| Size | Price | Stock | Qty |
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| 10mg |
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Purity: ≥98%
MK-0773 (PF-05314882) is a novel and potent SARM (selective androgen receptor modulator) that has the potential to prevent and treat muscle wasting linked to cancer. It binds to AR with an IC50 of 6.6 nM. Androgen receptor (AR) ligands that promote anabolism with diminished effects in reproductive tissues are known as selective androgen receptor modulators, or SARMs. SARMs completely, partially, or even antagonistically activate the AR in a variety of experimental settings; however, it is unknown how these intricate actions translate into tissue selectivity.
| Targets |
AR (IC50 = 6.6 nM)
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|---|---|
| ln Vitro |
MK-0773 binds to serum proteins as evidenced by its increased IC50 of 3.5 times when 3.5 percent rat serum and 13 times when 25% human serum are present. Using COS cells transfected with AR, the affinity of MK-0773 for AR is assessed across species. The IC50 values(0.50 nM for rats, 0.55 nM for dogs, 0.45 nM for rhesus, and 0.65 nM for humans) in all four species are remarkably similar[1].
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| ln Vivo |
In the OVX rat model, MK-0773 (6 and 80 mg/kg, s.c.) causes exposure-related stimulatory effects on cortical BFR and LBM. MK-0773 has less of an impact on the prostate and raises the weight of seminal vesicles at doses of 5, 15, and 80 mg/kg, s.c. In OVX rats, MK-0773's partial agonism and tissue selectivity do not result in different effects on lipid metabolism[1].
MK-0773 was dosed subcutaneously for 24 days in the OVX rat model (6 and 80 mg/kg) and produced plasma exposures over 24 h of 6.6 and 62 μm·h (Fig. 5b). This treatment produced exposure-related stimulatory effects on cortical BFR and LBM. The maximal anabolic effects of MK-0773 were equivalent to the SARM TFM-4AS-1 and ∼80% of 3 mg/kg DHT. Both MK-0773 and TFM-4AS-1 had <5% of the effect on uterus weight, and about 30–50% of the increase of sebaceous gland area produced by 3 mg/kg DHT. Next, ORX male rats were treated with daily subcutaneous dosing with MK-0773 (5, 15, and 80 mg/kg) for 17 days. The treatments produced plasma exposures over 24 h of 3, 10, and 56 μm·h. At the highest exposure tested, MK-0773 increased seminal vesicle weights by 12% that achieved by 3 mg/kg DHT (Fig. 5c and Table 2) and had similarly reduced effects on the prostate (data not shown). Taken together, MK-0773 exhibits the profile of an anabolic SARM with limited effects on the sebaceous glands and reproductive tracts of OVX and ORX rats[1]. Effect of MK-0773 and 2-FPA on Cholesterol In humans anabolic androgens reduce high density lipoprotein cholesterol by mechanisms that are not understood but have been proposed to reflect changes in lipid metabolism in adipose tissue. We, thus, asked if SARMs developed by our method would also reduce cholesterol levels in preclinical models. Treatments of OVX rats with MK-0773, 2-FPA, TFM-4AS-1, and DHT at anabolic doses for 24 days resulted in a similar decline in both total cholesterol and high density lipoprotein by 25–37% (Table 3). Thus, the partial agonism and tissue selectivity of MK-0773 does not translate into differential effects on lipid metabolism in OVX rats[1]. |
| Enzyme Assay |
Binding and Transcription Assays[1]
Binding and transactivation assays used the human breast carcinoma cell line MDA-MB-453, which expresses endogenous AR. ARBIND assays with 0.5 nm [3H]methyltrienolone (R1881, a potent AR agonist) were as previously described. TAMAR assays (transactivation modulation of AR) in 96-well plates used transient transfection of a modified mouse mammary tumor virus (MMTV) long terminal repeat promoter upstream of luciferase (MMTV-LUC). This MMTV has two direct repeat copies of a consensus glucocorticoid receptor response element between positions −88 and −190; these sequences are also recognized by AR. The VIRCON (virilization counterscreen) assay, which measures the AR N-terminal domain/ligand binding domain (LBD) interaction (N/C) of rhesus AR (rhAR), was evaluated by a mammalian two-hybrid assay in CV1 cells as detailed in Schmidt et al. The N/C interaction was evaluated as a ligand-mediated increase of luciferase reporter activity. The TRAF2 (transcriptional recruitment to AF2) assay, which measures the activation mediated by the AF-2 domain and potentiated by the full-length rat GRIP-1 coactivator, was measured by a mammalian two-hybrid assay in similar manner to the VIRCON assay. The Gal4-DNA binding domain was fused with the LBD of rhAR (pm-rhAR-LBD, amino acids 637–895), and the VP16AD was fused to the rat GRIP-1 (pcDNA3-GRIP-1 plasmid). The luciferase reporter plasmid with 5 copies of GAL-4 DBD binding sites (Gal4 × 5X90-luciferase) was transfected into COS-1 cells with the pm-rhAR-LBD and pcDNA3-GRIP-1 plasmids, and the AF-2 function was evaluated as a ligand-dependent dose response. |
| Animal Protocol |
Rats: After an orchidectomy (ORX), 3–4-month-old, 250–300-g rats' prostate and seminal vesicles are examined. Following surgery, the animals receive daily subcutaneous injections of test compounds for a period of 17 days. The weight of the seminal vesicles (SVs) is compared to that of ORX rats that were treated with either vehicle or DHT as a positive control.
