Cat. No.: 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.

For research use only. We do not sell to patients.

CAS No.: 1382469-40-0
Formula: C₁₉H₂₄ClN₅S
Molecular Weight:389.95

Storage:

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

DpC hydrochloride Chemical Structure

CAS No.: 1382469-40-0

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Use of MCE Products

One-stop solution for XDC (ADC/PDC/RDC/ApDC/FDC/ISAC/VDC/SMDC)

Biological Activity
- Description
- IC₅₀ & Target
- Cellular Effect
- In Vitro
- In Vivo
Chemical Information
Purity & Documentation
References
Calculators
Help & FAQs
Classifications
Bioz

Biological Activity

Description

IC₅₀ & Target

^[2]^[5]

JNK

NF-κB

EGFR

HER2

HER3

All JNK Isoforms :

All NF-κB Isoforms :

All Src Isoforms :

All EGFR Isoforms :

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 No. 1382469-40-0
Molecular Weight 389.95
Formula C₁₉H₂₄ClN₅S
SMILES

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

Room temperature in continental US; may vary elsewhere.
Storage

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

Purity & Documentation

Handling Instructions (2659 KB)

References

[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

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Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

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DpC hydrochloride

All JNK Isoforms

All NF-κB Isoforms

All Src Isoforms

All EGFR Isoforms