WK-X-34
WK-X-34 is a low-toxicity, highly effective multidrug resistance reversal agent. By potently inhibiting the transport functions of P-glycoprotein (P-gp, ABCB1) and breast cancer resistance protein (BCRP), WK-X-34 significantly increases the intracellular accumulation of anticancer drugs and radiotracers in drug-resistant cells. WK-X-34 exerts no significant effect on MRP transporters. WK-X-34 not only restores the chemosensitivity of multidrug-resistant ovarian cancer cells, but also significantly enhances the uptake of 99mTc-Sestamibi in P-gp-positive xenograft tumors, brain and intestinal tissues. WK-X-34 exhibits extremely low toxicity and favorable safety profiles both in vitro and in mice (at doses up to 50 mg/kg), and can be used for research on overcoming multidrug resistance in ovarian cancer.
For research use only. We do not sell to patients.
- CAS No.: 908859-10-9
- Formula: C35H37N3O6
- Molecular Weight:595.70
-
Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
-
Biological Activity
-
Chemical Information
- Purity & Documentation
- References
-
Help & FAQs
Biological Activity
|
Cell Line
|
Type | Value | Description | References |
|---|---|---|---|---|
| DU-145 | IC50 |
8.7 nM
Compound: WK-X-34
|
Reversal of docetaxel resistance in human DU-145 cells transfected with CYP1B1 assessed as decrease in docetaxel IC50 at 5 uM (Rvb = 23.5 +/- 3.04 nM)
Reversal of docetaxel resistance in human DU-145 cells transfected with CYP1B1 assessed as decrease in docetaxel IC50 at 5 uM (Rvb = 23.5 +/- 3.04 nM)
|
[PMID: 39418747] |
| K562 | IC50 |
19.56 μM
Compound: WK-X-34
|
Cytotoxicity against human K562 cells assessed as cell viability after 48 hrs by MTT assay
Cytotoxicity against human K562 cells assessed as cell viability after 48 hrs by MTT assay
|
[PMID: 27073052] |
| K562/A02 | EC50 |
30.3 nM
Compound: W34; WK-X-34
|
Reversal of adriamycin resistance in human K562/A02 cells incubated for 48 hrs
Reversal of adriamycin resistance in human K562/A02 cells incubated for 48 hrs
|
[PMID: 36708676] |
| K562/A02 | IC50 |
0.029 μM
Compound: W34; WK-X-34
|
Reversal of multi-drug resistance in human K562/A02 cells assessed as ADR IC50
Reversal of multi-drug resistance in human K562/A02 cells assessed as ADR IC50
|
[PMID: 36708676] |
| K562/A02 | IC50 |
50.1 μM
Compound: WK-X-34
|
Cytotoxicity against human K562/A02 cells assessed as cell viability after 48 hrs by MTT assay
Cytotoxicity against human K562/A02 cells assessed as cell viability after 48 hrs by MTT assay
|
[PMID: 27073052] |
| K562/A02 | IC50 |
9.08 μM
Compound: W34; WK-X-34
|
Cytotoxicity against human K562/A02 cells assessed as inhibition of cell growth incubated for 72 hrs by CCK-8 assay
Cytotoxicity against human K562/A02 cells assessed as inhibition of cell growth incubated for 72 hrs by CCK-8 assay
|
[PMID: 36708676] |
| MCF7 | IC50 |
0.93 μM
Compound: 4a
|
Inhibition of BCRP expressed in MCF7 MX cells by Hoechst 33342 staining
Inhibition of BCRP expressed in MCF7 MX cells by Hoechst 33342 staining
|
[PMID: 19932960] |
| MDCK | IC50 |
0.86 μM
Compound: 4a
|
Inhibition of BCRP expressed in MDCK cells by pheophorbide A assay
Inhibition of BCRP expressed in MDCK cells by pheophorbide A assay
|
[PMID: 19932960] |
| SW-620 | IC50 |
0.063 μM
Compound: WK-X-34
|
Reversal of doxorubicin-induced multidrug resistance in human SW620 cells measured after 48 hrs by CCK-8 method
Reversal of doxorubicin-induced multidrug resistance in human SW620 cells measured after 48 hrs by CCK-8 method
|
[PMID: 38389882] |
| SW620/AD300 | IC50 |
0.223 μM
Compound: WK-X-34
|
Reversal of doxorubicin-induced multidrug resistance in human SW620/AD300 cells measured after 48 hrs by CCK-8 method
Reversal of doxorubicin-induced multidrug resistance in human SW620/AD300 cells measured after 48 hrs by CCK-8 method
|
[PMID: 38389882] |
WK-X-34 (10 nM-100 μM; 15 min pre-incubation, 180 min total with daunorubicin) potently inhibits Pgp-mediated efflux in A2780/Adr cells with an IC50 of 82.1 ± 6 nM, and the inhibitory effect persists for 24 hours after removal of the compound[1].
