JNJ-63576253 (TRC-253) is a potent and orally bioactive androgen receptor complete antagonist, with IC50s of 37 and 37 for F877L mutant AR and wild-type AR in LNCaP cells, respectively. 54 nM. JNJ-63576253 may be utilized in the research/study of castration-resistant prostate cancer (CRPC).

Physicochemical Properties

Molecular Formula	C23H22CLF3N6O2S
Molecular Weight	538.972992420197
Exact Mass	538.116
Elemental Analysis	C, 51.26; H, 4.11; Cl, 6.58; F, 10.57; N, 15.59; O, 5.94; S, 5.95
CAS #	2110428-64-1
Related CAS #	JNJ-63576253 free base;2110426-27-0
PubChem CID	130229811
Appearance	Off-white to light yellow solid powder
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	10
Rotatable Bond Count	4
Heavy Atom Count	36
Complexity	884
Defined Atom Stereocenter Count	0
InChi Key	QDINJYHLAKIZLE-UHFFFAOYSA-N
InChi Code	InChI=1S/C23H21F3N6O2S.ClH/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;1H
Chemical Name	5-[8-oxo-5-(6-piperidin-4-yloxypyridin-3-yl)-6-sulfanylidene-5,7-diazaspiro[3.4]octan-7-yl]-3-(trifluoromethyl)pyridine-2-carbonitrile;hydrochloride
Synonyms	JNJ63576253 HCl; JNJ63576253 hydrochloride, 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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.
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; once daily, face) greatly monitors the growth of tumors expressing LNCaP SRα F877L [1]. Targeting five androgen-sensitive organs (ASOs) activated by testosterone propionate (TP), JNJ-63576253 (30 mg/kg; po once daily for 10 days) [1]. JNJ-63576253 (10 mg/kg; po) exhibits simulated bioavailability (45%), Cmax ( JNJ-63576253 (2 mg/kg; i.v.) exhibits reasonable half-life (5.99 hours), CL (15.0 mL/min/kg) 0.66 μM) and AUClast (4.9 μg h/mL).
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.

Solubility Data

Solubility (In Vitro)

DMSO : ~250 mg/mL (~463.85 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (3.86 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (3.86 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. Solubility in Formulation 3: ≥ 2.08 mg/mL (3.86 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.8554 mL	9.2770 mL	18.5539 mL
	5 mM	0.3711 mL	1.8554 mL	3.7108 mL
	10 mM	0.1855 mL	0.9277 mL	1.8554 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.