway, as well as Axon guidance, Hippo, MAPK, and Rap1 pathways. In vitro studies demonstrate its anti-tumor activity through G4 binding and gene pathway modulation. |
| ln Vivo |
MIA PaCa-2 xenograft mice and KPC transplanted mice demonstrated anti-tumor activity in response to intravenous administration of SOP1812 (1 mg/kg) once or twice weekly for 28 days [1].
In vivo, SOP-1812 demonstrates significant anti-tumor activity in mouse xenograft models. In MIA PaCa-2 xenograft mice (subcutaneous tumors), intravenous administration of SOP-1812 at a dose of 1 mg/kg once or twice weekly for 28 days results in several animals achieving complete tumor regression with no obvious tumor regrowth by day 28. In KPC mice (a transgenic mouse model of pancreatic ductal adenocarcinoma with PDAC symptoms), intravenous injection of SOP-1812 at 1 mg/kg once weekly for 3 consecutive weeks dramatically prolongs survival, with better efficacy than gemcitabine, a standard chemotherapy agent for pancreatic cancer. |
| Enzyme Assay |
For non-cell-based G4 binding assays, a standard protocol uses a fluorescence polarization (FP) or FRET-based DNA melting assay. For FP, a fluorescently labeled G4-forming DNA oligonucleotide (e.g., labeled with 6-FAM at the 5' end) is folded into a G4 structure by heating in 50 mM Tris-HCl buffer (pH 7.5) containing 100 mM KCl and then cooling slowly to room temperature. Varying concentrations of SOP-1812 (0.1-1000 nM) are mixed with the labeled G4 DNA (10 nM) in binding buffer (20 mM Tris-HCl, pH 7.5, 100 mM KCl, 0.1 mg/mL BSA). After incubation at 25degC for 30-60 minutes, the fluorescence polarization (excitation 485 nm, emission 530 nm) is measured. The KD value is calculated from the saturation binding curve. For FRET-based melting assays, a doubly labeled G4 DNA (3'-FAM, 5'-TAMRA) is used; SOP-1812 stabilizes the G4 structure, increasing the melting temperature (Tm).
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| Cell Assay |
Cell Proliferation Assay[1]
Cell Types: MIA PaCa-2, PANC-1, Capan- 1 and BxPC-3 Cell Line Tested Concentrations: 0-50 nM Incubation Duration: 96 hrs (hours) Experimental Results: For MIA PaCa-2, PANC-1, Capan-1 and BxPC-3 cells have anti-proliferative abilities, with GI50 values of 1.3, 1.4, 5.9 and 2.6 nM, respectively. Cell viability assay [1] Cell Types: PANC-1 Cell Tested Concentrations: 0, 100, 400 and 800 nM Incubation Duration: 6 and 24 hrs (hours) Experimental Results: Binding to hTERT G4 and HuTel21 G4, KD values were 4.9 and 28.4 nM respectively. Cell viability assay[1] Cell Types: MIA PaCa-2 Cell Tested Concentrations: 40 nM Incubation Duration: 6 hrs (hours) and 24 hrs (hours) Experimental Results: WNT5B, DVL1, AXIN and APC2 expression were affected, including the Wnt/β-catenin pathway, and on Axon guidance, Hippo, MAPK and Rap1 pathways. For in vitro cell proliferation assays, human pancreatic cancer cell lines (MIA PaCa-2, PANC-1, Capan-1, BxPC-3) are seeded in 96-well plates at 3 × 10^3 cells/well and allowed to attach overnight. Cells are then treated with varying concentrations of SOP-1812 (0-50 nM) for 96 hours. Cell viability is measured using the CellTiter-Glo luminescent assay or by MTT assay. The growth inhibition (GI50) value, representing the concentration required to inhibit cell growth by 50%, is calculated from dose-response curves. For confirmation of mechanism, cells are treated with 40 nM SOP-1812 for 6 or 24 hours, and total RNA is extracted for RNA-seq or qPCR analysis of target genes (WNT5B, DVL1, AXIN, APC2). Protein lysates are analyzed by Western blotting for markers of the Wnt/beta-catenin, Hippo, MAPK, and Rap1 pathways. |
| Animal Protocol |
Animal/Disease Models: Female athymic nude mice using MIA PaCa-2 xenografts [1]
Doses: 1 mg/kg Route of Administration: intravenous (iv) (iv)injection; 1 mg/kg once or twice weekly; 28-day Experimental Results: Day 28 After several days, several animals had complete tumor regression with no obvious tumor regrowth. Animal/Disease Models: KPC mice with PDAC symptoms [1] Doses: 1 mg/kg Route of Administration: intravenous (iv) (iv)injection; 1 mg/kg, once a week; 3 consecutive weeks Experimental Results: Dramatically prolonged the survival of KPC mice, And the effect is better than gemcitabine. For in vivo animal studies, a mouse xenograft model of pancreatic cancer is used. Female athymic nude mice (6-8 weeks old, n=8-10 per group) are subcutaneously injected with 5 × 10^6 MIA PaCa-2 cells suspended in PBS/Matrigel (1:1). When tumors reach an average volume of 100-150 mm3 (approximately day 7-10 post-inoculation), mice are randomly assigned to treatment groups. SOP-1812 is administered intravenously via tail vein injection at a dose of 1 mg/kg, either once weekly (Q7D) or twice weekly (Q3-4D), for a total of 4 weeks (28 days). Control animals receive vehicle (e.g., saline or 5% DMSO in PBS). Tumor volumes are measured every 2-3 days using calipers, calculated as (length × width2)/2. Body weight is monitored as a measure of tolerability. At the study endpoint (day 28), tumors are excised, weighed, and analyzed for histological markers (Ki-67 for proliferation, cleaved caspase-3 for apoptosis) by immunohistochemistry. Complete tumor regression is defined as no palpable tumor on day 28. For survival studies in the KPC model (a genetically engineered mouse model of PDAC), KPC mice are treated with SOP-1812 (1 mg/kg IV, once weekly for 3 weeks), and survival is monitored over time. |
| ADME/Pharmacokinetics |
Detailed pharmacokinetic data for SOP-1812 is limited. The compound has a molecular weight of 791.98 g/mol, which is relatively high, and is administered intravenously in preclinical studies, indicating poor oral bioavailability. The effective dose in mouse models is 1 mg/kg (IV). Following IV administration, the compound is likely distributed into tissues, including tumors, due to its affinity for G4 DNA structures. The terminal half-life is estimated to be 6-12 hours based on its large molecular size and the prolonged anti-tumor effects observed (tumor regression lasting beyond the dosing period). The compound is soluble in DMSO and can be formulated with saline for IV administration.
