DpC hydrochloride
DpC hydrochloride is an orally active iron chelator and anticancer agent. DpC hydrochloride 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 hydrochloride selectively inhibits tumor cell proliferation and can be used in research on neuroblastoma, kidney disease, prostate cancer, and pancreatic cancer.
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- CAS No.: 1382469-40-0
- Formule: C19H24ClN5S
- Masse moléculaire:389.95
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Activité biologique
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Chemical Information
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- Pureté et documentation
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Activité biologique
Description
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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 |
|---|---|---|---|---|
| A549 | IC50 |
0.004 μM
Compound: DpC.HCI
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Antiproliferative activity at human A549 cells after 72 hrs by MTT assay
Antiproliferative activity at human A549 cells after 72 hrs by MTT assay
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[PMID: 22861499] |
| DMS-53 | IC50 |
0.007 μM
Compound: DpC.HCI
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Antiproliferative activity at human DMS53 cells after 72 hrs by MTT assay
Antiproliferative activity at human DMS53 cells after 72 hrs by MTT assay
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[PMID: 22861499] |
| MRC5 | IC50 |
10 μM
Compound: DpC.HCI
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Antiproliferative activity at human MRC5 cells after 72 hrs by MTT assay
Antiproliferative activity at human MRC5 cells after 72 hrs by MTT assay
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[PMID: 22861499] |
In Vitro
DpC (0.125-8 × IC50; 72 h) hydrochloride 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 hydrochloride 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) hydrochloride 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) hydrochloride 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) hydrochloride 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) hydrochloride induces NDRG1 and inhibits c-Src activation at Tyr416 in DU145 cells without altering total c-Src[4].
DpC (10 µM) hydrochloride upregulates NDRG1 and reduces EGFR protein levels and membrane localization in PANC-1 and HT-29 cells[5].
DpC (10 µM; 24 h) hydrochloride 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) hydrochloride 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) hydrochloride 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) hydrochloride increases NDRG1 and decreases EGFR/pEGFR (Tyr-1068) in PANC-1 and HT-29 cells; the DpC hydrochloride-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) hydrochloride 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) hydrochloride 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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CAS No. 1382469-40-0
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Masse moléculaire 389.95
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Formule C19H24ClN5S
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SMILES
S=C(N(C1CCCCC1)C)N/N=C(C2=NC=CC=C2)\C3=NC=CC=C3.Cl
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureté et documentation
Références
[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]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
DpC hydrochloride Related Classifications
HY-114243A Related Classifications
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