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| 5mg |
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| Other Sizes |
Purity: ≥98%
MK-0429 is a compound that was originally developed as a selective and potent αvβ3 inhibitor for the treatment of osteoporosis, on renal function and fibrosis. MK-0429 is an equipotent pan-inhibitor of multiple av integrins. MK-0429 dose-dependently inhibited podocyte motility and also suppressed TGF-β-induced fibrosis marker gene expression in kidney fibroblasts. Moreover, in the obese ZSF1 rat model of diabetic nephropathy, chronic treatment with MK-0429 resulted in significant reduction in proteinuria, kidney fibrosis, and collagen accumulation. In summary, inhibition of multiple integrin subtypes might lead to meaningful impact on proteinuria and renal fibrosis in diabetic nephropathy.
| ln Vitro |
MK-0429 binds with high affinity to purified human, murine, and rat αvβ3 integrin, with equilibrium dissociation constants (Kd) of 0.33 ± 0.04 nM, 0.56 ± 0.07 nM, and 1.23 ± 0.11 nM, respectively[2]
MK-0429 blocks adhesion of HEK293-αvβ3 cells to vitronectin with an IC50 of 0.58 ± 0.30 nM[2] MK-0429 is approximately 100-fold less potent in blocking adhesion of HEK293 cells overexpressing αvβ5 integrin to vitronectin[2] MK-0429 is >1,000-fold less active in blocking adhesion functions mediated by integrins αIIbβ3 or α5β1 to fibrinogen or fibronectin, respectively[2] |
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| ln Vivo |
MK-0429 decreases the size and growth of metastatic tumor colonies in the lungs when taken orally twice daily for two weeks at a dose of 100 or 300 mg/kg. MK-0429 is safe and efficient in lowering the metastasis of lung melanoma [1].
In a melanoma lung metastasis prevention model, oral administration of MK-0429 at 100 mg/kg and 300 mg/kg twice daily significantly reduced the total number of metastatic lung colonies by 64% and 57%, respectively, compared to vehicle-treated mice[2] MK-0429 at 300 mg/kg twice daily also reduced the total tumor area in lungs by 60% compared to vehicle[2] In a separate study using B16F10-luciferase expressing cells and bioluminescent imaging, oral MK-0429 (300 mg/kg, twice daily) reduced the progression of ventral and dorsal lung metastases by 22% and 38%, respectively, by study completion (day 15) compared to vehicle[2] Ex vivo bioluminescent analysis and manual colony counting showed that MK-0429 treatment (300 mg/kg, twice daily for two weeks) reduced lung metastasis by approximately 30-40% compared to vehicle[2] Unlike cyclophosphamide (a positive control), treatment with MK-0429 did not lead to significant body weight loss in mice, indicating a favorable safety profile in this model[2] |
| Enzyme Assay |
The affinity of radiolabeled MK-0429 for various integrins was determined by binding assays using purified receptors[2]
Purified human, murine, and rat αvβ3 integrin receptors were used in these binding studies[2] |
| Cell Assay |
Human embryonic kidney 293 (HEK293) cells were stably co-transfected to overexpress specific human integrins (αvβ3, αvβ5, αIIbβ3, or α5β1)[2]
For cell adhesion assays, 25 x 10³ cells per well were added to microtiter wells coated with specific ligands: vitronectin (for αvβ3 and αvβ5), fibrinogen (for αIIbβ3), or fibronectin (for α5β1)[2] Cells were allowed to attach for 2 hours at 37°C in a humidified incubator in the absence or presence of increasing concentrations of MK-0429[2] Non-attached cells were gently washed away. Attached cells were quantified by colorimetric detection of hexosaminidase enzymatic activity using a microplate reader[2] The number of attached cells was determined using a standard curve for each cell line and expressed as the mean of triplicate samples[2] |
| Animal Protocol |
Animal/Disease Models: B6D2F1 hybrid female mice [2]
Doses: 100 or 300 mg/kg Route of Administration: Orally, twice (two times) daily (bid), 2 weeks Experimental Results: MK-0429 at 100 and 300 mg/kg will metastasize The number of tumor colonies was diminished compared with vehicle, and the tumor area was diminished by 64% and 57% respectively at high doses [2]. Experiment 1 (Prevention Model): Female B6D2F1 mice (6-week-old) received an intravenous tail vein injection of 1.5 x 10⁵ murine B16F10 melanoma cells[2] One day after tumor cell injection, mice were treated orally with vehicle (saline), MK-0429 (100 or 300 mg/kg, twice daily), or cyclophosphamide (300 mg/kg, intraperitoneally, once daily) for approximately two weeks[2] Body weight was recorded daily. Necropsy was performed when control mice developed approximately 100 lung metastases. Lung surfaces were dissected and melanoma colonies were counted manually[2] For histological analysis, lungs were fixed, embedded, sectioned, and stained with hematoxylin and eosin. Tumor area was quantified using image analysis software[2] Experiment 2 (De Novo Progression Model): Female athymic (nu/nu) mice (8-week-old) received an intravenous tail vein injection of 2.5 x 10⁵ B16F10 melanoma cells stably expressing luciferase (B16F10-luc)[2] One day post-injection, mice were treated orally with vehicle or MK-0429 (300 mg/kg, twice daily) for two weeks[2] Bioluminescence imaging was performed twice weekly using an in vivo imaging system. Mice were anesthetized and injected with D-luciferin intraperitoneally before imaging[2] At study end, mice were sacrificed, lungs were collected, and ex vivo bioluminescent imaging and manual colony counting were performed[2] |
