PAO-PDT
PAO-PDT is an organoarsenic inhibitor of thioredoxin reductase (TrxR), with an IC50 of 33 nM. PAO-PDT can bind to the C-terminal selenocysteine/cysteine pair of TrxR and convert the enzyme into an NADPH oxidase, which increases reactive oxygen species levels and impairs mitochondrial respiratory function, thereby inducing apoptosis in leukemia cells. PAO-PDT can be used for leukemia research.
For research use only. We do not sell to patients.
- CAS No.: 256348-71-7
- Formula: C9H12AsNS2
- Molecular Weight:273.24
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
- Protocols
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Description
IC50 & Target
[2]|
TrxR 33 nM (IC50) |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| HL-60 | IC50 |
0.7 μM
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Cytotoxicity against human promyelocytic leukemia HL-60 cells assessed as inhibition of proliferation incubated for 48 hrs by MTT assay.
Cytotoxicity against human promyelocytic leukemia HL-60 cells assessed as inhibition of proliferation incubated for 48 hrs by MTT assay.
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41338133 |
| HL-60 | IC50 |
0.6 μM
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Cytotoxicity against human promyelocytic leukemia HL-60 cells assessed as inhibition of proliferation incubated for 72 hrs by MTT assay.
Cytotoxicity against human promyelocytic leukemia HL-60 cells assessed as inhibition of proliferation incubated for 72 hrs by MTT assay.
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41338133 |
| SMMC-7721 | IC50 |
2.8 μM
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Cytotoxicity against human hepatocellular carcinoma 7721 cells assessed as inhibition of proliferation incubated for 48 hrs by MTT assay.
Cytotoxicity against human hepatocellular carcinoma 7721 cells assessed as inhibition of proliferation incubated for 48 hrs by MTT assay.
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41338133 |
| HeLa | IC50 |
3.4 μM
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Cytotoxicity against human cervical cancer HeLa cells assessed as inhibition of proliferation incubated for 48 hrs by MTT assay.
Cytotoxicity against human cervical cancer HeLa cells assessed as inhibition of proliferation incubated for 48 hrs by MTT assay.
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41338133 |
| HepG2 | IC50 |
> 10 μM
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Cytotoxicity against human hepatocellular carcinoma HepG2 cells assessed as inhibition of proliferation incubated for 48 hrs by MTT assay.
Cytotoxicity against human hepatocellular carcinoma HepG2 cells assessed as inhibition of proliferation incubated for 48 hrs by MTT assay.
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41338133 |
| L02 | IC50 |
10.2 μM
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Cytotoxicity against human normal liver L02 cells assessed as inhibition of proliferation by MTT assay.
Cytotoxicity against human normal liver L02 cells assessed as inhibition of proliferation by MTT assay.
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41338133 |
| HEK-293T | IC50 |
2.7 μM
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Cytotoxicity against human embryonic kidney HEK 293T cells assessed as inhibition of proliferation by MTT assay.
Cytotoxicity against human embryonic kidney HEK 293T cells assessed as inhibition of proliferation by MTT assay.
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41338133 |
| HL-60 | IC50 |
1.4 μM
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Inhibition of cellular thioredoxin reductase activity in human promyelocytic leukemia HL-60 cells.
Inhibition of cellular thioredoxin reductase activity in human promyelocytic leukemia HL-60 cells.
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41338133 |
| HL-60 | IC50 |
0.81 μM
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Cytotoxicity against human HL-60 malignant cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay.
Cytotoxicity against human HL-60 malignant cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay.
|
30665675 |
| HeLa | IC50 |
4.86 μM
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Cytotoxicity against human HeLa malignant cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay.
Cytotoxicity against human HeLa malignant cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay.
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30665675 |
| SMMC-7721 | IC50 |
5.24 μM
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Cytotoxicity against human SMMC-7721 malignant cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay.
Cytotoxicity against human SMMC-7721 malignant cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay.
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30665675 |
| HepG2 | IC50 |
2.27 μM
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Cytotoxicity against human HepG2 malignant cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay.
Cytotoxicity against human HepG2 malignant cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay.
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30665675 |
In Vitro
PAO-PDT (compound 4) selectively and potently inhibits the proliferation of human promyelocytic leukemia HL-60 cells within 48-72 h, with IC50 values of 0.7 μM (48 h) and 0.6 μM (72 h), respectively, while exhibiting low cytotoxicity against other cancer cell lines and normal cells[1].
