| Size | Price | Stock | Qty |
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| 5mg |
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| Other Sizes |
| Targets |
The study suggests a possible role as an inhibitor of signal transduction, as it inhibits mitogen-induced DNA synthesis. PAF receptors were ruled out as a target. [1]
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| ln Vitro |
SDZ-62-434 exhibited antiproliferative activity against a range of human tumor cell lines, including both solid and hematological malignancies, with IC₅₀ values ranging from 3.6 μM to 111 μM after a 24-hour exposure, as measured by the MTT assay. The HT29 colon adenocarcinoma line was most sensitive (IC₅₀ = 5.1 μM), while the MCF-7 breast carcinoma line was most resistant (IC₅₀ = 111 μM). Similar IC₅₀ values were obtained using a clonogenic assay. [1]
In A2780 ovarian carcinoma cells, SDZ-62-434 inhibited cell growth in a concentration- and time-dependent manner. A 24-hour exposure to 10 μM caused a growth delay, while continuous exposure led to a more pronounced growth inhibition and a decrease in cell number after 96 hours. The potency increased with exposure time up to 48 hours. [1] In A2780 cells, SDZ-62-434 inhibited DNA synthesis (measured by [³H]thymidine incorporation) more effectively than protein synthesis, while RNA synthesis was largely unaffected. The IC₅₀ for inhibition of DNA synthesis was approximately 34 μM. [1] In drug-resistant variants, a 2-3 fold cross-resistance to SDZ-62-434 was observed in doxorubicin-resistant (A2780/AD) and cisplatin-resistant (A2780/CP) ovarian carcinoma cells. No cross-resistance was seen in a doxorubicin-resistant MCF-7 variant (MCF-7/AD). SDZ-62-434 did not modulate the cytotoxicity of doxorubicin in either parent or resistant A2780 cells. [1] SDZ-62-434 did not cause significant membrane lysis in A2780 or HT29 cells at concentrations up to 200 μM, as measured by a ⁵¹Cr release assay. At its IC₅₀, specific lysis was ≤4%. [1] The potent PAF antagonist WEB 2086 (up to 100 μM) did not modulate the cytotoxicity of SDZ-62-434 in A2780 cells, indicating that its mechanism of action is not mediated through PAF receptors. [1] In quiescent Swiss 3T3 cells, SDZ-62-434 (10 μM) inhibited DNA synthesis stimulated by platelet-derived growth factor (PDGF) and bombesin by 50% and 86%, respectively. It also inhibited serum-stimulated mitogenesis by 61%. This suggests a possible role for SDZ-62-434 as an inhibitor of signal transduction pathways. [1] |
| Cell Assay |
MTT Cytotoxicity Assay: Cells were seeded in 96-well plates and grown for 72 hours. They were then exposed to a range of concentrations of SDZ-62-434 for 24 hours. The drug was removed, and fresh medium was added for a further 3 days to allow cell growth. MTT reagent was added, and after 4 hours, the formazan crystals were dissolved. Absorbance was read at 570 nm. IC₅₀ values were determined from log-concentration response curves. [1]
Clonogenic Assay: Cells were exposed to SDZ-62-434 for 24 hours, then harvested, counted, and plated at low density in drug-free medium. After 10 days, colonies (>50 cells) were fixed, stained, and counted. IC₅₀ values were determined from log-concentration response curves. [1] Radiolabel Incorporation (DNA/RNA/Protein Synthesis): A2780 cells were exposed to SDZ-62-434 for 24 hours. [³H]thymidine, [³H]uridine, or [³H]leucine was added for the final hour. Cells were washed, extracted with perchloric acid, and solubilized. Radioactivity was measured by liquid scintillation counting and normalized to protein content. [1] ⁵¹Cr Release Assay (Membrane Lysis): A2780 or HT29 cells were labeled with Na₂⁵¹CrO₄, washed, and seeded in 96-well plates. They were exposed to SDZ-62-434 for 4 hours. Supernatant was collected, and radioactivity was measured. Percent specific lysis was calculated relative to spontaneous and maximum (Triton X-100) release. [1] Mitogenesis Assay (Swiss 3T3 Cells): Quiescent Swiss 3T3 cells were stimulated with PDGF, bombesin, or serum in the presence or absence of SDZ-62-434 (10 μM). [³H]thymidine was added for 40 hours. Incorporation into acid-insoluble material was measured as an indicator of DNA synthesis. [1] |
| References | |
| Additional Infomation |
SDZ-62-434 is a novel imidazoisoquinoline originally identified as a platelet-activating factor (PAF) antagonist. It was selected for clinical evaluation based on its in vitro cytotoxicity and novel structure and has entered a Phase 1 trial in the UK under the Cancer Research Campaign. [1]
Its mechanism of antitumor action was not well understood at the time of this study. This work demonstrates that its cytotoxicity is not mediated by PAF receptors and is not due to non-specific membrane lysis. The compound preferentially inhibits DNA synthesis and can block mitogenic signaling induced by both a receptor tyrosine kinase (PDGF) and a G-protein-coupled receptor (bombesin) agonist, suggesting it may act on a convergent downstream point in signal transduction pathways. [1] The study shows a wide range of sensitivities across different tumor types, with colon cancer cells being particularly sensitive and breast cancer cells being relatively resistant. Partial cross-resistance was observed in some drug-resistant ovarian cancer lines but not in a resistant breast cancer line. [1] |
| Molecular Formula |
C22H25CL2N3
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|---|---|
| Molecular Weight |
402.363
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| Exact Mass |
401.143
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| CAS # |
115621-95-9
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| Related CAS # |
115621-95-9 (HCl);115621-81-3 (free);
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| PubChem CID |
130786
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| Appearance |
Typically exists as solid at room temperature
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| Boiling Point |
520.3ºC at 760 mmHg
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| Flash Point |
268.5ºC
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| Vapour Pressure |
6.3E-11mmHg at 25°C
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| LogP |
5.317
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
27
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| Complexity |
538
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| Defined Atom Stereocenter Count |
0
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| SMILES |
Cl.Cl.C1CCN(C2=CC=C(C3=CC4=CC=CC=C4C4=NCCN34)C=C2)CC1
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| InChi Key |
BKOQATFPPHQOQH-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H23N3.2ClH/c1-4-13-24(14-5-1)19-10-8-17(9-11-19)21-16-18-6-2-3-7-20(18)22-23-12-15-25(21)22;;/h2-3,6-11,16H,1,4-5,12-15H2;2*1H
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| Chemical Name |
5-(4-piperidin-1-ylphenyl)-2,3-dihydroimidazo[2,1-a]isoquinoline;dihydrochloride
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| Synonyms |
SDZ 62 434 SDZ62434 SDZ-62-434
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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 | 2.4853 mL | 12.4267 mL | 24.8534 mL | |
| 5 mM | 0.4971 mL | 2.4853 mL | 4.9707 mL | |
| 10 mM | 0.2485 mL | 1.2427 mL | 2.4853 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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