| ADME/Pharmacokinetics |
Metabolism / Metabolites
MK-429's known human metabolites include 3-[3-[3-(7-hydroxy-5,6,7,8-tetrahydro-1,8-naphthidin-2-yl)propyl]-2-oxoimidazolidine-1-yl]-3-(6-oxo-1H-pyridin-3-yl)propionic acid, 3-(6-oxo-1H-pyridin-3-yl)-3-[2-oxo-3-[3-(5,6,7,8-tetrahydro-1,8-naphthidin-2-yl)propyl]imidazolidine-1-yl]propionic acid, and 3-[3-[3-(5-hydroxy-5,6,7,8-tetrahydro-1,8-naphthidin-2-yl)propyl]-2-oxoimidazolidine-1-yl]-3-(6-oxo-1H-pyridin-3-yl)propionic acid. The literature indicates that MK-0429 is an orally bioavailable molecule. [3] The literature does not describe other specific ADME/PK parameters (e.g., absorption, distribution, metabolism, excretion, half-life, oral bioavailability). [3] |
| Toxicity/Toxicokinetics |
In a mouse B16F10 melanoma model, oral administration of MK-0429 at doses of 100 and 300 mg/kg twice daily did not cause significant weight loss during the study period, unlike cyclophosphamide, which caused an initial weight loss of 9–11% [2]. Previous clinical studies cited in the literature showed that MK-0429 was well tolerated in male prostate cancer patients at doses up to 1600 mg twice daily for four weeks and in postmenopausal women with osteoporosis for 12 months without serious adverse events [2].
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| References |
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| Additional Infomation |
MK-0429 is a small molecule integrin αvβ3 inhibitor with high oral activity and selectivity[2]. It was originally developed for the treatment of osteoporosis, and clinical trials have shown that it can effectively improve bone mineral density[2]. Based on the role of integrin αvβ3 in tumor progression, angiogenesis and metastasis, this study explores its application in the prevention of melanoma metastasis[2]. The compound exhibits good selectivity, with significantly higher inhibitory activity against αvβ3 than against related integrins αvβ5, αIIbβ3 and α5β1[2]. Studies have shown that MK-0429 has good oral bioavailability and established safety, and is expected to become a candidate drug for early intervention to prevent systemic spread of melanoma, and may be used in combination with standard therapy[2].
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| Molecular Formula |
C23H29N5O4
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| Molecular Weight |
439.51
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| Exact Mass |
439.221
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| CAS # |
227963-15-7
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| Related CAS # |
477841-10-4 (5 hydrate);227963-15-7;477841-08-0 (2 hydrate);477841-09-1 (4 hydrate); 1125471-59-1 (0.5 hydrate);
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| PubChem CID |
9853559
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| Appearance |
White to off-white solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
699.0±55.0 °C at 760 mmHg
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| Flash Point |
376.5±31.5 °C
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| Vapour Pressure |
0.0±2.3 mmHg at 25°C
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| Index of Refraction |
1.606
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| LogP |
2.9
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
32
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| Complexity |
650
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| Defined Atom Stereocenter Count |
1
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| SMILES |
COC1=NC=C(C=C1)[C@H](CC(=O)O)N2CCN(C2=O)CCCC3=NC4=C(CCCN4)C=C3
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| InChi Key |
HGFOOLONGOBCMP-IBGZPJMESA-N
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| InChi Code |
InChI=1S/C23H29N5O4/c1-32-20-9-7-17(15-25-20)19(14-21(29)30)28-13-12-27(23(28)31)11-3-5-18-8-6-16-4-2-10-24-22(16)26-18/h6-9,15,19H,2-5,10-14H2,1H3,(H,24,26)(H,29,30)/t19-/m0/s1
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| Chemical Name |
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| Synonyms |
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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 |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.62 mg/mL (5.96 mM) (saturation unknown) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
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 (4.73 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. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (4.73 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. Solubility in Formulation 4: ≥ 2.08 mg/mL (4.73 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 corn oil and mix evenly. Solubility in Formulation 5: 7.14 mg/mL (16.25 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication (<60°C). |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2753 mL | 11.3763 mL | 22.7526 mL | |
| 5 mM | 0.4551 mL | 2.2753 mL | 4.5505 mL | |
| 10 mM | 0.2275 mL | 1.1376 mL | 2.2753 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.
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