PAO-PDT (2.0-5.0 μM; 48 h) exhibits weak effects on human embryonic kidney HEK-TrxR1 cells with overexpressed TrxR, whereas human cervical carcinoma HeLa-shTrxR1 cells with TrxR knockdown are more sensitive to PAO-PDT, which confirms that TrxR targeting mediates the cytotoxicity of PAO-PDT[1].
PAO-PDT (48 h) inhibits the proliferation of HL-60 cells, with an IC50 of 0.70 μM after 48 h of incubation[2].
PAO-PDT (compound 8) (48 h) potently inhibits the viability of HL-60 leukemia cells with an IC50 of 0.81 μM, and exhibits low cytotoxicity against HeLa, SMMC-7721, and HepG2 cells[4].
PAO-PDT (24-48 h) inhibits the viability of NB4, HL-60, HeLa, SGC7901, MCF-7, and HEK293 cells in vitro, with the highest potency against NB4 cells (IC50 = 0.82 μM at 48 h)[3].
PAO-PDT (0.6-3.6 μM; 1-8 h) induces a time- and concentration-dependent decrease in the viability of NB4 cells in vitro, and after incubation with 3.6 μM PAO-PDT for 8 h, the cell viability decreases to approximately 0.38[3].
PAO-PDT (50-200 nM) potently inhibits the purified wild-type TrxR at concentrations of 50 nM and above, but does not inhibit the purified U498C mutant TrxR at the same concentrations[1].
PAO-PDT inhibits recombinant rat wild-type thioredoxin reductase with an IC50 of approximately 33 nM, and exhibits no significant inhibitory effect on U498C TrxR, GR, GPx, or Trx[1].
PAO-PDT (1-2 μM; 12-24 h) inhibits the activity of cellular thioredoxin reductase in human promyelocytic leukemia HL-60 cells, with an IC50 of approximately 1.4 μM; it also directly binds to endogenous TrxR1 and upregulates the expression of TrxR1 protein at concentrations of 1 μM (24 h) and 2 μM (12 h)[1].
PAO-PDT (1-10 μM; 12-24 h) induces concentration-dependent cellular thiol depletion in human promyelocytic leukemia HL-60 cells, and the degree of depletion after 24 h is greater than that after 12 h[1].
PAO-PDT potently inhibits purified TrxR with an IC50 of 33 nM[2].
PAO-PDT (30 min) inhibits the activity of purified recombinant rat TrxR1 and exhibits extremely low inhibitory activity against GR[4].
PAO-PDT (2 μM; 24 h) inhibits cellular TrxR activity in HL-60 cells by approximately 40%[4].
PAO-PDT (1 μM; 1-2 h) induces time-dependent reactive oxygen species accumulation in human promyelocytic leukemia HL-60 cells[1].
PAO-PDT (1.2 μM; 1-6 h) induces mild short-term ROS accumulation in NB4 cells in vitro[3].
PDT-PAO (15-100 μM) regulates mitochondrial respiration in isolated rat liver mitochondria[3].
PDT-PAO (0.3-2.4 μM; 24 h) increases the intracellular ROS level in NB4 cells in a concentration-dependent manner in vitro, and the induction effect reaches its peak at 2.4 μM[3].
The cytotoxicity of PAO-PDT (0.01-2.0 μM; 48 h) against human promyelocytic leukemia HL-60 cells is inhibited by Acetylcysteine (HY-B0215) in a dose-dependent manner, while pretreatment with L-Buthionine-(S,R)-sulfoximine (HY-106376A) enhances the cytotoxicity of PAO-PDT[1].
PAO-PDT (0.5-5 μM; 12-24 h) induces dose- and time-dependent apoptotic cell death in human promyelocytic leukemia HL-60 cells, and the proportion of apoptotic cells observed at 24 h is higher than that at 12 h[1].
PAO-PDT (0.5-2 μM; 24 h) induces concentration-dependent activation of caspase-3 in human promyelocytic leukemia HL-60 cells after 24 h of treatment[1].
PAO-PDT (0.5-5 μM; 24 h) induces apoptotic nuclear morphology in human promyelocytic leukemia HL-60 cells after 24 h of treatment, characterized by nuclear pyknosis and high fluorescence intensity[1].
