| Identification | Back Directory | [Name]
JNJ-63576253(TRC-253) | [CAS]
2110428-64-1 | [Synonyms]
JNJ63576253 HCl
JNJ-63576253(TRC-253) | [Molecular Formula]
C23H22ClF3N6O2S | [MDL Number]
MFCD33548920 | [MOL File]
2110428-64-1.mol | [Molecular Weight]
538.97 |
| Chemical Properties | Back Directory | [storage temp. ]
Store at -20°C | [solubility ]
DMSO : 250 mg/mL (463.85 mM; Need ultrasonic) | [form ]
Solid | [color ]
Off-white to light yellow | [InChIKey]
QDINJYHLAKIZLE-UHFFFAOYSA-N | [SMILES]
O=C1N(C2=CN=C(C#N)C(C(F)(F)F)=C2)C(=S)N(C2=CN=C(OC3CCNCC3)C=C2)C21CCC2.Cl |
| Hazard Information | Back Directory | [Uses]
JNJ-63576253 (TRC-253) is a potent and orally active full antagonist of androgen receptor (AR), with IC50s of 37 and 54 nM for F877L mutant AR and wild-type AR in LNCaP cells. JNJ-63576253 can be used for the research of castration-resistant prostate cancer (CRPC)[1]. | [Biological Activity]
JNJ-63576253 (TRC-253) is a potent and orally active full antagonist of androgen receptor (AR), with IC50s of 37 and 54 nM for F877L mutant AR and wild-type AR in LNCaP cells. JNJ-63576253 can be used for the research of castration-resistant prostate cancer (CRPC)[1].
JNJ-63576253 (0.0003-100 μM; 5 d) inhibits the growth of VCaP cells, with an IC50 of 265 nM[1].JNJ-63576253 is stable in human liver microsomes, with an T1/2 of >180 min[1].
JNJ-63576253 (30 mg/kg; p.o. once daily for 72 days) significantly inhibits the growth of prostate LNCaP SRα F877L tumor in mice[1].JNJ-63576253 (30 mg/kg; p.o. once daily for 10 days) inhibits the five androgen sensitive organs (ASOs) under stimulation by testosterone propionate (TP) in mice[1].JNJ-63576253 (10 mg/kg; p.o.) exhibits moderate oral bioavailability (45%), Cmax (0.66 μM) and AUClast (4.9 μg?h/mL) in mice[1].JNJ-63576253 (2 mg/kg; i.v.) exhibits reasonable half-life (5.99 h), CL (15.0 mL/min/kg) and Vdss (6.11 L/kg) in mice[1]. | [in vivo]
JNJ-63576253 (30 mg/kg; p.o. once daily for 72 days) significantly inhibits the growth of prostate LNCaP SRα F877L tumor in mice[1].
JNJ-63576253 (30 mg/kg; p.o. once daily for 10 days) inhibits the five androgen sensitive organs (ASOs) under stimulation by testosterone propionate (TP) in mice[1].
JNJ-63576253 (10 mg/kg; p.o.) exhibits moderate oral bioavailability (45%), Cmax (0.66 μM) and AUClast (4.9 μg h/mL) in mice[1].
JNJ-63576253 (2 mg/kg; i.v.) exhibits reasonable half-life (5.99 h), CL (15.0 mL/min/kg) and Vdss (6.11 L/kg) in mice[1]. | Animal Model: | Castrated SHO mice with prostate LNCaP SRα F877L tumor[1] | | Dosage: | 30 mg/kg | | Administration: | P.o. once daily for 72 days | | Result: | Inhibited the tumor growth by 87%.
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| Animal Model: | CD-1 male mice[1] | | Dosage: | 2 mg/kg for i.v.; 10 mg/kg for p.o. (Pharmacokinetic Analysis) | | Administration: | Intravenous administration and oral administration | | Result: | I.v.: T1/2=5.99 h; CL=15.0 mL/min/kg; Vdss=6.11 L/kg.
P.o.: F=45%; Cmax=0.66 μM; AUClast=4.9 μg?h/mL.
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| [storage]
Store at -20°C | [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 Jan 28;64(2):909-924. |
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