BMS-564929

Androgen receptor (Ki = 2.11±0.16 nM)

In C2C12 myoblast cell lines, BMS-564929 showed an efficacy of 0.44±0.03 nM (EC50), which is the dose at which 50% of the maximal stimulatory action of DHT is attained. BMS-564929's EC50 in PEC cell lines is 8.66 ± 0.22 nM. BMS-564929 exhibits a periodicity on AR greater than 1000 times that of progesterone receptor (PR), glucocorticoid receptor (GR), mineralocorticoid receptor (MR), and estrogen receptors (ER) α and β. 400 times or such. At doses up to 30 μM, BMS-564929 demonstrated no detectable activity in functional transactivation tests of ERα/β, GR, MR, or PR [1].

BMS-564929 (po) shown noticeably more potent activity in the levator ani muscle in sexually mature, castrated sales; the net height of the dissected mesh with the forceps is 160 times; the levator ani muscle had an ED50 of 0.0009 mg/kg and an ED50 of 0.14 mg. At 0.1 mg/kg, about 100% stimulation was obtained; at 0.3 and 1 mg/kg, more than 125% stimulation was obtained. BMS-564929 is more than 200 times more effective in triggering dissection and 80 times more potent in dissection and dissection when compared to T propionate (TP) in the same mouse [1].

The human cancer epithelial breast cell lines MDA MB-453 and T47D are used in radioligand competition binding assays. These cell lines express AR and progesterone receptor (PR) respectively, endogenously. BMS-564929 is infused with [3H]DHT or [3H]progesterone at different concentrations and incubated with the cells for two hours at room temperature in order to perform binding assays. Enterokinase cleavage site, maltose binding protein, a particular biotinylation sequence, and either the ERα or ERβ LBD are used in fusion proteins for ERα and ERβ that are expressed in Escherichia coli. For two hours at room temperature, BMS-564929 and [3H]E2 are incubated with ERα and ERβ LBD to carry out binding reactions. Kidney cytosolic preparations and [3H]aldosterone are used in the competition binding assay to assess BMS-564929's specific binding activity to the mineralocorticoid receptor (MR). To increase the concentration of MR in the cytosol of kidney cells and eliminate the endogenous source of aldosterone, rats with adrenalectomies are used to harvest their kidneys. To prevent nonspecific binding to the glucocorticoid receptor (GR), binding reactions are incubated on ice for two hours while excess mifepristone (RU486) is present. According to the manufacturer's instructions, GR binding is measured using a fluorescence polarization based assay. Test compound inhibition of natural ligand binding at various concentrations is used to compute inhibitory constants (Ki, app), which characterize the apparent binding affinity of the test compounds to intracellular receptors. Standard charcoal assay is used to perform SHBG binding. 1. mg of lyophilized SHGB powder (Tris), 0.4% Dextran, 3% charcoal, and [3H]DHT in PBS arethe reagents; the binding buffer consists of 50 mM Tris, pH 7.6, 100 mM NaCl, 1 mM EDTA, and 1 mM DTT, along with a mock lysate (3.5 μg/100 μL buffer); the stock solutions are 1 mg/mL in water equals 20 μM for the stock SHBG protein [3H]. BMS 564929: 10 mM in DMSO; DHT: 10 mM; DHT ligand: 9 μM. In a 200 μL volume, compounds diluted in binding buffer are added to 40 nM [3H]DHT and 20 nM SHBG protein. The mixture is then incubated for one hour at room temperature. In 200 μL volume, there was total binding of 40 nM [3H]DHT and 20 nM SHBG protein; nonspecific binding involved 40 nM [3H]DHT and 20 nM SHBG protein along with 1 mM cold DHT. Following the incubation period, 200 μL of the charcoal solution (3% with 0.04% dextran) is combined with 200 μL of the reactions, and the mixture is shaken for 15 minutes prior to centrifugation. Next, 200 μL of supernatant is poured into each well of a 24-well white Optiplate, and mixing is done before adding 200 μL of scintillant. Topcount is used to read radioactivity counts[1].

Rats :Matched sets of sexually mature, 42-56-day-old, 200-250 g Harlan Sprague Dawley rats are given BMS-564929 (0.00001-10 mg/kg) orally once a day for 14 days via oral gavage in a solution/suspension of 80% PEG 400 and 20% Tween 20. Starting on day 15 following surgery, two control groups—one castrated and the other sham operated intact—are given oral doses of the PEG/TW vehicle exclusively. The dosage for animals is 1 mL/kg body weight (vol/wt). As a reference compound, T propionate (TP) is dosed once daily sc in a vehicle consisting of 90% peanut oil and 10% ethanol (0.03–10 mg/kg). Serum is taken for LH measurements, the levator ani and ventral prostate are surgically removed and weighed, and the animals are killed by carbon dioxide asphyxiation after 14 days of treatment.

[1]. Ostrowski J, et al. Pharmacological and x-ray structural characterization of a novel selective androgen receptor modulator: potent hyperanabolic stimulation of skeletal muscle with hypostimulation of prostate in rats. Endocrinology. 2007 Jan;148(1):4-12

C14H12N3O3CL

305.71638

305.06

C, 55.00; H, 3.96; Cl, 11.60; N, 13.75; O, 15.70

627530-84-1

627530-84-1

Solid powder

CC1=C(C=CC(=C1Cl)C#N)N2C(=O)[C@@H]3[C@@H](CCN3C2=O)O

KEJORAMIZFOODM-PWSUYJOCSA-N

InChI=1S/C14H12ClN3O3/c1-7-9(3-2-8(6-16)11(7)15)18-13(20)12-10(19)4-5-17(12)14(18)21/h2-3,10,12,19H,4-5H2,1H3/t10-,12+/m1/s1

4-[(7R,7aS)-7-hydroxy-1,3-dioxo-5,6,7,7a-tetrahydropyrrolo[1,2-c]imidazol-2-yl]-2-chloro-3-methylbenzonitrile

BMS 564929; BMS564929; BMS-564929

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO: ~50 mg/mL (~163.56 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (8.18 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 25.0 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.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (8.18 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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)