Pyrrolidinedithiocarbamate ammonium (PDTC)

Biological Activity

Pyrrolidinedithiocarbamate ammonium (PDTC) can enhance the cell apoptosis induced by TNF-α, which may be associated with the blocking of TNF-α-activated NF-κB signaling pathway by PDTC, the down-regulation of survivin expression, and up-regulation of caspase-3 expression.in NMSC PDTC acts as pro-oxidant and enhances IR-induced cell cytotoxicity by increasing H(2)O(2)formation and thiol oxidation.PDTC and MG132, inhibitors of NF-kappaB, block ET-induced vasodilation in isolated rat skeletal muscle arterioles.PDTC has effects at both the level of the aortic segment as well as the resistance arteriole.PDTC prevents induction of nitric oxide synthase (NOS) by inhibiting translation of NOS mRNA.PDTC induces apoptosis in rat smooth muscle cells and inhibits apoptosis in leukemia HL-60 cells.

Product Citations

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  Free Radic Biol Med. 2023 Mar 27;202:46-61.

  Mitochondrial GRIM-19 loss in parietal cells promotes spasmolytic polypeptide-expressing metaplasia through NLR family pyrin domain-containing 3 (NLRP3)-mediated IL-33 activation via a reactive oxygen species (ROS) -NRF2- Heme oxygenase-1(HO-1)–NF–кB axis
  Pyrrolidinedithiocarbamate ammonium (PDTC) purchased from AbMole

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  J Extracell Vesicles. 2022 May;11(5):e12218.

  CD73 in small extracellular vesicles derived from HNSCC defines tumour‐associated immunosuppression mediated by macrophages in the microenvironment
  Pyrrolidinedithiocarbamate ammonium (PDTC) purchased from AbMole

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  Bioengineered. 2022 May;13(5):13689-13702.

  Toll-like receptor 9 (TLR9) gene deletion-mediated fracture healing in type II diabetic osteoporosis associates with inhibition of the nuclear factor-kappa B (NF-κB)
  Pyrrolidinedithiocarbamate ammonium (PDTC) purchased from AbMole

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  Int J Chron Obstruct Pulmon Dis. 2021 Jun 4;16:1661-1675.

  Histone Deacetylase 2 Suppresses Skeletal Muscle Atrophy and Senescence via NF-κB Signaling Pathway in Cigarette Smoke-Induced Mice with Emphysema
  Pyrrolidinedithiocarbamate ammonium (PDTC) purchased from AbMole

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  J Exp Clin Cancer Res. 2020 May 24;39(1):93.

  TFEB-NF-κB Inflammatory Signaling Axis: A Novel Therapeutic Pathway of Dihydrotanshinone I in Doxorubicin-Induced Cardiotoxicity
  Pyrrolidinedithiocarbamate ammonium (PDTC) purchased from AbMole

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  Oncol Rep. 2020 Aug;44(2):577-588.

  TNF‑α promotes the malignant transformation of intestinal stem cells through the NF‑κB and Wnt/β‑catenin signaling pathways
  Pyrrolidinedithiocarbamate ammonium (PDTC) purchased from AbMole

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  Cell Mol Neurobiol. 2019 Mar;39(2):301-319.

  Myosin IIA Regulated Tight Junction in Oxygen Glucose-Deprived Brain Endothelial Cells Via Activation of TLR4/PI3K/Akt/JNK1/2/14-3-3ε/NF-κB/MMP9 Signal Transduction Pathway.
  Pyrrolidinedithiocarbamate ammonium (PDTC) purchased from AbMole

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  J Infect Dis. 2018 May 8.

  Tumor Necrosis Factor-α Is Required for Mast Cell-Mediated Host Immunity Against Cutaneous Staphylococcus aureus Infection.
  Pyrrolidinedithiocarbamate ammonium (PDTC) purchased from AbMole

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  Arthritis Research & Therapy. 2018 Oct 4;20:225.

  E2F2 directly regulates the STAT1 and PI3K/AKT/NF-κB pathways to exacerbate the inflammatory phenotype in rheumatoid arthritis synovial fibroblasts and mouse embryonic fibroblasts.
  Pyrrolidinedithiocarbamate ammonium (PDTC) purchased from AbMole

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  Vet Microbiol. 2018 Sep;223:9-20.

  Dendritic cell-targeted recombinantLactobacilli induce DC activation and elicit specific immune responses against G57 genotype of avian H9N2 influenza virus infection.
  Pyrrolidinedithiocarbamate ammonium (PDTC) purchased from AbMole

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  Sci Rep. 2017 Dec 15;7(1):17677.

