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| Targets |
DCZ3301 targets multiple cellular pathways critical for cancer cell survival and proliferation. Its primary mechanism involves inhibiting the PI3K/AKT signaling pathway by downregulating PI3K protein expression and reducing AKT phosphorylation. This pathway is frequently hyperactivated in various cancers, including multiple myeloma and T-cell leukemia, making it a validated therapeutic target. Additionally, DCZ3301 induces DNA damage and mitotic catastrophe by inhibiting DNA repair pathways, particularly homologous recombination, and activating the ATM/ATR-CHK1 signaling axis. The compound also targets mitochondrial function by decreasing mitochondrial membrane potential (MMP), which triggers the intrinsic apoptotic pathway. This multi-targeting approach may contribute to its effectiveness against drug-resistant cancer cells, including those resistant to bortezomib. The combination of PI3K/AKT inhibition, DNA damage induction, and mitochondrial disruption makes DCZ3301 a unique and potentially more effective anticancer agent compared to single-target inhibitors.
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| ln Vitro |
DCZ3301 demonstrates potent in vitro activity across multiple cancer cell lines. It effectively inhibits cell proliferation and induces G2/M cell cycle arrest in various cancer models. In T-cell leukemia/lymphoma cells, DCZ3301 induces apoptosis by decreasing mitochondrial membrane potential (MMP). The compound shows potent cytotoxic activity against multiple myeloma (MM) cells, including those resistant to bortezomib (BTZ), with its primary mechanism involving the induction of DNA damage and mitotic catastrophe. DCZ3301 inhibits the activation of the PI3K/AKT pathway by downregulating PI3K protein expression and phosphorylation of AKT. The compound's ability to overcome BTZ resistance is particularly noteworthy, as it suggests a distinct mechanism of action from proteasome inhibitors. The in vitro potency of DCZ3301, combined with its multi-targeted mechanism, makes it a valuable tool for studying cancer biology and evaluating potential therapeutic strategies.
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| ln Vivo |
In vivo activity data for DCZ3301 is limited in the publicly available literature. As a potent aryl-guanidino inhibitor with demonstrated in vitro efficacy against multiple myeloma and T-cell leukemia/lymphoma, the compound would be expected to exhibit antitumor activity in appropriate animal models. Based on its mechanism of action—inhibiting the PI3K/AKT pathway, inducing DNA damage, and activating the ATM/ATR-CHK1 signaling axis—DCZ3301 would likely suppress tumor growth in xenograft models of hematological malignancies. Its ability to overcome bortezomib resistance in vitro suggests potential efficacy in drug-resistant tumor models in vivo. However, comprehensive in vivo efficacy studies, including pharmacokinetic and pharmacodynamic evaluations, have not been extensively reported. Further preclinical studies in appropriate mouse models would be necessary to fully characterize the compound's antitumor activity, optimal dosing regimens, and therapeutic window before considering advancement to clinical trials.
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| Enzyme Assay |
In vitro enzyme/receptor binding assays for DCZ3301 typically focus on evaluating its effects on key signaling pathways rather than direct enzyme inhibition. The compound's activity is commonly assessed using Western blot analysis to measure protein expression levels of PI3K and phosphorylation of AKT in treated cancer cells. Additionally, DNA damage and repair pathway activation can be evaluated by assessing phosphorylation of ATM, ATR, and CHK1 using phospho-specific antibodies. Cell cycle analysis via flow cytometry is employed to confirm G2/M arrest, while apoptosis is quantified using Annexin V/PI staining or caspase activity assays. Mitochondrial membrane potential (MMP) can be measured using fluorescent dyes such as JC-1 to assess the compound's effect on mitochondrial function. These assays provide comprehensive mechanistic insights into DCZ3301's multi-targeted anticancer activity.
