DpC
Based on 1 Customer Validation
DpC is an orally active iron chelator and anticancer agent. DpC induces lysosomal membrane permeabilization, redox-active iron/copper complex formation, oxidative stress, and Apoptosis through carrier/receptor-mediated uptake and Pgp-mediated lysosomal transport, while upregulating NDRG1 to inhibit oncogenic signaling and tumor progression, and modulates pathways such as JNK, IκBα/NF-κB, c-Src, and EGFR/HER2/HER3. DpC selectively inhibits tumor cell proliferation and can be used in research on neuroblastoma, kidney disease, prostate cancer, and pancreatic cancer.
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- Pureza : 98.73%
- No. CAS: 1382469-39-7
- Fòrmula: C19H23N5S
- Peso molecular:353.48
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Almacenamiento:Powder -20°C, 3 years ; In solvent -80°C, 6 months , -20°C, 1 month
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Actividad biológica
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Chemical Information
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Solvente y solubilidad
- Protocolo
- Pureza y Documentación
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Help & FAQs
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Actividad biológica
Descripciòn
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JNK |
NF-κB |
EGFR |
HER2 |
HER3 |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
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| PANC-1 | IC50 |
11.40 μM
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Antiproliferative activity of DpC against human PANC-1 pancreatic cancer cells assessed by MTT assay after 24 hrs incubation.
Antiproliferative activity of DpC against human PANC-1 pancreatic cancer cells assessed by MTT assay after 24 hrs incubation.
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35436509 |
| PANC-1 | IC50 |
0.096 μM
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Antiproliferative activity of DpC against human PANC-1 pancreatic cancer cells assessed by MTT assay after 72 hrs incubation.
Antiproliferative activity of DpC against human PANC-1 pancreatic cancer cells assessed by MTT assay after 72 hrs incubation.
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35436509 |
| PC-3 | IC50 |
17.10 μM
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Antiproliferative activity of DpC against human PC3 prostate cancer cells assessed by MTT assay after 24 hrs incubation.
Antiproliferative activity of DpC against human PC3 prostate cancer cells assessed by MTT assay after 24 hrs incubation.
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35436509 |
| PC-3 | IC50 |
0.007 μM
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Antiproliferative activity of DpC against human PC3 prostate cancer cells assessed by MTT assay after 72 hrs incubation.
Antiproliferative activity of DpC against human PC3 prostate cancer cells assessed by MTT assay after 72 hrs incubation.
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35436509 |
| DMS-53 | IC50 |
6.50 μM
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Antiproliferative activity of DpC against human DMS-53 lung cancer cells assessed by MTT assay after 24 hrs incubation.
Antiproliferative activity of DpC against human DMS-53 lung cancer cells assessed by MTT assay after 24 hrs incubation.
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35436509 |
| DMS-53 | IC50 |
0.020 μM
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Antiproliferative activity of DpC against human DMS-53 lung cancer cells assessed by MTT assay after 72 hrs incubation.
Antiproliferative activity of DpC against human DMS-53 lung cancer cells assessed by MTT assay after 72 hrs incubation.
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35436509 |
| DU-145 | IC50 |
7.90 μM
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Antiproliferative activity of DpC against human DU-145 prostate cancer cells assessed by MTT assay after 24 hrs incubation.
Antiproliferative activity of DpC against human DU-145 prostate cancer cells assessed by MTT assay after 24 hrs incubation.
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35436509 |
| DU-145 | IC50 |
0.007 μM
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Antiproliferative activity of DpC against human DU-145 prostate cancer cells assessed by MTT assay after 72 hrs incubation.
Antiproliferative activity of DpC against human DU-145 prostate cancer cells assessed by MTT assay after 72 hrs incubation.
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35436509 |
| MDA-MB-231 | IC50 |
9.40 μM
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Antiproliferative activity of DpC against human MDA-MB-231 breast cancer cells assessed by MTT assay after 24 hrs incubation.