  Host species adaptation of TLR5 signalling and flagellin recognition
  Pyrrolidinedithiocarbamate ammonium (PDTC) purchased from AbMole

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  Vet Microbiol. 2017 May;203:158-166.

  Newcastle disease virus-like particles induce DC maturation through TLR4/NF-κB pathway and facilitate DC migration by CCR7-CCL19/CCL21 axis.
  Pyrrolidinedithiocarbamate ammonium (PDTC) purchased from AbMole

Customer Product Validations & Biological Datas

	Source	Arthritis Research & Therapy (2018). Figure 5. PDTC (Abmole Bioscience)
	Method	qRT-PCR
	Cell Lines	Synovial tissues
	Concentrations
	Incubation Time	24h
	Results	qRT-PCR showed that expression of IL-1α (Fig. 5r, u), IL-1β (Fig. 5s, v), and TNF-α (Fig. 5t, w) in response to LPS was significantly attenuated by PDTC and LY294002.

	Source	Veterinary Microbiology (2018). Figure 6. PDTC (Abmole Bioscience, Houston, TX, USA)
	Method	Detection of DC activation
	Cell Lines	DCs
	Concentrations	20 μM
	Incubation Time	2 h
	Results	The results indicated that Lp-HA-DCpep is more efficient in being englobed by DCs than Lp-HA and Lp determined by the FITC-Dextran uptake experiment (Fig. 6A) and thereby more effective in activating T cells as showed by MLR.

	Source	J Infect Dis (2018). Figure 7. PDTC (Abmole Bioscience)
	Method	Western blotting
	Cell Lines	mast cells
	Concentrations	25 μM
	Incubation Time	30 minutes
	Results	The S. aureus-induced production of TNF-α and CRAMP was significantly reduced by pretreatment with the specific PI3K inhibitor Wortmannin or the specific NF-κB inhibitor PDTC

	Source	Sci Rep (2017). Figure 4. PDTC (AbMole BioScience Inc., Brussels, Belgium)
	Method	Inhibitors of innate signalling pathways
	Cell Lines	HEK cells
	Concentrations	100 μM
	Incubation Time	24 h
	Results	As expected, RELA knock-down and the presence of PDTC, an inhibitor of NFκB, resulted in substantial reduction of CXCL8 production in response to H7 flagellin by hTLR5 in the HEK background (p < 0.05)

	Source	Vete Mic (2017). Figure 4. PDTC (Abmole Bioscience, Houston, TX, USA)
	Method	Treatment by inhibitors
	Cell Lines	DCs
	Concentrations	20 µM
	Incubation Time	48 h
	Results	The PDTC (NF-kB inhibitor) treatment significantly decreased the MHC II, CD80, CD86, CD40 expressions. As to cytokine production (Fig. 4e–h), both inhibitors significantly restrained TNF-a, IFN-g and IL-6 secretions, with a minimal effect on IL-12p70.

Chemical Information

Molecular Weight	164.29
Formula	C5H9NS2·NH3
CAS Number	5108-96-3
Solubility (25°C)	Water 30 mg/mL DMSO 30 mg/mL
Storage	Powder          -20°C   3 years ;  4°C   2 years In solvent       -80°C   6 months ;  -20°C   1 month

Conversion of different model animals based on BSA (PMID: 27057123)

Species	Mouse	Rat	Rabbit	Guinea pig	Hamster	Dog
Weight (kg)	0.02	0.15	1.8	0.4	0.08	10
Body Surface Area (m2)	0.007	0.025	0.15	0.05	0.02	0.5
Km factor	3	6	12	8	5	20

Animal A (mg/kg) = Animal B (mg/kg) multiplied by	Animal B Km
	Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the K_m factor for a mouse and then divide by the K_m factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

References

[1] Jiabin Zhu, et al. Int J Oncol. Epoxymicheliolide, a novelguaiane-type sesquiterpene lactone, inhibits NF‑κB/COX‑2 signaling pathways by targeting leucine 281 and leucine 25 in IKKβ in renal cell carcinoma

[2] Cao MZ, et al. Zhonghua Wei Chang Wai Ke Za Zhi. [NF-κb inhibitor PDTC enhances tumor necrosis factor α-induced apoptosis of gastric cancer cell SGC-7901].

[3] Thompson JS, et al. Apoptosis. Pyrrolidine dithiocarbamate (PDTC) blocks apoptosis and promotes ionizing radiation-induced necrosis of freshly-isolated normal mouse spleen cells.

[4] Snyder JG, et al. Shock. PDTC and Mg132, inhibitors of NF-kappaB, block endotoxin induced vasodilation of isolated rat skeletal muscle arterioles.