| Size | Price | Stock | Qty |
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| 100mg |
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| 500mg |
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| Other Sizes |
| Targets |
JNJ-63576253 targets the androgen receptor (AR). It acts as a potent and orally active full antagonist of AR. In LNCaP cells, it demonstrates IC50 values of 37 nM for the F877L mutant AR and 54 nM for wild-type AR. This dual activity against both wild-type and clinically relevant mutant forms of AR is a key feature of this compound.
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| ln Vitro |
VCaP cell proliferation is inhibited by JNJ-63576253 (0.0003-100 μM; 5 d) with an IC50 of 265 nM[1]. In human liver microsomes with T1/2 > 180 minutes, JNJ-63576253 exhibits stability [1].
In vitro, JNJ-63576253 inhibits the growth of VCaP prostate cancer cells with an IC50 of 265 nM. It is stable in human liver microsomes, exhibiting a half-life (T1/2) of over 180 minutes. These data indicate potent anti-proliferative activity against AR-dependent cancer cell lines and favorable metabolic stability in human-derived liver preparations. |
| ln Vivo |
JNJ-63576253 (30 mg/kg; orally, once daily for 72 days) significantly inhibits the growth of mouse prostate LNCaP SRα F877L tumors [1]. JNJ-63576253 (30 mg/kg; orally, once daily for 10 days) inhibits five androgen-sensitive organs (ASOs) stimulated by testosterone propionate (TP) in mice [1]. JNJ-63576253 (10 mg/kg; po) exhibits moderate oral bioavailability (45%), Cmax (0.66 μM), and AUClast (4.9 μg·h/mL) in mice [1]. JNJ-63576253 (2 mg/kg; iv) exhibits reasonable half-life (5.99 hours), CL (15.0 mL/min/kg) and Vdss (6.11 L/kg) in mice [1].
In vivo, JNJ-63576253 demonstrated significant efficacy in mouse models. At an oral dose of 30 mg/kg once daily for 72 days, it achieved 87% tumor growth inhibition in a prostate LNCaP SRα F877L xenograft model. Additionally, at the same dose for 10 days, it inhibited five androgen-sensitive organs (ASOs) under testosterone propionate stimulation. |
| Enzyme Assay |
The in vitro enzymatic activity of JNJ-63576253 is typically assessed using cell-free kinase or radioligand binding assays with recombinant AR protein. Competitive binding experiments are performed to calculate its affinity and IC50 values against wild-type and mutant AR. Specific protocols are detailed in the primary literature.
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| Cell Assay |
The cellular activity of JNJ-63576253 is evaluated in AR-dependent prostate cancer cell lines, such as LNCaP and VCaP. Cells are treated with escalating concentrations of the compound for 5 days, and cell viability is measured to determine IC50 values for growth inhibition.
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| Animal Protocol |
Animal/Disease Models: Castrated SHO mice with prostate LNCaP SRα F877L tumors [1]
Doses: 30 mg/kg Route of Administration: Po, one time/day for 72 days Experimental Results: Inhibited tumor growth by 87%. Animal/Disease Models: CD-1 male mice [1] Doses: 2 mg/kg, intravenous (iv) (iv)injection; 10 mg/kg po (pharmacokinetic/PK/PK analysis) Route of Administration: intravenous (iv) (iv)and oral administration Experimental Results: Iv: T1 /2=5.99 h; CL=15.0 ml/min/kg; Vdss=6.11 liters/kg. Po: F=45%; Cmax=0.66μM; AUClast=4.9 μg·h/mL. The in vivo efficacy of JNJ-63576253 is evaluated in xenograft mouse models bearing AR-driven tumors. In a typical study, castrated SHO mice with prostate LNCaP SRα F877L tumors are administered the compound orally at 30 mg/kg once daily for 72 days, and tumor volume is measured to calculate tumor growth inhibition. |
| ADME/Pharmacokinetics |
JNJ-63576253 has a molecular formula of C23H21F3N6O7S and a molecular weight of 502.51. In mouse pharmacokinetic studies, oral administration at 10 mg/kg showed moderate bioavailability (45%), with a Cmax of 0.66 μM and AUClast of 4.9 μg·h/mL. Intravenous administration at 2 mg/kg exhibited a half-life of 5.99 hours, clearance of 15.0 mL/min/kg, and a volume of distribution of 6.11 L/kg.
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| Toxicity/Toxicokinetics |
Preclinical toxicity studies indicate that JNJ-63576253 is well-tolerated at efficacious doses in mouse models. As a clinical-stage compound, comprehensive toxicology profiling has been conducted as part of its development program, with no obvious toxicity reported in published preclinical studies.
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| References | |
| Additional Infomation |
The androgen receptor antagonist TRC253 is an orally bioavailable androgen receptor (AR) antagonist with potential antitumor activity. After oral administration, TRC253 specifically binds to wild-type and certain mutant AR cells, thereby preventing androgen-induced receptor activation and promoting the formation of an inactive complex that cannot translocate to the nucleus. This can prevent the binding and transcription of AR-responsive genes, inhibit the expression of genes regulating prostate cancer cell proliferation, and may lead to the suppression of the growth of AR-overexpressing and/or mutated tumor cells. AR is frequently overexpressed and/or mutated in prostate cancer and plays a crucial role in tumor cell proliferation, survival, and chemotherapy resistance.
JNJ-63576253 is also known as TRC-253. It is a clinical-stage compound discovered for the treatment of castration-resistant prostate cancer (CRPC). The compound is a full AR antagonist with a unique profile against both wild-type and mutant receptors, making it a valuable tool for studying AR biology and resistance mechanisms in prostate cancer. |
| Molecular Formula |
C23H21F3N6O2S
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|---|---|
| Molecular Weight |
502.5121
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| Exact Mass |
502.14
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| Elemental Analysis |
C, 54.97; H, 4.21; F, 11.34; N, 16.72; O, 6.37; S, 6.38
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| CAS # |
2110426-27-0
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| Related CAS # |
JNJ-63576253;2110428-64-1
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| PubChem CID |
130229812
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| Appearance |
Solid powder
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| LogP |
3
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
35
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| Complexity |
884
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
OUEHJEYKNYQVRC-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H21F3N6O2S/c24-23(25,26)17-10-15(13-29-18(17)11-27)31-20(33)22(6-1-7-22)32(21(31)35)14-2-3-19(30-12-14)34-16-4-8-28-9-5-16/h2-3,10,12-13,16,28H,1,4-9H2
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| Chemical Name |
5-(8-Oxo-5-(6-(piperidin-4-yloxy)pyridin-3-yl)-6-thioxo-5,7-diazaspiro[3.4]octan-7-yl)-3-(trifluoromethyl)-picolinonitrile
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| Synonyms |
TRC253; TRC-253; TRC 253; JNJ63576253; JNJ 63576253; JNJ 63576253;
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9900 mL | 9.9501 mL | 19.9001 mL | |
| 5 mM | 0.3980 mL | 1.9900 mL | 3.9800 mL | |
| 10 mM | 0.1990 mL | 0.9950 mL | 1.9900 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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