Antiproliferative activity of DpC against human MDA-MB-231 breast cancer cells assessed by MTT assay after 24 hrs incubation.
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35436509 |
| MDA-MB-231 | IC50 |
0.008 μM
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Antiproliferative activity of DpC against human MDA-MB-231 breast cancer cells assessed by MTT assay after 72 hrs incubation.
Antiproliferative activity of DpC against human MDA-MB-231 breast cancer cells assessed by MTT assay after 72 hrs incubation.
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35436509 |
| H9c2 | IC50 |
> 250 μM
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Cytotoxicity against H9C2 cells assessed as viability reduction after 24 hrs incubation by XTT assay with IC50 > 250 μM.
Cytotoxicity against H9C2 cells assessed as viability reduction after 24 hrs incubation by XTT assay with IC50 > 250 μM.
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27678372 |
| HK-2 | IC50 |
17.27 μM
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Cytotoxicity against HK2 cells assessed as viability reduction after 24 hrs incubation by XTT assay.
Cytotoxicity against HK2 cells assessed as viability reduction after 24 hrs incubation by XTT assay.
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27678372 |
| PANC-1 | IC50 |
0.04 μM
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Antiproliferative activity against human PANC-1 cells assessed as proliferation inhibition by MTT assay after 72 hrs incubation.
Antiproliferative activity against human PANC-1 cells assessed as proliferation inhibition by MTT assay after 72 hrs incubation.
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26534963 |
| HT-29 | IC50 |
0.03 μM
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Antiproliferative activity against human HT-29 cells assessed as proliferation inhibition by MTT assay after 72 hrs incubation.
Antiproliferative activity against human HT-29 cells assessed as proliferation inhibition by MTT assay after 72 hrs incubation.
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26534963 |
| MIA PaCa-2 | IC50 |
0.04 μM
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Antiproliferative activity against human MIAPaCa-2 cells assessed as proliferation inhibition by MTT assay after 72 hrs incubation.
Antiproliferative activity against human MIAPaCa-2 cells assessed as proliferation inhibition by MTT assay after 72 hrs incubation.
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26534963 |
| HCT-116 | IC50 |
0.03 μM
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Antiproliferative activity against human HCT-116 cells assessed as proliferation inhibition by MTT assay after 72 hrs incubation.
Antiproliferative activity against human HCT-116 cells assessed as proliferation inhibition by MTT assay after 72 hrs incubation.
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26534963 |
In Vitro
DpC (0.125-8 × IC50; 72 h) combined with standard drugs shows synergistic effects at a lower frequency than sequential exposure in PANC-1, PC3, DMS-53, DU-145, and MDA-MB-231 cells, and DpC combined with Dp44mT (HY-18973) exhibits antagonism in all five cell lines, with DU-145 cells showing the highest CI of 16.009[1].
DpC (25 μM; 2 h) uptake by SK-N-MC cells is temperature- and energy-dependent and is competitively inhibited by excess Dp44mT[1].
DpC (2.5-250 μM; 24 h) is highly active against SK-N-LP neuroblastoma cells (IC50 < 2.5 μM), whereas it shows much higher IC50 values against MSC (145.23 μM), MIHA (165.73 μM), HK2 (17.27 μM), and H9C2 (> 250 μM) after 24 h[2].
DpC (25 μM; 12-24 h) upregulates Cygb and Ngb in HK2 and SK-N-LP cells at 24 h, but slightly decreases their expression in MSC and H9C2 cells[2].
DpC (5 μM; 24 h) induces NDRG1 and inhibits c-Src activation at Tyr416 in DU145 cells without altering total c-Src[4].
DpC (10 µM) upregulates NDRG1 and reduces EGFR protein levels and membrane localization in PANC-1 and HT-29 cells[5].
DpC (10 µM; 24 h) decreases the activation of EGFR, HER2, and HER3 in EGF-stimulated PANC-1 and HT-29 cells, while the phosphorylated/total ratio remains unchanged[5].
