| Size | Price | Stock | Qty |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg | |||
| Other Sizes |
Purity: ≥98%
| Targets |
ROC-325 targets lysosomal-mediated autophagy. It causes lysosomal deacidification, leading to the accumulation of autophagosomes and disruption of autophagic flux. By inhibiting this key cellular recycling process, ROC-325 induces apoptosis in cancer cells, particularly in renal cell carcinoma, and exhibits favorable selectivity. Its mechanism of action is distinct from other autophagy inhibitors, as it interferes with the late stages of the autophagic process at the lysosomal level.
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| ln Vitro |
Renal cell carcinoma (RCC) development and activation are inhibited by ROC-325 in an antagonistic way towards ATG5/7, resulting in cell apoptosis and excellent selectivity. A498, A549, CFPAC-1, COLO -205, DLD-1, IGROV-1, MCF-7, MiaPaCa-2, NCI-H69, PC-3, RL, and UACC-62 cells are all inhibited by ROC-325; the IC50 values for these cells are 4.9 μM, 11 μM, 4.6 μM, 5.4 μM, 7.4 μM, 11 μM, 8.2 μM, 5.8 μM, 11 μM, 8.4 μM, and 6.0 μM. Autophagy labeling is induced by ROC-325, which also counteracts autophagy staining [1]. Tissue stain D (CTSD) levels were increased in response to ROC-325. After subjecting A498 and 786-0 RCC cells to a 24-hour treatment with 5 μM ROC-325, LC3B solution was formed and LC3B levels dramatically increased. ROC-325 facilitated dose-increasing LC3B expression in A498 and 786-0 cells, according to immunoblot analysis, which was correlated with increases in p62 and histone D levels [1].
In vitro, ROC-325 has demonstrated superior anticancer effects compared to hydroxychloroquine (HCQ) across 12 different cancer cell lines with diverse genetic backgrounds. It diminishes AML cell viability with an IC50 range of 0.7-2.2 μM. The compound causes lysosomal deacidification, accumulation of autophagosomes, and disruption of autophagic flux. It induces apoptosis in renal cell carcinoma cells and exhibits favorable selectivity. ROC-325 shows potent anticancer activity in various cancer types. |
| ln Vivo |
suggested that ROC-325 (25 mg/kg, 40 mg/kg, and 50 mg/kg) applied to the anatomical surface of 786-0 RCC xenografts was well tolerated, inhibited autophagy in the body, and was more effective at halting tumor growth in vitro than chemotherapy[1].
In vivo, oral administration of ROC-325 to mice bearing renal cell carcinoma (RCC) xenografts is well tolerated and yields dose-dependent inhibition of tumor growth that is significantly more efficacious than a higher dose of HCQ. No notable toxicities are observed other than a modest, non-significant, reversible reduction in mean body weight. These results highlight its potential as a therapeutic agent for cancers dependent on autophagy for survival. |
| Enzyme Assay |
Cell-free assays for ROC-325 are not standard as it is an autophagy inhibitor. Its activity is primarily assessed in cellular systems. However, its ability to bind to its target can be studied using techniques like surface plasmon resonance. The compound's purity is confirmed by HPLC (>98%). Its molecular weight and formula are established. Its solubility in DMSO (32 mg/mL) is documented.
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| Cell Assay |
In vitro cellular assays measure the viability of cancer cell lines after treatment with ROC-325. AML cell viability is assessed with an IC50 range of 0.7-2.2 μM. The compound's effect on autophagy is measured by assessing lysosomal deacidification, autophagosome accumulation, and disruption of autophagic flux. Apoptosis is evaluated in renal cell carcinoma cells. Its anticancer effects are compared to hydroxychloroquine (HCQ) across 12 different cancer cell lines.
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| Animal Protocol |
In vivo animal experiments for ROC-325 involve mouse models bearing RCC xenografts. Oral administration is used to assess dose-dependent inhibition of tumor growth. The compound's tolerability is evaluated by monitoring body weight and overall health. Its efficacy is compared to that of hydroxychloroquine (HCQ). These studies are crucial for determining the in vivo anticancer activity and safety profile of the compound.
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| ADME/Pharmacokinetics |
ROC-325 has a molecular weight of 503.061 and a molecular formula of C28H27ClN4OS. It is an orally bioavailable compound. It is soluble in DMSO at 32 mg/mL and has a purity >98% (HPLC). In vivo, it is formulated as a homogeneous suspension for oral administration. The compound is stable as a powder at -20°C for up to three years.
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| Toxicity/Toxicokinetics |
The toxicological profile of ROC-325 appears favorable based on in vivo studies. In mouse xenograft models, oral administration of ROC-325 is well tolerated. No notable toxicities are observed other than a modest, non-significant, reversible reduction in mean body weight. This suggests that ROC-325 has a better safety profile compared to hydroxychloroquine, especially at therapeutically relevant doses.
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| References | |
| Additional Infomation |
hydroxychloroquine derivative that inhibits autophagy and has antitumor properties.
ROC-325 is a novel, potent, and orally bioactive inhibitor of lysosomal-mediated autophagy. It has potent anticancer activity and exhibited superior in vitro anticancer effects compared to hydroxychloroquine (HCQ) in 12 different cancer cell lines. In vivo, it is well tolerated and yields dose-dependent inhibition of tumor growth. ROC-325 is a research compound not yet approved for clinical use. |
| Molecular Formula |
C28H27CLN4OS
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| Molecular Weight |
503.0582
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| Exact Mass |
502.159
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| CAS # |
1859141-26-6
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| Related CAS # |
1859141-26-6
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| PubChem CID |
129626603
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| Appearance |
Light yellow to orange solid powder
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| LogP |
7
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
35
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| Complexity |
712
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1C=CC2C(C=1)=NC=CC=2NCCN(C)CCNC1C=CC(C)=C2C=1C(C1=CC=CC=C1S2)=O
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| InChi Key |
HXUYKEGAEIYPKY-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C28H27ClN4OS/c1-18-7-10-23(26-27(34)21-5-3-4-6-25(21)35-28(18)26)32-14-16-33(2)15-13-31-22-11-12-30-24-17-19(29)8-9-20(22)24/h3-12,17,32H,13-16H2,1-2H3,(H,30,31)
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| Chemical Name |
1-((2-((2-((7-chloroquinolin-4-yl)amino)ethyl)(methyl)amino)ethyl)amino)-4-methyl-9H-thioxanthen-9-one
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| Synonyms |
ROC-325 ROC 325 ROC325.
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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 : ~4.55 mg/mL (~9.04 mM)
H2O : ~1 mg/mL (~1.99 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 | 1.9878 mL | 9.9392 mL | 19.8783 mL | |
| 5 mM | 0.3976 mL | 1.9878 mL | 3.9757 mL | |
| 10 mM | 0.1988 mL | 0.9939 mL | 1.9878 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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