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| Cell Assay |
In vitro cell-based assays for DCZ3301 are designed to evaluate its antiproliferative, pro-apoptotic, and cell cycle effects in various cancer cell lines. Multiple myeloma cell lines (including bortezomib-sensitive and -resistant strains) and T-cell leukemia/lymphoma cells are commonly used. Cells are treated with varying concentrations of DCZ3301 for 24-72 hours, and cell viability is assessed using MTT, CCK-8, or CellTiter-Glo assays to determine IC₅₀ values. Cell cycle distribution is analyzed by flow cytometry following propidium iodide staining to confirm G2/M arrest. Apoptosis is quantified using Annexin V-FITC/PI double staining or caspase-3/7 activity assays. Mitochondrial membrane potential is measured using JC-1 dye to assess mitochondrial dysfunction. PI3K/AKT pathway inhibition is confirmed by Western blot analysis of PI3K and phosphorylated AKT levels.
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| Animal Protocol |
In vivo animal study protocols for DCZ3301 are not extensively documented in the publicly available literature. Based on standard practices for evaluating similar anticancer agents, potential in vivo studies would involve subcutaneous xenograft mouse models using multiple myeloma or T-cell leukemia/lymphoma cell lines. Tumor-bearing mice would be randomized into treatment groups receiving DCZ3301 at various doses via intraperitoneal or oral administration. Tumor volume and body weight would be monitored regularly to assess efficacy and tolerability. At study endpoint, tumors would be harvested for immunohistochemical analysis of PI3K/AKT pathway markers, DNA damage markers (γH2AX), and apoptosis markers (cleaved caspase-3). Pharmacodynamic markers such as phosphorylated AKT and CHK1 would be assessed to confirm target engagement. These studies would be essential for determining the compound's in vivo efficacy, optimal dosing schedule, and therapeutic window.
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| ADME/Pharmacokinetics |
Detailed pharmacokinetic (PK) data for DCZ3301 is not extensively reported in the publicly available literature. As a small-molecule aryl-guanidino inhibitor with a molecular weight suitable for drug development, the compound is expected to have reasonable drug-like properties. Based on its chemical structure, DCZ3301 would likely be formulated for oral or intraperitoneal administration in preclinical studies. Comprehensive PK parameters such as half-life (t½), maximum plasma concentration (Cmax), area under the curve (AUC), oral bioavailability, and volume of distribution would need to be determined through dedicated pharmacokinetic studies. Tissue distribution studies would be important to assess the compound's ability to reach target tissues, particularly bone marrow where hematological malignancies reside. Metabolic stability and protein binding studies would also be necessary to fully characterize the compound's ADME (Absorption, Distribution, Metabolism, Excretion) profile.
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| Toxicity/Toxicokinetics |
Specific toxicity data for DCZ3301 is not extensively reported in the publicly available literature. As a potent anticancer agent targeting the PI3K/AKT pathway, inducing DNA damage, and disrupting mitochondrial function, the compound would be expected to have significant cytotoxic effects on rapidly dividing cells. This on-target activity could result in dose-limiting toxicities affecting bone marrow, gastrointestinal epithelium, and other proliferating tissues. The compound's ability to overcome bortezomib resistance suggests a distinct mechanism that may have a different toxicity profile from proteasome inhibitors. Comprehensive preclinical toxicology studies, including assessments of genotoxicity, acute and chronic toxicity, and effects on major organ systems, would be required before clinical development. The compound is currently classified as a research-grade chemical and is not intended for human use.
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| References | |
| Additional Infomation |
DCZ3301 is a potent aryl-guanidino inhibitor with multi-targeted anticancer activity against multiple myeloma and T-cell leukemia/lymphoma. Its mechanism involves PI3K/AKT pathway inhibition, DNA damage induction via ATM/ATR-CHK1 activation, and mitochondrial disruption leading to apoptosis. The compound demonstrates activity against bortezomib-resistant multiple myeloma cells, suggesting potential for overcoming drug resistance. DCZ3301 effectively inhibits cell proliferation, induces G2/M cell cycle arrest, and facilitates apoptosis in cancer cells. As a research-grade compound, it is intended for laboratory use only and has not yet advanced to clinical trials or received FDA approval. Further preclinical development, including comprehensive in vivo efficacy and toxicology studies, would be necessary to evaluate its therapeutic potential.
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| Exact Mass |
464.0975
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| CAS # |
2136278-38-9
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| Appearance |
White to off-white solid powder
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| Synonyms |
DCZ3301; DCZ3301; DCZ3301
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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.) |
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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