Size | Price | Stock | Qty |
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5mg |
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10mg |
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25mg |
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50mg |
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100mg |
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Purity: ≥98%
BMS-564929 is a novel, highly potent, orally bioactive, nonsteroidal, bioactive, oral, tissue-specific, androgen receptor (AR) modulator that has a Ki of 2.11±0.16 nM for androgen receptor (AR). Clinical trials are now being conducted on it to treat age-related functional decline. In vitro, BMS-564929 is a subnanomolar AR agonist that is very selective for the AR receptor relative to other steroid hormone receptors and doesn't significantly interact with aromatase or SHBG. BMS-564929 is significantly more effective than testosterone (T) at inducing the growth of the levator ani muscle, and unlike T, it is highly selective for muscle over prostate, according to dose response studies conducted in castrated male rats. Through the use of x-ray crystallography, significant distinctions between the binding interactions of BMS-564929 with the AR and native hormones were identified. These differences included the discovery of multiple distinct contacts situated in particular helices of the ligand binding domain that are crucial for the recruitment of coregulatory proteins. Other possible mechanistic explanations for the observed tissue selectivity of this special, orally active androgen are effectively ruled out by the results of further pharmaceutical studies. The strong oral activity and tissue selectivity demonstrated by BMS-564929 are anticipated to yield a clinical profile that provides the demonstrated beneficial effects of T in muscle and other tissues with a more favorable safety window, as big obstacles to the clinical use of T are worries about the possible hyperstimulatory effects on prostate and an inconvenient route of administration.
Targets |
Androgen receptor (Ki = 2.11±0.16 nM)
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ln Vitro |
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].
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ln Vivo |
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].
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Enzyme Assay |
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].
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Animal Protocol |
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.
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References |
[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
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Molecular Formula |
C14H12N3O3CL
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Molecular Weight |
305.71638
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Exact Mass |
305.06
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Elemental Analysis |
C, 55.00; H, 3.96; Cl, 11.60; N, 13.75; O, 15.70
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CAS # |
627530-84-1
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Related CAS # |
627530-84-1
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Appearance |
Solid powder
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SMILES |
CC1=C(C=CC(=C1Cl)C#N)N2C(=O)[C@@H]3[C@@H](CCN3C2=O)O
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InChi Key |
KEJORAMIZFOODM-PWSUYJOCSA-N
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InChi Code |
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
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Chemical Name |
4-[(7R,7aS)-7-hydroxy-1,3-dioxo-5,6,7,7a-tetrahydropyrrolo[1,2-c]imidazol-2-yl]-2-chloro-3-methylbenzonitrile
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Synonyms |
BMS 564929; BMS564929; BMS-564929
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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) |
DMSO: ~50 mg/mL (~163.56 mM)
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Solubility (In Vivo) |
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. 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.  (Please use freshly prepared in vivo formulations for optimal results.) |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 3.2710 mL | 16.3548 mL | 32.7097 mL | |
5 mM | 0.6542 mL | 3.2710 mL | 6.5419 mL | |
10 mM | 0.3271 mL | 1.6355 mL | 3.2710 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.