DpC (10 µM; 24 h) decreases EGFR and pEGFR (Tyr-1068) in PANC-1 and HT-29 cells in an NDRG1-independent manner[5].
DpC (0.08-80 µM; 72 h) inhibits the proliferation of PANC-1, HT-29, MIAPaCa-2, and HCT-116 cells, with IC50 values of 0.04, 0.03, 0.04, and 0.03 µM, respectively[5].
DpC (10 µM; 24 h) increases NDRG1 and decreases EGFR/pEGFR (Tyr-1068) in PANC-1 and HT-29 cells; the DpC-copper complex (1 µM; 24 h) does not increase NDRG1 and has cell type-dependent effects on EGFR/pEGFR (Tyr-1068)[5].
DpC (25 μM; 24 h) increases Ngb, Cygb, cleaved caspase 3/9 and p-JNK/total JNK in SK-N-LP cells after 24 h, while decreasing IκBα[2].
DpC (25 μM; 24 h) cytotoxicity in SK-N-LP cells is partially dependent on p38, JNK, NF-κB, and caspase activity, but not on ERK[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:human neuroblastoma SK-N-LP cells and non-tumorigenic immortalized MSC, H9C2, MIHA, and HK2 cells
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Concentration:2.5, 25, and 250 μM (24 h); 25 μM (24, 48, and 72 h)
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Incubation Time:12, 24, 48, and 72 h
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Result:At 25 μM, inhibited proliferation/viability of MSC, H9C2, MIHA, HK2, and SK-N-LP cells in a time-dependent manner from 24 to 72 h.
At 2.5 μM, showed no pronounced anti-proliferative activity against the non-tumorigenic MSC, H9C2, MIHA, and HK2 cells, but inhibited SK-N-LP neuroblastoma cells.
At 25 and 250 μM, selectivity against SK-N-LP relative to non-tumorigenic cells was reduced or lost.
IC50 values after 24 h were: MSC 145.23 μM; H9C2 > 250 μM; MIHA 165.73 μM; HK2 17.27 μM; SK-N-LP < 2.5 μM.
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Cell Line:human neuroblastoma cell lines SK-N-LP, BE(2)C, SK-N-AS, and SH-SY5Y
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Concentration:25 μM
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Incubation Time:24 h
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Result:In SK-N-LP cells, produced 34.6% live, 2.99% necrotic, 35% early apoptotic, and 27.4% late apoptotic cells.
In BE(2)C cells, produced 40.2% live, 28.7% necrotic, 4.36% early apoptotic, and 26.7% late apoptotic cells.
In SK-N-AS cells, produced 22.4% live, 15% necrotic, 42.3% early apoptotic, and 20.4% late apoptotic cells.
In SH-SY5Y cells, produced 73% live, 1.56% necrotic, 22.8% early apoptotic, and 2.62% late apoptotic cells.
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Cell Line:human SK-N-LP neuroblastoma cells
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Concentration:25 μM
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Incubation Time:24 h
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Result:Increased Cygb and Ngb expression in SK-N-LP cells.
Decreased IκBα expression and increased cleaved caspase 3 and cleaved caspase 9 levels.
Increased the phosphorylated JNK/total JNK ratio while having no effect on total JNK levels.
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Cell Line:SK-N-LP neuroblastoma cells
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Concentration:25 μM
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Incubation Time:24 h (after 2 h inhibitor pre-incubation)
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Result:Pre-incubation with p38, JNK, NF-κB, or caspase inhibitors partially reduced the cytotoxicity in SK-N-LP cells.
The ERK inhibitor did not affect cytotoxicity.
The caspase inhibitor was the most effective at reducing cytotoxicity.
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Cell Line:DU145 human prostate cancer cells
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Concentration:5 μM
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Incubation Time:24 h
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Result:Increased NDRG1 protein expression relative to untreated control.
Decreased phosphorylation of c-Src at Tyr416.
Did not alter total c-Src protein levels.
