Art. -Nr.: HY-114243A

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. Nr.: 1382469-40-0
Formel: C₁₉H₂₄ClN₅S
Molecular Weight:389.95

Speicherung:

Please store the product under the recommended conditions in the Certificate of Analysis.

DpC hydrochloride Chemical Structure

CAS. Nr.: 1382469-40-0

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Biologische Aktivität
- Beschreibung
- IC₅₀ & Target
- Cellular Effect
- In Vitro
- In Vivo
Chemical Information
Reinheit & Dokumentation
Verweise
Calculators
Help & FAQs
Classifications
Bioz

Biologische Aktivität

Beschreibung

IC₅₀ & Target

^[2]^[5]

JNK

NF-κB

EGFR

HER2

HER3

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Cellular Effect

Cell Line	Type	Value	Description	References
A549	IC₅₀	0.004 μM Compound: DpC.HCI	Antiproliferative activity at human A549 cells after 72 hrs by MTT assay Antiproliferative activity at human A549 cells after 72 hrs by MTT assay	[PMID: 22861499]
DMS-53	IC₅₀	0.007 μM Compound: DpC.HCI	Antiproliferative activity at human DMS53 cells after 72 hrs by MTT assay Antiproliferative activity at human DMS53 cells after 72 hrs by MTT assay	[PMID: 22861499]
MRC5	IC₅₀	10 μM Compound: DpC.HCI	Antiproliferative activity at human MRC5 cells after 72 hrs by MTT assay Antiproliferative activity at human MRC5 cells after 72 hrs by MTT assay	[PMID: 22861499]

In Vitro

Anti-cancerApoptosisOthers

Anti-cancer

DpC (serial dilution; 24-72 h) hydrochloride inhibits the proliferation of PANC-1, PC3, DMS-53, DU-145, and MDA-MB-231 cells, with IC₅₀ values at 72 h of 0.096, 0.007, 0.020, 0.007, and 0.008 μM, respectively^[1].
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].

Anti-cancer

Apoptosis

DpC (25 μM; 24 h) hydrochloride induces apoptosis in all four neuroblastoma cell lines, with SK-N-AS showing the highest proportion of early apoptosis (42.3%) and SK-N-LP showing the highest proportion of late apoptosis (27.4%)^[2].
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].

Others

DpC hydrochloride does not show obvious cytotoxicity against HK-2 human proximal tubular epithelial cells and L929 cells^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Viability Assay^[2]

Cell Line:

human neuroblastoma SK-N-LP cells and non-tumorigenic immortalized MSC, H9C2, MIHA, and HK2 cells
Concentration:

2.5, 25, and 250 μM (24 h); 25 μM (24, 48, and 72 h)
Incubation Time:

12, 24, 48, and 72 h
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.

Apoptosis Analysis^[2]

Cell Line:

human neuroblastoma cell lines SK-N-LP, BE(2)C, SK-N-AS, and SH-SY5Y
Concentration:

25 μM
Incubation Time:

24 h
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.

Western Blot Analysis^[2]

Cell Line:

human SK-N-LP neuroblastoma cells
Concentration:

25 μM
Incubation Time:

24 h
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.

Cell Viability Assay^[2]

Cell Line:

SK-N-LP neuroblastoma cells
Concentration:

25 μM
Incubation Time:

24 h (after 2 h inhibitor pre-incubation)
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.

Western Blot Analysis^[4]

Cell Line:

DU145 human prostate cancer cells
Concentration:

5 μM
Incubation Time:

24 h
Result:

Increased NDRG1 protein expression relative to untreated control.
Decreased phosphorylation of c-Src at Tyr416.
Did not alter total c-Src protein levels.

Western Blot Analysis^[5]

Cell Line:

PANC-1 and HT-29 cells
Concentration:

10 µM
Incubation Time:

24 h
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.

Western Blot Analysis^[5]

Cell Line:

PANC-1 and HT-29 cells
Concentration:

10 µM
Incubation Time:

24 h
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.

Cell Proliferation Assay^[5]

Cell Line:

PANC-1, MIAPaCa-2, HT-29, and HCT-116 cells
Concentration:

0.08, 0.31, 1.25, 5, 20, and 80 µM
Incubation Time:

72 h
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.

Western Blot Analysis^[5]

Cell Line:

PANC-1 and HT-29 cells
Concentration:

10 µM (DpC); 1 µM (DpC-copper complex)
Incubation Time:

24 h (DpC and DpC-copper complex)
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

Anti-cancerApoptosisCytokines & Chemokines

Anti-cancer

DpC (5 mg/kg; i.v. via tail vein; 5 days/week (Monday to Friday); for 23 days) hydrochloride inhibits PANC-1 xenograft tumor growth and reduces tumor EGFR, HER2, and HER3 expression in nude mice^[5].

Anti-cancer

Apoptosis

Cytokines & Chemokines

DpC (4 mg/kg/day; i.v.; daily; 3 weeks) hydrochloride reduces orthotopic neuroblastoma tumor burden and promotes tumor apoptosis in nude mice^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:

BALB/c nu/nu nude (male, 4 weeks old)^[2]
Dosage:

4 mg/kg/day
Administration:

i.v. (tail vein); daily; 3 weeks
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.

Animal Model:

BALB/c nu/nu nude (female, 8 weeks old)^[5]
Dosage:

5 mg/kg (as DpC HCl)
Administration:

i.v. via tail vein; 5 days/week (Monday to Friday); for 23 days
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.

Related Protocols :

Chemical Information

CAS. Nr. 1382469-40-0
Molecular Weight 389.95
Formel C₁₉H₂₄ClN₅S
SMILES

S=C(N(C1CCCCC1)C)N/N=C(C2=NC=CC=C2)\C3=NC=CC=C3.Cl
Versand

Room temperature in continental US; may vary elsewhere.
Speicherung

Please store the product under the recommended conditions in the Certificate of Analysis.

Reinheit & Dokumentation

Handling Instructions (2659 KB)

Verweise

[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]

[3]. Lin Y, et al. Synthesis and in vivo distribution of 2-deoxy-2-aminodiglucose–prednisolone conjugate (DPC). Chinese Chemical Letters, 2012, 23(5): 557-560.

[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]

[6]. Jiaming Liu, et al.Generation of reactive oxygen species through dissolved oxygen activation on defected porous carbon for efficient degradation of antibiotics, Chemical Engineering Journal, Volume 455, 2023, 140602, ISSN 1385-8947.

Calculators

Molaritätsrechner

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass Mass

Konzentration Konzentration

Volumen Volumen

Molecular Weight Molecular Weight

Verdünnungsrechner

Konzentration _{(Stammlösung)} × Volumen _{(Stammlösung)} = Konzentration _{(Ziellösung)} × Volumen _{(Ziellösung)}

Konzentration _{(Stammlösung)} Konzentration _{(Stammlösung)}

Volumen _{(Stammlösung)} Volumen _{(Stammlösung)}

Konzentration _{(Ziellösung)} Konzentration _{(Ziellösung)}

Volumen _{(Ziellösung)} Volumen _{(Ziellösung)}

Help & FAQs

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DpC hydrochloride

Alle JNK Isoform-spezifische Produkte anzeigen

Alle NF-κB Isoform-spezifische Produkte anzeigen

Alle Src Isoform-spezifische Produkte anzeigen

Alle EGFR Isoform-spezifische Produkte anzeigen