JNJ-pan-AR
JNJ-pan-AR is an orally active androgen receptor (AR) inhibitor with an IC50 of 19 nM and a Ki of 8.4 nM against human wild-type AR. JNJ-pan-AR abolishes androgen-induced KLK2 and KLK3 mRNA expression and reduces androgen-dependent colony formation in prostate cancer cells. JNJ-pan-AR blocks AR nuclear translocation, inhibits PSA protein expression, and represses the growth of AR-dependent tumor cells and ARF877L-driven tumor xenografts. JNJ-pan-AR blocks transactivation and signaling of wild-type AR and various mutant AR variants. JNJ-pan-AR is applicable for research on castration-resistant prostate cancer.
For research use only. We do not sell to patients.
- CAS No.: 1332390-06-3
- Formula: C25H24F3N5O2S
- Molecular Weight:515.55
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
Biological Activity
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Cell Line
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Type | Value | Description | References |
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| VCaP | IC50 |
92 nM
Compound: 4; JNJ-pan-AR
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Antiproliferative activity against human VCaP cells expressing wild-type androgen receptor assessed as reduction in cell viability incubated for 5 days in presence of R1881 by CellTiter-glo assay
Antiproliferative activity against human VCaP cells expressing wild-type androgen receptor assessed as reduction in cell viability incubated for 5 days in presence of R1881 by CellTiter-glo assay
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[PMID: 33470111] |
JNJ-pan-AR (compound 4) potently and selectively binds to wild-type androgen receptor with an IC50 of 19 nM and a Ki of 8.4 nM, and has minimal affinity for glucocorticoid receptor[1].
JNJ-pan-AR acted as a complete antagonist in HepG2, LNCaP, and VCaP cells expressing wild-type and mutant androgen receptors such as F877L, L702H, T878A, W742C, and W875L, with no agonistic activity. Its IC50 values against HepG2 cells, LNCaP F877 cells, LNCaP AR cs cells, and wild-type AR VCaP cells transiently transfected with VP16-AR F877L were 127 nM, 98 nM, 191 nM, and 92 nM, respectively. It also effectively antagonized the transcriptional activity of various androgen receptor ligand-binding domain mutants in HepG2 cells[1].
JNJ-pan-AR potently blocks nuclear translocation of ARF877L mutant androgen receptor and inhibits PSA expression in LNCaP F877L cells, regardless of androgen stimulation[1].
JNJ-pan-AR inhibits androgen-stimulated nuclear translocation of wild-type androgen receptor in LNCaP cells[1].
JNJ-pan-AR (0.01-10 μM; 24 h) potently inhibits androgen-mediated KLK2 and KLK3 mRNA expression in LNCaP prostate cancer cells[2].
JNJ-pan-AR (0.062-1 μM; 14 day) inhibits androgen-driven colony formation in LNCaP prostate cancer cells[2].
JNJ-pan-AR (10 μM; >3 months chronic exposure, continuous maintenance) generates LNCaP JNJR prostate cancer cells with acquired resistance to JNJ-pan-AR, characterized by altered morphology and reduced growth rate[2].
JNJ-pan-AR (0.1-10 μM; 14 day) shows that exogenous AKR1C3 expression induces partial resistance to JNJ-pan-AR in LNCaP prostate cancer cells[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:LNCaP (AR-mutant T877A) prostate cancer cells
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Concentration:0.01 μM, 0.1 μM, 1 μM, 10 μM
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Incubation Time:24 h
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Result:Suppressed androgen-mediated induction of KLK2 and KLK3 mRNA expression in a concentration-dependent manner.
Reduced KLK2 mRNA fold change to ~15 (from ~50 with DMSO + R1881) at 10 μM.
Reduced KLK3 mRNA fold change to ~6 (from ~14 with DMSO + R1881) at 10 μM.
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Cell Line:LNCaP (AR-mutant T877A) prostate cancer cells
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Concentration:0.062 μM, 0.125 μM, 0.250 μM, 0.500 μM, 1 μM
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Incubation Time:14 day
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Result:Inhibited androgen-mediated colony formation efficiency in a concentration-dependent manner.
Reduced relative colony number to near baseline levels (comparable to cells treated with DMSO without R1881) at 1 μM.
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Cell Line:AKR1C3-overexpressing LNCaP (LNCaP AKR1C3) prostate cancer cells, vector control LNCaP Puro cells
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Concentration:0.1 μM, 1 μM, 10 μM
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Incubation Time:14 day
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Result:Resulted in significantly higher colony formation efficiency in LNCaP AKR1C3 cells than LNCaP Puro cells at all tested concentrations.
Achieved a relative colony number (normalized to DMSO) of ~0.45 for LNCaP AKR1C3 cells at 0.1 μM.
Achieved a relative colony number (normalized to DMSO) of ~0.4 for LNCaP AKR1C3 cells at 10 μM.
JNJ-pan-AR (30 mg/kg; p.o.; daily; 10 days) potently inhibits testosterone propionate-stimulated androgen-sensitive organ growth in mice[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:SHO (male, castrated)[1]
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Dosage:10 mg/kg; 30 mg/kg
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Administration:p.o.; daily
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Result:Achieved a tumor growth inhibition (TGI) of 80.2%.
Achieved a TGI of 100.8% (complete tumor growth stasis).
Reached a plasma exposure of 748 ng/mL.
Chemical Information
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CAS No. 1332390-06-3
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Molecular Weight 515.55
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Formula C25H24F3N5O2S
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SMILES
N#CC1=NC=C(N2C(C3(CCC3)N(C2=S)C4=CC=C(C=C4)OC5CCN(CC5)C)=O)C=C1C(F)(F)F
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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
[1]. Zhang Z, et al. Discovery of JNJ-63576253: A Clinical Stage Androgen Receptor Antagonist for F877L Mutant and Wild-Type Castration-Resistant Prostate Cancer (mCRPC). J Med Chem. 2021;64(2):909-924. [Content Brief]
[2]. Hertzog JR, et al. AKR1C3 mediates pan-AR antagonist resistance in castration-resistant prostate cancer. Prostate. 2020;80(14):1223-1232. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)