PROTAC AKR1C3 degrader-1
PROTAC AKR1C3 degrader-1 is a PROTAC degrader targeting AKR1C3, with a DC50 of 52 nM. PROTAC AKR1C3 degrader-1 induces proteasome-dependent degradation of AKR1C3 and inhibits the enzymatic activities of AKR1C3, AKR1C1 and AKR1C2. PROTAC AKR1C3 degrader-1 degrades ARv7 by disrupting the stable AKR1C3/ARv7 complex. PROTAC AKR1C3 degrader-1 reduces the viability of prostate cancer cells expressing AKR1C3 and sensitizes Enzalutamide (HY-70002)-resistant prostate cancer cells. PROTAC AKR1C3 degrader-1 can be used in the research of prostate cancer.
(Pink: Aldose Reductase ligand (HY-163610); Blue: Cereblon ligand (HY-A0003); Black: linker (HY-163647)).
For research use only. We do not sell to patients.
- Formula: C45H43N7O10
- Molecular Weight:841.86
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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
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
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AKR1C3 |
PROTAC AKR1C3 degrader-1 (Protac 5) potently inhibits purified recombinant AKR1C3 with an IC50 of 77 nM, and exhibits a selectivity of up to 116-fold over AKR1C1/2[1].
PROTAC AKR1C3 degrader-1 (1 nM-1 μM; 4-72 h) induces time- and concentration-dependent proteasome-mediated degradation of AKR1C3, ARv7 and AKR1C1/2 in 22Rv1 prostate cancer cells, with DC50 values of 52 nM, 70 nM and 49 nM respectively at 72 h[1].
PROTAC AKR1C3 degrader-1 (0.001-10 μM; 72 h) significantly reduces the viability of conventionally cultured 22Rv1 prostate cancer cells; at a concentration of 1 μM, this compound enhances cellular sensitivity to Enzalutamide (HY-70002)[1].
PROTAC AKR1C3 degrader-1 (0.001-10 μM; 72 h) causes a significant dose-dependent reduction in cell viability of AKR1C3-high-expressing 22Rv1 prostate cancer cells cultured in CSS; at a concentration of 0.1 μM, this compound enhances cellular sensitivity to Enzalutamide; it exerts no effect on the cell viability of AKR1C3-deficient LNCaP prostate cancer cells[1].
PROTAC AKR1C3 degrader-1 (0.001-10 μM; 72 h) induces a significant, dose-dependent decrease in cell viability in LNCaP1C3 prostate cancer cells overexpressing AKR1C3[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:22Rv1 prostate cancer cells
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Concentration:1 nM (time-course analysis)
10 nM (time-course analysis, proteasome inhibition study and hook effect analysis) -
Incubation Time:0, 2, 4, 6, 12, 16, 24, 48, 72 h (time-course analysis)
4 h (proteasome inhibition study)
72 h (hook effect analysis, DC50 determination) -
Result:Induced time-dependent AKR1C3 reduction starting at 24 h at 1 nM, though not significant.
Caused significant AKR1C3 degradation from 4 h post-treatment at 10 nM, reaching ~75% maximal degradation at 72 h.
Induced concomitant ARv7 degradation at 72 h and time-dependent AKR1C1/2 degradation to a lesser extent at 10 nM.
Exhibited a hook effect (reduced activity) at concentrations above 1 μM after 72 h.
Had DC50 values of 52 nM for AKR1C3, 49 nM for AKR1C1/2, and 70 nM for ARv7 after 72 h treatment.
Induced significantly greater AKR1C3 degradation than small molecule inhibitors 3 and 4 at 10 nM for 72 h.
Had its AKR1C3 degradation effect blocked by pretreatment with 3 μM MG132 (HY-13259) for 2 h when used at 10 nM for 4 h.
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Cell Line:22Rv1 prostate cancer cells (standard culture media, moderate AKR1C3 expression)
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Concentration:0.001, 0.01, 0.1, 1, 10 μM (alone)
1 μM (in combination with 25 μM Enzalutamide) -
Incubation Time:72 h
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Result:Caused significant loss of cell viability at 0.01, 0.1, and 10 μM.
Showed no significant cell viability reduction at 1 μM, likely due to the hook effect.
Combined with 25 μM enzalutamide at 1 μM resulted in significant cell viability reduction, overcoming enzalutamide resistance.
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Cell Line:22Rv1 prostate cancer cells (charcoal-stripped serum media, high AKR1C3 expression), LNCaP prostate cancer cells (AKR1C3 null)
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Concentration:0.001, 0.01, 0.1, 1, 10 μM (alone)
0.1 μM (in combination with 25 μM Enzalutamide) -
Incubation Time:72 h
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Result:Induced significant, dose-dependent reduction in cell viability starting at 0.01 μM, with a 55% reduction at 10 μM.
Combined with 25 μM enzalutamide at 0.1 μM resulted in significant cell viability reduction, overcoming enzalutamide resistance.
Showed no observable reduction at any tested concentration in LNCaP prostate cancer cells.
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Cell Line:LNCaP1C3 prostate cancer cells (AKR1C3 stably transfected, high AKR1C3 expression)
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Concentration:0.001, 0.01, 0.1, 1, 10 μM
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Incubation Time:72 h
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Result:Induced dose-dependent reduction in cell viability at 1 and 10 μM.
Chemical Information
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Molecular Weight 841.86
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Formula C45H43N7O10
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SMILES
O=C(/C=C/C1=CC(C2=CC=CC=C2)=CC(C(NCC3=CC=C(C=C3)OCC4=CN(N=N4)CCOCCOCC(NC5=CC=CC6=C5CN(C6=O)C7CCC(NC7=O)=O)=O)=O)=C1)O
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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.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
PROTAC AKR1C3 degrader-1 Related Classifications
HY-163609 Related Classifications
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