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| References | |
| Additional Infomation |
MK-0773 is under investigation in clinical trial NCT00529659 (A Study of the Safety and Efficacy of MK-0773 in Women With Sarcopenia (Loss of Muscle Mass)(mk-0773-005)).
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| Molecular Formula |
C27H34FN5O2
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|---|---|
| Molecular Weight |
479.589569568634
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| Exact Mass |
479.269
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| Elemental Analysis |
C, 67.62; H, 7.15; F, 3.96; N, 14.60; O, 6.67
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| CAS # |
606101-58-0
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| Related CAS # |
606101-58-0
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| PubChem CID |
11950726
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
754.2±60.0 °C at 760 mmHg
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| Flash Point |
409.9±32.9 °C
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| Vapour Pressure |
0.0±2.5 mmHg at 25°C
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| Index of Refraction |
1.632
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| LogP |
3.17
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
35
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| Complexity |
927
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| Defined Atom Stereocenter Count |
7
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| SMILES |
FC1C(N(C)[C@]2([H])CC[C@]3([H])[C@]([H])(CC[C@]4(C)[C@@H](C(N([H])CC5=NC6=C(C=CC=N6)N5[H])=O)CC[C@]43[H])[C@]2(C=1)C)=O
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| InChi Key |
GBEUKTWTUSPHEE-JWJWXJQQSA-N
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| InChi Code |
InChI=1S/C27H34FN5O2/c1-26-11-10-17-15(6-9-21-27(17,2)13-19(28)25(35)33(21)3)16(26)7-8-18(26)24(34)30-14-22-31-20-5-4-12-29-23(20)32-22/h4-5,12-13,15-18,21H,6-11,14H2,1-3H3,(H,30,34)(H,29,31,32)/t15-,16-,17-,18+,21+,26-,27+/m0/s1
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| Chemical Name |
(1S,3aS,3bS,5aR,9aS,9bS,11aS)-8-fluoro-N-(1H-imidazo[4,5-b]pyridin-2-ylmethyl)-6,9a,11a-trimethyl-7-oxo-2,3,3a,3b,4,5,5a,9b,10,11-decahydro-1H-indeno[5,4-f]quinoline-1-carboxamide
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| Synonyms |
MK0773; MK-0773; MK 0773; PF 05314882; CHEMBL3221237; 5730VNW22X; PF05314882; PF-05314882
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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: ~33.3 mg/mL (~69.5 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.21 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 (5.21 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 25.0 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.21 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0851 mL | 10.4256 mL | 20.8511 mL | |
| 5 mM | 0.4170 mL | 2.0851 mL | 4.1702 mL | |
| 10 mM | 0.2085 mL | 1.0426 mL | 2.0851 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT00529659 | Completed | Drug: Comparator: MK-0773 Drug: Comparator: Placebo |
Sarcopenia | Merck Sharp & Dohme LLC | October 2007 | Phase 2 |
| NCT01011725 | Completed | Drug: MK 0773 Drug: Placebo |
Osteoporosis | Merck Sharp & Dohme LLC | November 2005 | Phase 1 |
| NCT01017458 | Completed | Drug: MK0773 Drug: Comparator: placebo injection |
Healthy | Merck Sharp & Dohme LLC | June 2007 | Phase 1 |
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