RP 59794
RP 59794 is a potent collagenase (collagenase) and broad-spectrum matrix metalloproteinase (MMP) inhibitor. The active stereoisomer of RP 59794 has a Ki of 13 nM against MMP-1 (with native collagen as substrate) and 45 nM (with a synthetic octapeptide as substrate). RP 59794 blocks and partially dissociates TIMP by binding to the active site of collagenase, specifically inhibits the collagen-transmigrating migration of osteoclasts and bone resorption on collagen-coated surfaces, but exerts no effect on cell migration in collagen-free environments, and acts in a time-dependent manner in bone tissues. RP 59794 can be used in studies of arthritis, periodontal disease, corneal ulcers and tumor invasion.
For research use only. We do not sell to patients.
- CAS No.: 132259-06-4
- Formula: C20H31N3O4
- Molecular Weight:377.48
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
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MMP-1 13 nM (Ki, with native collagen as substrate) |
MMP-1 45 nM (Ki, with a synthetic octapeptide as substrate) |
RP 59794 form A (18 h) potently inhibits purified porcine synovial cell collagenase (using [14C]-collagen as substrate) with a Ki of 13 nM, and exhibits 500-fold higher activity than form B[1].
RP 59794 Form A inhibits purified porcine synovial cell collagenase (using a synthetic octapeptide substrate) with a Ki value of 45 nM, while Form B is approximately 67-fold less potent[1].
Crystal form RP 59794 A exhibits selective inhibitory activity against porcine synovial cell collagenase compared with other metalloproteinases; in contrast, crystal form RP 59794 B potently inhibits neprilysin (Ki ~10 nM) with low activity against collagenase[1].
RP 59794 (5 min) stereoselectively inhibits the formation of TIMP-collagenase complexes. Among its stereoisomers, form A completely blocks complex formation at a concentration of 10-3 M, which is consistent with the stereoselectivity of its collagenase inhibition[1].
RP 59794 (0.001 M; 3 h) at a 1000-fold molar excess can partially dissociate preformed TIMP-collagenase complexes, achieving a dissociation rate of 20%-30% at 36°C[1].
RP 59794 (0.1-10 μM; overnight) inhibits resorption pit formation by non-separated rabbit osteocytes in a dose-dependent manner on collagen-coated, but not uncoated, dentine slices[2].
RP 59794 (10 μM; overnight) inhibits the formation of bone resorption lacunae by purified rabbit osteoclasts on collagen-coated dentine slices (but fails to exert this effect on uncoated dentine slices)[2].
RP 59794 (0.1-10 μM; overnight) dose-dependently inhibits the invasive ability of purified rabbit osteoclasts through collagen-coated membranes (but exerts no such effect on uncoated membranes)[2].
RP 59794 (25 μM; 4-24 h) induces extensive demineralized but undigested bone matrix within osteoclast resorption lacunae in mouse calvarial explants, with its maximal effect observed at 16-24 h[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:Purified rabbit osteoclasts
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Concentration:0.1, 1 and 10 μM
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Incubation Time:overnight
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Result:Dose-dependently inhibited the invasive ability of purified rabbit osteoclasts through collagen-coated membranes (but showed no such effect on uncoated membranes), with significant inhibition observed at 1 μM and 10 μM.
Chemical Information
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CAS No. 132259-06-4
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Molecular Weight 377.48
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Formula C20H31N3O4
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SMILES
O=C(NCC1=CC=CC=C1)[C@@H](C(C)C)NC([C@@H](CC(C)C)CC(NO)=O)=O
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Structure Classification
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Initial Source
Cladosporium cladosporioide
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
[1]. Lelièvre Y, et al. Low molecular weight, sequence based, collagenase inhibitors selectively block the interaction between collagenase and TIMP (tissue inhibitor of metalloproteinases). Matrix (Stuttgart, Germany). 1990 Oct;10(5):292-9. [Content Brief]
[2]. Sato T, et al. The migration of purified osteoclasts through collagen is inhibited by matrix metalloproteinase inhibitors. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 1998 Jan;13(1):59-66. [Content Brief]
[3]. Everts V, et al. Cysteine proteinases and matrix metalloproteinases play distinct roles in the subosteoclastic resorption zone. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 1998 Sep;13(9):1420-30. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
RP 59794 Related Classifications
HY-183378 Related Classifications
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