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Cell Line:PANC-1 and HT-29 cells
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Concentration:10 µM
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Incubation Time:24 h
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Result:Reduced EGFR, pEGFR(Tyr-1068), pEGFR(Tyr-1086), and pEGFR(Tyr-1148) in PANC-1 and HT-29 cells.
Reduced HER2, pHER2, HER3, and pHER3 in both cell lines.
The pEGFR/EGFR, pHER2/HER2, and pHER3/HER3 ratios were not changed.
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Cell Line:PANC-1 and HT-29 cells
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Concentration:10 µM
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Incubation Time:24 h
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Result:Reduced EGFR and pEGFR(Tyr-1068) in NDRG1-silenced PANC-1 and HT-29 cells.
Reduced EGFR and pEGFR(Tyr-1068) in control siRNA-transfected cells; the reduction persisted after NDRG1 silencing.
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Cell Line:PANC-1, MIAPaCa-2, HT-29, and HCT-116 cells
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Concentration:0.08, 0.31, 1.25, 5, 20, and 80 µM
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Incubation Time:72 h
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Result:Inhibited proliferation with IC50 values of 0.04 µM in PANC-1, 0.03 µM in HT-29, 0.04 µM in MIAPaCa-2, and 0.03 µM in HCT-116 cells.
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Cell Line:PANC-1 and HT-29 cells
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Concentration:10 µM (DpC); 1 µM (DpC-copper complex)
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Incubation Time:24 h (DpC and DpC-copper complex)
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Result:At 10 µM, increased NDRG1 and decreased EGFR and pEGFR(Tyr-1068) in PANC-1 and HT-29 cells.
At 1 µM, the copper complex did not significantly affect NDRG1 levels; the copper complex had no significant effect on EGFR or pEGFR(Tyr-1068) in PANC-1 cells but decreased both in HT-29 cells.
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:BALB/c nu/nu nude (male, 4 weeks old)[2]
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Dosage:4 mg/kg/day
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Administration:i.v. (tail vein); daily; 3 weeks
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Result:In vivo tumor imaging ROI value and tumor volume were reduced relative to vehicle control.
In post-mortem tumor tissue, live tumor cells were 50.9% versus 97.1% in controls; early apoptotic tumor cells were 28.2% versus 0.59%; late apoptotic tumor cells were 14.2% versus 1.15%.
Caspase 3 levels were higher in tumor tissue.
H&E staining confirmed neuroblastoma xenograft regression.
SK-N-LP tumor xenografts showed higher TNFα levels; IFNγ was slightly increased and IL-10 slightly decreased.
Xenograft tissues also showed higher neuroglobin, cytoglobin, caspase 3, and TNFα levels, with a slight decrease in IL-10.
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Animal Model:BALB/c nu/nu nude (female, 8 weeks old)[5]
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Dosage:5 mg/kg (as DpC HCl)
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Administration:i.v. via tail vein; 5 days/week (Monday to Friday); for 23 days
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Result:After 23 days, decreased PANC-1 tumor growth to 19.3% of control (n = 6).
Tumor size at day 23 was comparable to day 0.
Tumors had ImmunoMembrane classification scores of 0.5 for EGFR, 2 for HER2, and 0.7 for HER3.
