Mineralization of cartilage and bone occurs by a series of physicochemical and biochemical processes that together facilitate the deposition of hydroxyapatite (HA) in specific areas of the extracellular matrix (ECM). Experimental evidence has pointed to the presence of HA crystals along collagen fibrils in the ECM and also within the lumen of chondroblast- and osteoblast-derived matrix vesicles more ..
Target
| Sequence: phosphatase, orphan 1 [Homo sapiens] Protein Family: Putative Phosphatase Gene:PHOSPHO1 |
Depositor Specified Assays
| AID | Name | Type | Comment |
|---|---|---|---|
| 1565 | uHTS absorbance assay for the identification of compounds that inhibit PHOSPHO1 | confirmatory | uHTS absorbance assay for the identification of compounds that inhibit PHOSPHO1. |
| 1056 | SAR analysis of an In Vitro TNAP Dose Response Luminescent Assay | confirmatory | Anti-target in Vitro TNAP Dose Response Luminescent Assay for SAR Study |
| 1535 | Confirmation of compounds inhibiting phosphomannose isomerase (PMI) via a fluorescence intensity assay. | confirmatory | Confirmation of compounds inhibiting phosphomannoseisomerase (PMI) via a fluorescence intensity assay |
| 1655 | Counter screen SAR assay for PMM2 inhibitors via a fluorescence intensity assay | confirmatory | Counter screen SAR assay for PMM2 inhibitors via a fluorescence intensity assay |
| 1666 | SAR assay for compounds that inhibit PHOSPHO1 | confirmatory | SAR assay for compounds that inhibit PHOSPHO1 |
Description:
Data Source: Sanford-Burnham Center for Chemical Genomics (SBCCG)
Source Affiliation: Sanford-Burnham Medical Research Institute (SBMRI, San Diego, CA)
Network: NIH Molecular Libraries Probe Production Centers Network (MLPCN)
Grant Number: 1 R03 MH084086-01
Assay Provider: Dr. Jose Luis Milan, Sanford-Burnham Medical Research Institute, San Diego CA
Mineralization of cartilage and bone occurs by a series of physicochemical and biochemical processes that together facilitate the deposition of hydroxyapatite (HA) in specific areas of the extracellular matrix (ECM). Experimental evidence has pointed to the presence of HA crystals along collagen fibrils in the ECM and also within the lumen of chondroblast- and osteoblast-derived matrix vesicles (MVs). Dr. Milan's working model is that bone mineralization is first initiated within the lumen of MVs. In a second step, HA crystals grow beyond the confines of the MVs and become exposed to the extracellular milieu where they continue to propagate along collagen fibrils. Recent data have indicated that tissue-nonspecific alkaline phosphatase (TNAP) plays a crucial role in restricting the concentration of extracellular inorganic pyrophosphate (PP), a mineralization inhibitor, to maintain a P/PPi ratio permissive for normal bone mineralization. Using a variety of single and double gene knockout experiments it has been found that mice deficient in TNAP function, i.e., Akp2-/- mice, display osteomalacia due to an arrest in the propagation of HA crystals outside the MVs caused by an increase in extracellular PPi concentrations. Inside the MVs, however, HA crystals are still present in Akp2-/- mice. It is hypothesize that a newly identified soluble phosphatase, PHOSPHO1, with specificity for phosphoethanolamine (PEA) and phosphoserine (PS) present in the MVs, is responsible for increasing the local concentration of Pi inside the MVs to change the P/PPi ratio to favor precipitation of HA seed crystals.
This AID summarizes the biological properties of the probe molecule, SID-57287582(ML086) characterized by a battery of secondary and counter assays(1056, 1535, 1565, 1655, 1666).
Source Affiliation: Sanford-Burnham Medical Research Institute (SBMRI, San Diego, CA)
Network: NIH Molecular Libraries Probe Production Centers Network (MLPCN)
Grant Number: 1 R03 MH084086-01
Assay Provider: Dr. Jose Luis Milan, Sanford-Burnham Medical Research Institute, San Diego CA
Mineralization of cartilage and bone occurs by a series of physicochemical and biochemical processes that together facilitate the deposition of hydroxyapatite (HA) in specific areas of the extracellular matrix (ECM). Experimental evidence has pointed to the presence of HA crystals along collagen fibrils in the ECM and also within the lumen of chondroblast- and osteoblast-derived matrix vesicles (MVs). Dr. Milan's working model is that bone mineralization is first initiated within the lumen of MVs. In a second step, HA crystals grow beyond the confines of the MVs and become exposed to the extracellular milieu where they continue to propagate along collagen fibrils. Recent data have indicated that tissue-nonspecific alkaline phosphatase (TNAP) plays a crucial role in restricting the concentration of extracellular inorganic pyrophosphate (PP), a mineralization inhibitor, to maintain a P/PPi ratio permissive for normal bone mineralization. Using a variety of single and double gene knockout experiments it has been found that mice deficient in TNAP function, i.e., Akp2-/- mice, display osteomalacia due to an arrest in the propagation of HA crystals outside the MVs caused by an increase in extracellular PPi concentrations. Inside the MVs, however, HA crystals are still present in Akp2-/- mice. It is hypothesize that a newly identified soluble phosphatase, PHOSPHO1, with specificity for phosphoethanolamine (PEA) and phosphoserine (PS) present in the MVs, is responsible for increasing the local concentration of Pi inside the MVs to change the P/PPi ratio to favor precipitation of HA seed crystals.
This AID summarizes the biological properties of the probe molecule, SID-57287582(ML086) characterized by a battery of secondary and counter assays(1056, 1535, 1565, 1655, 1666).
Protocol
See pertinent assays: 1056, 1535, 1565, 1655, 1666
Comment
Probe molecules are defined as the positives of this assay and assigned a score of 100
Result Definitions
| TID | Name | Description | Histogram | Type | Unit | |
|---|---|---|---|---|---|---|
| Outcome | The BioAssay activity outcome | Outcome | ||||
| Score | The BioAssay activity ranking score |  | Integer | |||
| 1 | ML# | ML# for the compound | String |
Additional Information
Grant Number: 1 R03 MH084086-01
Data Table (Concise)
Classification
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