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| Toxicity/Toxicokinetics |
Formal toxicology data for SOP-1812 is not publicly available. In cell culture studies, the compound exhibits potent anti-proliferative activity at low nanomolar concentrations (GI50 1-6 nM). However, at concentrations up to 50 nM, it does not cause immediate cytotoxicity; rather, it induces sustained growth inhibition and eventual tumor regression in vivo. In animal studies, SOP-1812 appears to be well tolerated at the efficacious dose of 1 mg/kg (IV, weekly), with no reported deaths or significant body weight loss in the treated animals. No specific information on organ toxicity, genotoxicity, or reproductive toxicity is available. The compound is not approved for human use.
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| References | |
| Additional Infomation |
QN-302 is a naphthalimide (ND) derivative and a selective G-quadruplex (G4) transcription inhibitor with potential antitumor activity. After administration, QN-302 targets and binds to highly stable G-quadruplex DNA sequences ubiquitously present in the promoter regions of cancer-related genes, further stabilizing these complexes. This stabilizing effect prevents G-quadruplex unwinding and inhibits transcription factor binding, thereby suppressing the transcription and expression of target genes and reducing the proliferation of G4-expressing cancer cells. Specifically, QN-302 downregulates the expression of the S100P gene in tumor cells. S100P forms numerous quadruplex sequences, plays a crucial role in the proliferation and migration pathways of various cancers, and is highly expressed in multiple tumor cell types. The G4 sequence is overexpressed in the promoter regions of many oncogenes.
SOP-1812 is a research compound and is not approved for clinical use. It is also known as QN-302 and is a selective G-quadruplex (G4) transcription inhibitor that targets G4 structures in the promoter regions of cancer-related genes, thereby downregulating multiple oncogenic signaling pathways simultaneously. This multi-pathway targeting approach is particularly relevant for cancers with complex genetic heterogeneity, such as pancreatic cancer. SOP-1812 has been evaluated in preclinical models of pancreatic ductal adenocarcinoma (PDAC), one of the most lethal cancers, and has shown remarkable efficacy, including complete tumor regression in some xenograft models. This compound is for research use only. |
| Molecular Formula |
C45H57N7O6
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|---|---|
| Molecular Weight |
791.977391004562
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| Exact Mass |
791.437
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| CAS # |
2546091-70-5
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| PubChem CID |
155318440
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| Appearance |
Brown to reddish brown solid powder
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| LogP |
1
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
11
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| Rotatable Bond Count |
14
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| Heavy Atom Count |
58
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| Complexity |
1800
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| Defined Atom Stereocenter Count |
0
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| SMILES |
OC1=C2C=C(C3C=CC(=CC=3)CN3CCCC3)C3C(N(CCCN4CCOCC4)C(C4=C/C(/C(C(N1CCCN1CCOCC1)=O)=C2C=34)=N\CCN1CCCC1)=O)=O
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| InChi Key |
TZQVPFRBHPQZNM-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C45H57N7O6/c53-42-35-29-34(33-9-7-32(8-10-33)31-50-14-3-4-15-50)40-38-36(43(54)51(44(40)55)18-5-16-48-21-25-57-26-22-48)30-37(46-11-20-47-12-1-2-13-47)41(39(35)38)45(56)52(42)19-6-17-49-23-27-58-28-24-49/h7-10,29-30,53H,1-6,11-28,31H2
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| Chemical Name |
14-hydroxy-6,13-bis(3-morpholin-4-ylpropyl)-10-(2-pyrrolidin-1-ylethylimino)-3-[4-(pyrrolidin-1-ylmethyl)phenyl]-6,13-diazatetracyclo[6.6.2.04,16.011,15]hexadeca-1(14),2,4(16),8,11(15)-pentaene-5,7,12-trione
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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 |
| 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) |
DMSO : ~200 mg/mL (~252.53 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.2627 mL | 6.3133 mL | 12.6266 mL | |
| 5 mM | 0.2525 mL | 1.2627 mL | 2.5253 mL | |
| 10 mM | 0.1263 mL | 0.6313 mL | 1.2627 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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