PDT-PAO (0.6-2.4 μM; 4-24 h) reduces the total thiol level in NB4 cells in a concentration- and time-dependent manner, with the most potent reduction observed after treatment with 2.4 μM for 24 h[3].
PDT-PAO (1.2-2.4 μM; 24 h) increases the level of cytochrome c in NB4 cells[3].
PAO-PDT (1.2 μM; 1-6 h) induces a slight time-dependent collapse of mitochondrial membrane potential in NB4 cells in vitro[3].
PAO-PDT (1.2-2.4 μM; 24 h) reduces the intracellular ATP level in NB4 cells in a concentration-dependent manner in vitro. After incubation with 2.4 μM PAO-PDT for 24 h, the ATP level decreases to ~5 μmol/g protein[3].
PAO-PDT (50-200 μM) inhibits thermogenesis in isolated mitochondria from NB4 cells in vitro. At 100 μM, it reduces the maximum power output to 96.9 μW and slows the rate constants of the activity recovery phase, steady-state rise phase, and decline phase[3].
PDT-PAO (1-5 μM; 2.5-5 h) inhibits PDHC activity in NB4 cells, and the enzyme activity in the treatment groups at concentrations of 1 μM and 5 μM (incubated for 2.5 h) as well as 2.4 μM (incubated for 5 h) decreases compared with the untreated control group[3].
PDT-PAO (2.4 μM; 24 h) reduces the viability of NB4 cells, and this effect is reversed in a concentration-dependent manner upon combined treatment with LA[3].
PDT-PAO (1.5-2 μM; 24 h) reduces the viability of NB4 cells, and this effect is observed at both concentrations of 1.5 μM and 2 μM (with 24 h incubation); however, this effect is reversed in a concentration-dependent manner upon combined treatment with DL-Dithiothreitol (DTT) (HY-15917), Dimethyl phthalate (DMP) (HY-N7106), or Succimer (DMSA) (HY-B1768)[3].
PDT-PAO (0.6-3.6 μM; 12-24 h) reduces the viability of NB4 cells in a concentration- and time-dependent manner, with incubation durations of 12 h or 24 h; pretreatment with 50 μM DL-Buthionine-(S,R)-sulfoximine (BSO) (HY-106376) enhances this cytotoxic effect[3].
The combination of PDT-PAO (25-150 μM) with 4 μM Ca2+ induces swelling of isolated rat liver mitochondria in a concentration-dependent manner[3].
PDT-PAO (50-200 μM) induces negligible H+ permeability of the mitochondrial inner membrane in isolated rat liver mitochondria, and only causes slight alterations in K+ permeability [3].
Incubation with PDT-PAO (100 μM; 30 min) for 30 min induces ultrastructural damage in isolated rat liver mitochondria[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:human promyelocytic leukemia HL-60 cells, human hepatocellular carcinoma 7721 cells, human cervical cancer HeLa cells, human hepatocellular carcinoma HepG2 cells, human normal liver L02 cells, human embryonic kidney HEK 293T cells
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Concentration:0.7 μM (HL-60 cells, 48 h); 0.6 μM (HL-60 cells, 72 h); 2.8 μM (7721 cells, 48 h); 3.4 μM (HeLa cells, 48 h); 10.2 μM (L02 cells); 2.7 μM (HEK 293T cells)
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Incubation Time:48 h (HL-60, 7721, HeLa cells); 72 h (HL-60 cells); null (L02, HEK 293T cells)
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Result:Exhibited selective, potent cytotoxicity toward HL-60 cells, with IC50 values of 0.7 μM (48 h) and 0.6 μM (72 h).
Showed lower cytotoxicity toward 7721 cells (IC50 = 2.8 μM, 48 h) and HeLa cells (IC50 = 3.4 μM, 48 h), with no cytotoxicity toward HepG2 cells (IC50 > 10 μM, 48 h).
Displayed reduced toxicity toward normal cells, with IC50 values of 10.2 μM (L02) and 2.7 μM (HEK 293T).
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Cell Line:human promyelocytic leukemia HL-60 cells
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Concentration:0, 0.5, 1.0, 2.0 μM (with 0, 0.1, 1.0, 2.0 mM NAC); 0, 0.01, 0.1, 1 μM (with 100 μM BSO pre-treatment)
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Incubation Time:48 h (NAC co-treatment); 24 h (BSO pre-treatment) followed by 48 h incubation
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Result:NAC dose-dependently protected HL-60 cells from PAO-PDT-induced cytotoxicity.