- Annexin V plus membrane-impermeant dye apoptosis staining
- ROS/oxidative-stress fluorescent staining
- BrdU Incorporation Assay
- Somatic Cell Culture
- CFSE Dye Dilution Proliferation Assay
- Dye-dilution cell tracking and proliferation staining
- CCK-8/WST-8 Cell Proliferation Assay
- Protocol for Cell Cycle
- Research Protocol for Inflammation-related Diseases
- Cell Counting-Based Growth Curve Assay
- Colony Formation (Clonogenic) Assay
- Cell Viability Determination by MTT Colorimetric Assay
- EdU Incorporation Assay (Click Chemistry-Based DNA Synthesis Measurement)
- Detection of Apoptosis
- TUNEL staining for apoptotic DNA fragmentation
- Ki-67 Immunostaining Proliferation Assay
- PCNA Immunodetection Proliferation Assay
- Protocol for Cell Counting and Cell Density Analysis
- Apoptosis Solutions
- Lysosome and acidic-vesicle live-cell staining
- MTT Cell Proliferation Assay
Chemical Information
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No. CAS 1382469-39-7
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Appearance Solid
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Peso molecular 353.48
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Fòrmula C19H23N5S
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Color Light yellow to yellow
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SMILES
S=C(N/N=C(C1=NC=CC=C1)\C2=NC=CC=C2)N(C3CCCCC3)C
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Powder -20°C 3 years In solvent -80°C 6 months -20°C 1 month
Solvente y solubilidad
In Vitro:
DMSO : 62.5 mg/mL (176.81 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
In Vivo:
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.08 mg/mL (5.88 mM); Clear solution
This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.08 mg/mL (5.88 mM); Clear solution
This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Pureza y Documentación
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Ficha de datos (302 KB)
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SDS (480 KB)
- English - EN (480 KB)
- Français - FR (480 KB)
- Deutsch - DE (480 KB)
- Norwegian - NO (480 KB)
- Español - ES (480 KB)
- Swedish - SV (480 KB)
- Italian - IT (480 KB)
- Korean - KR (480 KB)
- Portuguese - PT (480 KB)
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Instrucciones de manejo (2659 KB)
Referencias
[1]. Dharmasivam M, et al. The thiosemicarbazone, DpC, broadly synergizes with multiple anti-cancer therapeutics and demonstrates temperature- and energy-dependent uptake by tumor cells. Biochim Biophys Acta Gen Subj. 2022;1866(8):130152. [Content Brief]
[2]. Guo ZL, et al. The novel thiosemicarbazone, di-2-pyridylketone 4-cyclohexyl-4-methyl-3-thiosemicarbazone (DpC), inhibits neuroblastoma growth in vitro and in vivo via multiple mechanisms. J Hematol Oncol. 2016 Sep 27;9(1):98. [Content Brief]
[4]. Liu W, et al. The proto-oncogene c-Src and its downstream signaling pathways are inhibited by the metastasis suppressor, NDRG1. Oncotarget. 2015;6(11):8851-8874. [Content Brief]
[5]. Kovacevic Z, et al. The Metastasis Suppressor, N-MYC Downstream-regulated Gene-1 (NDRG1), Down-regulates the ErbB Family of Receptors to Inhibit Downstream Oncogenic Signaling Pathways. J Biol Chem. 2016 Jan 15;291(3):1029-52. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.8290 mL | 14.1451 mL | 28.2901 mL | 70.7254 mL |
| 5 mM | 0.5658 mL | 2.8290 mL | 5.6580 mL | 14.1451 mL | |
| 10 mM | 0.2829 mL | 1.4145 mL | 2.8290 mL | 7.0725 mL | |
| 15 mM | 0.1886 mL | 0.9430 mL | 1.8860 mL | 4.7150 mL | |
| 20 mM | 0.1415 mL | 0.7073 mL | 1.4145 mL | 3.5363 mL | |
| 25 mM | 0.1132 mL | 0.5658 mL | 1.1316 mL | 2.8290 mL | |
| 30 mM | 0.0943 mL | 0.4715 mL | 0.9430 mL | 2.3575 mL | |
| 40 mM | 0.0707 mL | 0.3536 mL | 0.7073 mL | 1.7681 mL | |
| 50 mM | 0.0566 mL | 0.2829 mL | 0.5658 mL | 1.4145 mL | |
| 60 mM | 0.0472 mL | 0.2358 mL | 0.4715 mL | 1.1788 mL | |
| 80 mM | 0.0354 mL | 0.1768 mL | 0.3536 mL | 0.8841 mL | |
| 100 mM | 0.0283 mL | 0.1415 mL | 0.2829 mL | 0.7073 mL |
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