Physicochemical Properties
| Molecular Formula | C23H21F3N6O2S |
| Molecular Weight | 502.5121 |
| Exact Mass | 502.14 |
| Elemental Analysis | C, 54.97; H, 4.21; F, 11.34; N, 16.72; O, 6.37; S, 6.38 |
| CAS # | 2110426-27-0 |
| Related CAS # | JNJ-63576253;2110428-64-1 |
| PubChem CID | 130229812 |
| Appearance | Solid powder |
| LogP | 3 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 10 |
| Rotatable Bond Count | 4 |
| Heavy Atom Count | 35 |
| Complexity | 884 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | OUEHJEYKNYQVRC-UHFFFAOYSA-N |
| 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 |
| 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 |
| Synonyms | TRC253; TRC-253; TRC 253; JNJ63576253; JNJ 63576253; JNJ 63576253; |
| HS Tariff Code | 2934.99.9001 |
| 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) |
Biological Activity
| 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]. |
| 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]. |
| 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. |
| References |
[1]. 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 Jan 28;64(2):909-924. |
| Additional Infomation | Androgen Receptor Antagonist TRC253 is an orally bioavailable androgen receptor (AR) antagonist, with potential antineoplastic activity. Upon oral administration, AR antagonist TRC253 specifically binds to both wild-type and certain mutant forms of AR, thereby preventing androgen-induced receptor activation and facilitating the formation of inactive complexes that cannot translocate to the nucleus. This prevents binding to and transcription of AR-responsive genes, inhibits the expression of genes that regulate prostate cancer cell proliferation, and may lead to an inhibition of growth of tumor cells in which AR is overexpressed and/or mutated. AR is often overexpressed and/or mutated in prostate cancers and plays a key role in proliferation, survival and chemoresistance of tumor cells. |
Solubility Data
| 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 |
| 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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (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 |