BSO pre-treatment enhanced PAO-PDT cytotoxicity in HL-60 cells.
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Cell Line:human embryonic kidney HEK-IRES (vector control) cells, human embryonic kidney HEK-TrxR1 (TrxR-overexpressing) cells, human cervical cancer HeLa-shNT (nontargeting shRNA control) cells, human cervical cancer HeLa-shTrxR1 (TrxR-knockdown) cells
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Concentration:2.0, 5.0 μM
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Incubation Time:48 h
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Result:HEK-TrxR1 cells (overexpressing TrxR) showed significantly higher viability than HEK-IRES control cells after PAO-PDT treatment.
HeLa-shTrxR1 cells (TrxR-knockdown) showed lower viability than HeLa-shNT control cells after PAO-PDT treatment.
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Cell Line:human promyelocytic leukemia HL-60 cells
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Concentration:0, 0.5, 2, 5 μM (12 h incubation); 0, 0.5, 2, 5 μM (24 h incubation)
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Incubation Time:12 h; 24 h
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Result:Induced dose- and time-dependent apoptotic cell death in HL-60 cells, with increased apoptotic populations (early and late apoptosis) after 24 h compared to 12 h.
Maintained necrotic cell population as low as that of the control.
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Cell Line:human promyelocytic leukemia HL-60 cells
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Concentration:0, 0.5, 2, 5 μM
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Incubation Time:24 h
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Result:Revealed characteristic condensed, highly fluorescent nuclei in PAO-PDT-treated HL-60 cells, confirming apoptotic morphology.
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Cell Line:NB4
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Concentration:0.6-3.6 μM
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Incubation Time:1 h, 4 h, 8 h
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Result:Induced time- and concentration-dependent decreases in cell viability.
Reduced viability to ~0.38 at 3.6 μM after 8 h of incubation.
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Cell Line:NB4
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Concentration:0.4-1.6 μM
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Incubation Time:12 h, 24 h
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Result:Had its induced cell viability loss enhanced by pre-incubation with 50 μM BSO (a GSH scavenger).
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Cell Line:NB4 cells
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Concentration:2.4 μM; 2.4 μM with 0.05 mM LA; 2.4 μM with 0.075 mM LA
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Incubation Time:24 h
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Result:Reduced NB4 cell viability to near 0 at 2.4 μM alone after 24 h incubation.
Increased viability to approximately 0.4 when co-incubated with 0.05 mM LA.
Increased viability to approximately 0.9 when co-incubated with 0.075 mM LA.
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Cell Line:NB4 cells
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Concentration:1.5 μM; 2 μM; 1.5 μM with 250 μM DTT; 1.5 μM with 500 μM DTT; 2 μM with 100 μM DMP; 2 μM with 300 μM DMP; 1.5 μM with 100 μM DMSA; 1.5 μM with 150 μM DMSA
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Incubation Time:24 h
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Result:Reduced NB4 cell viability to approximately 0.5 at 1.5 μM alone after 24 h incubation.
Increased viability to approximately 0.7 when co-incubated with 250 μM DTT.
Increased viability to approximately 0.8 when co-incubated with 500 μM DTT.
Reduced viability to approximately 0.15 at 2 μM alone after 24 h incubation.
Increased viability to approximately 0.6 when co-incubated with 100 μM DMP.
Increased viability to approximately 0.9 when co-incubated with 300 μM DMP.
Increased viability to approximately 0.75 when co-incubated with 100 μM DMSA.
Increased viability to approximately 0.8 when co-incubated with 150 μM DMSA.
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Cell Line:NB4 cells
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Concentration:0.6 μM, 1.2 μM, 2.4 μM, 3.6 μM; 0.6 μM with 50 μM BSO pre-treatment, 1.2 μM with 50 μM BSO pre-treatment, 2.4 μM with 50 μM BSO pre-treatment, 3.6 μM with 50 μM BSO pre-treatment
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Incubation Time:12 h, 24 h
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Result:Reduced NB4 cell viability to ~0.8 at 0.6 μM, ~0.6 at 1.2 μM, ~0.3 at 2.4 μM, and ~0.1 at 3.6 μM after 12 h incubation.
Reduced NB4 cell viability to ~0.8 at 0.6 μM, ~0.7 at 1.2 μM, ~0.4 at 2.4 μM, and ~0.2 at 3.6 μM after 24 h incubation.