WK-X-34 (10 μM; 1 hr pre-incubation, 0-60 min 99ᵐTc-Sestamibi incubation) completely inhibits Pgp-mediated efflux of 99ᵐTc-Sestamibi in A2780/Adr cells at 10 μM, with an IC50 of 417 ± 189.7 nM, restoring tracer accumulation to levels seen in Pgp-negative A2780/wt cells[1].
WK-X-34 (1-1000 μM; 90 min after mitoxantrone preloading) inhibits BCRP-mediated mitoxantrone efflux in MCF7/mx cells with an IC50 of 26.5 ± 4.6 μM, without altering mitoxantrone handling in BCRP-negative MCF7 cells[1].
WK-X-34 (10 nM-10 mM; 72 hr) has low in vitro cytotoxicity in A2780/Adr and A2780/wt cells, with LD50 values well above its Pgp inhibitory IC50 concentrations[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Cell Line:P-gp-overexpressing human ovarian cancer A2780/Adr cells,
P-gp-negative human ovarian cancer A2780/wt cells -
Concentration:10 nM, 100 nM, 1 μM, 10 μM, 100 μM, 1 mM, 10 mM
-
Incubation Time:72 hr
-
Result:Showed low cytotoxicity in both cell lines, with LD50 values of 152 ± 281 μM in A2780/Adr cells and 112 ± 112 μM in A2780/wt cells.
WK-X-34 (20-50 mg/kg; i.p.; daily; 14 days) is well tolerated in healthy male CD-1 mice, with no observable toxicity or hepatotoxicity[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Animal Model:BalbC nu/nu (5-week-old female, 20-25 g, subcutaneous implantation of human ovarian cancer cells)[1]
-
Dosage:20 mg/kg
-
Administration:i.p.; single dose
-
Result:Increased 99mTc-Sestamibi AUC0-4h by 136% in A2780/Adr xenograft tumors, with no significant change in A2780/wt tumors.
Increased 99mTc-Sestamidium accumulation 9-fold in A2780/Adr tumors (0.95% ID/g tissue vs control 0.09% ID/g tissue).
Increased A2780/Adr tumor-to-muscle ratio from 0.05 to 0.45.
Increased 99mTc-Sestamidium AUC0-4h by 147% in brain and 138% in intestine.
Increased 99mTc-Sestamidium accumulation in heart (10.09% ID/g tissue vs control 5.90% ID/g tissue), liver (11.91% ID/g tissue vs control 5.83% ID/g tissue), muscle (2.58% ID/g tissue vs control 1.63% ID/g tissue), and brain (0.10% ID/g tissue vs control 0.06% ID/g tissue).
Chemical Information
-
CAS No. 908859-10-9
-
Molecular Weight 595.70
-
Formula C35H37N3O6
-
SMILES
O=C(NC=1C=CC=CC1C(=O)NC2=CC=C(C=C2)CCN3CC4=CC(OC)=C(OC)C=C4CC3)C5=CC=C(OC)C(OC)=C5
-
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
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Powered by Bioz