| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| 250mg | |||
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| Targets |
The precise molecular target of RTC-5 is not a single kinase. It acts through a novel mechanism, putatively involving the activation of the tumor suppressor Protein Phosphatase 2A (PP2A). This leads to the concomitant negative regulation of the PI3K-AKT and RAS-ERK signaling pathways [1].
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| ln Vitro |
RTC-5 (0-40 μM; 48 hours) blocks H1650 lung cancer cells from growing, having a GI50 of 12.6 μM [1]. By decreasing the expression of phospho-AKT and phospho-ERK levels, RTC-5 (20–40 μM; 24 hours) negatively affects the PI3K-AKT and RAS-ERK pathways [1].
RTC-5 exhibited anti-proliferative activity in an MTT cell viability assay using H1650 lung adenocarcinoma cells, with a GI50 of 12.6 µM [1]. Treatment with RTC-5 induced a dose-dependent accumulation of cells in the sub-G1 phase and cell cycle arrest, effects that were more pronounced than those induced by the parent compounds trifluoperazine (TFP) or clomipramine (CIP) [1]. RTC-5 induced apoptosis, as confirmed by an increase in Annexin V staining. This apoptotic effect was reversed by co-treatment with the pan-caspase inhibitor Z-VAD, indicating that apoptosis is caspase-mediated [1]. Western blot analysis demonstrated that RTC-5 treatment negatively regulates both the PI3K-AKT and RAS-ERK pathways, as indicated by decreased levels of phospho-AKT and phospho-ERK in H1650 cells [1]. A DiscoverRx kinome screen confirmed that RTC-5 does not inhibit any relevant kinase in an ATP-competitive manner [1]. In radioligand binding assays, RTC-5 showed negligible binding to the serotonin transporter (5-HTT, <5% inhibition at 0.1 mM). It exhibited weak binding to the dopamine transporter (DT) and norepinephrine transporter (NET) only at elevated concentrations (1.0 and 10 mM) [1]. RTC-5 did not show significant binding to a panel of dopamine receptor subtypes (D1-D5) or most serotonin receptor subtypes, except for some residual binding at 5-HT5A at high concentrations (24% at 1.0 mM, 68% at 10 mM) [1]. |
| ln Vivo |
In a xenograft study using the H1650 lung cancer cell line in mice, treatment with RTC-5 at 100 mg/kg caused a statistically significant decrease in the mean fold change in tumor volume (1.49 ± 0.26, n=9) compared to the vehicle control group (3.46 ± 0.95, n=7) (p < 0.004, Student's t-test). In contrast, the parent compound TFP could not be dosed higher than 10 mg/kg in the same study due to marked central nervous system (CNS) side effects [1].
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| Cell Assay |
Cell viability assay [1]
Cell Types: H1650 lung adenocarcinoma cells Tested Concentrations: 0 μM, 1 μM, 10 μM, 20 μM, 30 μM, 40 μM Incubation Duration: 48 hrs (hours) Experimental Results: Inhibition of the growth of H1650 lung adenocarcinoma cells. Western Blot Analysis[1] Cell Types: H1650 lung adenocarcinoma cells Tested Concentrations: 20 μM, 40 μM Incubation Duration: 24 hrs (hours) Experimental Results: diminished expression of p-AKT, p-ERK. |
| ADME/Pharmacokinetics |
In pharmacokinetic studies in mice, RTC-5 showed significant absorption (34-38%) via intraperitoneal injection (IP) and moderate oral absorption (15-18%). It exhibited moderate clearance (42 ml/min/kg) and a half-life (t1/2) of 0.61 hours [1].
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| Toxicity/Toxicokinetics |
RTC-5 binds negligibly to multiple receptors (M2, H1, H2, hERG) located in cardiac tissue and associated with QT interval prolongation [1]. RTC-5 does not bind to multiple calcium-potassium channels associated with cardiovascular disease [1]. In patch-clamp experiments, RTC-5 has a negligible effect on the voltage-gated sodium channel Nav1.5 compared to clomipramine (CIP) [1].
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| References | |
| Additional Infomation |
RTC-5 is a modified tricyclic compound, specifically a dibenzozazepine derivative in which the basic dimethylamine side chain of its parent antipsychotic drug is replaced by a neutral polar sulfonamide functional group (4-trifluoromethoxybenzenesulfonamide linked by a three-carbon chain). This key modification aims to eliminate the central nervous system-related pharmacological effects of the parent molecule (e.g., dopamine receptor antagonism) while preserving and optimizing its anticancer "side effects" [1]. The anticancer effect of RTC-5 is attributed to a novel mechanism involving the activation of the tumor-suppressing protein phosphatase PP2A, leading to dual negative regulation of the oncogenic PI3K-AKT and RAS-ERK signaling pathways. This distinguishes it from classic kinase inhibitors [1].
RTC-5 demonstrated in vivo efficacy in an EGFR-driven lung cancer xenograft model and did not show significant neurotrophic (sedative, extrapyramidal) effects that severely limit the dosage of the parent tricyclic drug in animal models and humans [1]. |
| Molecular Formula |
C24H22CLF3N2O3S
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|---|---|
| Molecular Weight |
510.956294536591
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| Exact Mass |
510.099
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| CAS # |
1423077-49-9
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| PubChem CID |
71263344
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| Appearance |
White to off-white solid powder
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| LogP |
7
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
34
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| Complexity |
756
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1C=CC2CCC3C=CC=CC=3N(C=2C=1)CCCNS(C1C=CC(=CC=1)OC(F)(F)F)(=O)=O
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| InChi Key |
QYOJMNDDVVEPFN-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C24H22ClF3N2O3S/c25-19-9-8-18-7-6-17-4-1-2-5-22(17)30(23(18)16-19)15-3-14-29-34(31,32)21-12-10-20(11-13-21)33-24(26,27)28/h1-2,4-5,8-13,16,29H,3,6-7,14-15H2
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| Chemical Name |
N-[3-(2-chloro-5,6-dihydrobenzo[b][1]benzazepin-11-yl)propyl]-4-(trifluoromethoxy)benzenesulfonamide
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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 : ~15 mg/mL (~29.36 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.5 mg/mL (2.94 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 15.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 1.5 mg/mL (2.94 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 15.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9571 mL | 9.7855 mL | 19.5710 mL | |
| 5 mM | 0.3914 mL | 1.9571 mL | 3.9142 mL | |
| 10 mM | 0.1957 mL | 0.9786 mL | 1.9571 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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