Enhanced the viability-reducing effect with 50 μM BSO pre-treatment, resulting in viability of ~0.05 at 3.6 μM after 12 h incubation, and ~0.5 at 3.6 μM after 24 h incubation.
Chemical Information
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CAS No. 256348-71-7
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Molecular Weight 273.24
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Formula C9H12AsNS2
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SMILES
S1[As](SCCC1)C2=CC=C(N)C=C2
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocols
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Apoptosis
Apoptosis, also called programmed cell death, is generally characterized by distinct morphological characteristics.
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TUNEL staining for apoptotic DNA fragmentation
TUNEL staining detects DNA strand breaks by using terminal deoxynucleotidyl transferase to add labeled nucleotides to exposed 3′-OH DNA termini, generating either microscopic staining in fixed cells or tissue sections, or fluorescence/cytometric signal in cell suspensions. TUNEL positivity reflects DNA fragmentation but should not be interpreted alone as definitive apoptosis, because TUNEL can also label necrotic, autolytic, mechanically damaged, or DNA-repair-associated DNA breaks.
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Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
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Annexin V plus membrane-impermeant dye apoptosis staining
Annexin V-based apoptosis assays rely on the detection of phosphatidylserine (PS) externalization from the inner leaflet of the plasma membrane to the outer leaflet, an early biochemical hallmark of apoptosis. Fluorescently labeled Annexin V binds PS in a calcium-dependent manner, enabling identification of early apoptotic cells by flow cytometry or fluorescence microscopy. When combined with a membrane-impermeant DNA-binding dye (e. g. , propidium iodide), this approach allows discrimination between viable (Annexin V−/dye−), early apoptotic (Annexin V+/dye−), and late apoptotic or necrotic (Annexin V+/dye+) cell populations by assessing membrane integrity and PS exposure.
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ROS/oxidative-stress fluorescent staining
ROS/oxidative-stress fluorescent staining uses cell-permeant fluorogenic probes that become fluorescent after oxidation inside cells or tissues; commonly used examples include DCFH-DA/DCFDA for broad cellular oxidant detection, DHE for superoxide-related signal detection, MitoSOX for mitochondrial superoxide-related signal detection, and CellROX probes for oxidative-stress-associated fluorescence readouts. The assay detects probe oxidation rather than a single ROS species unless the probe and analysis method have been chemically validated for that species. DCFH-DA enters cells, is deacetylated by intracellular esterases to DCFH, and produces fluorescent DCF after oxidation, so the readout is used as an operational measure of total cellular oxidative stress rather than a species-specific ROS measurement. DHE and MitoSOX can report superoxide-related oxidation, but red fluorescence alone can include non-specific ethidium-like oxidation products; HPLC or optimized spectral approaches are
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Apoptosis Solutions
Apoptosis is a regulated, generally non-lytic cell-death pathway that removes unwanted, damaged, infected, or abnormal cells through coordinated morphological changes, caspase activation, DNA fragmentation, and membrane remodeling. The intrinsic apoptosis pathway is controlled mainly by mitochondrial outer membrane permeabilization, BCL-2 family proteins, cytochrome c release, apoptosome formation, caspase-9 activation, and downstream executioner caspase-3/7 activation. The extrinsic apoptosis pathway is initiated by death receptors such as Fas, TNFR, and TRAIL receptors, which recruit adaptor proteins and activate caspase-8 before engaging executioner caspases or mitochondrial amplification through BID cleavage. Apoptosis is linked to many phenotypes, including cancer cell killing, tissue homeostasis, immune regulation, neurodegeneration, infection response, and treatment-induced cytotoxicity; unresolved questions include how apoptosis interacts with necroptosis, pyroptosis, ferroptos
Purity & Documentation
References
[1]. Liu Y, et al. Dithiaarsanes induce oxidative stress-mediated apoptosis in HL-60 cells by selectively targeting thioredoxin reductase. Journal of medicinal chemistry. 2014 Jun 26;57(12):5203-11. [Content Brief]
[2]. Shi S, et al. Structure-Guided optimization of PAO-PDT yields TrxR inhibitors as potential anticancer agent. European journal of medicinal chemistry. 2026 Feb 05;303:118407. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
PAO-PDT Related Classifications
HY-116032 Related Classifications
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