| http://purl.uniprot.org/citations/33741272 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/33741272 | http://www.w3.org/2000/01/rdf-schema#comment | "Propionic Acidemia (PA) and Methylmalonic Acidemia (MMA) are inborn errors of metabolism affecting the catabolism of valine, isoleucine, methionine, threonine and odd-chain fatty acids. These are multi-organ disorders caused by the enzymatic deficiency of propionyl-CoA carboxylase (PCC) or methylmalonyl-CoA mutase (MUT), resulting in the accumulation of propionyl-coenzyme A (P-CoA) and methylmalonyl-CoA (M-CoA in MMA only). Primary metabolites of these CoA esters include 2-methylcitric acid (MCA), propionyl-carnitine (C3), and 3-hydroxypropionic acid, which are detectable in both PA and MMA, and methylmalonic acid, which is detectable in MMA patients only (Chapman et al., 2012). We deployed liver cell-based models that utilized PA and MMA patient-derived primary hepatocytes to validate a small molecule therapy for PA and MMA patients. The small molecule, HST5040, resulted in a dose-dependent reduction in the levels of P-CoA, M-CoA (in MMA) and the disease-relevant biomarkers C3, MCA, and methylmalonic acid (in MMA). A putative working model of how HST5040 reduces the P-CoA and its derived metabolites involves the conversion of HST5040 to HST5040-CoA driving the redistribution of free and conjugated CoA pools, resulting in the differential reduction of the aberrantly high P-CoA and M-CoA. The reduction of P-CoA and M-CoA, either by slowing production (due to increased demands on the free CoA (CoASH) pool) or enhancing clearance (to replenish the CoASH pool), results in a net decrease in the CoA-derived metabolites (C3, MCA and MMA (MMA only)). A Phase 2 study in PA and MMA patients will be initiated in the United States."xsd:string |
| http://purl.uniprot.org/citations/33741272 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.ymgme.2021.03.001"xsd:string |
| http://purl.uniprot.org/citations/33741272 | http://purl.uniprot.org/core/author | "Chapman K.A."xsd:string |
| http://purl.uniprot.org/citations/33741272 | http://purl.uniprot.org/core/author | "Hamilton C.A."xsd:string |
| http://purl.uniprot.org/citations/33741272 | http://purl.uniprot.org/core/author | "Olson M.W."xsd:string |
| http://purl.uniprot.org/citations/33741272 | http://purl.uniprot.org/core/author | "Figler R.A."xsd:string |
| http://purl.uniprot.org/citations/33741272 | http://purl.uniprot.org/core/author | "Wamhoff B.R."xsd:string |
| http://purl.uniprot.org/citations/33741272 | http://purl.uniprot.org/core/author | "Armstrong A.J."xsd:string |
| http://purl.uniprot.org/citations/33741272 | http://purl.uniprot.org/core/author | "Henke B.R."xsd:string |
| http://purl.uniprot.org/citations/33741272 | http://purl.uniprot.org/core/author | "Johns B.A."xsd:string |
| http://purl.uniprot.org/citations/33741272 | http://purl.uniprot.org/core/author | "Reardon J.E."xsd:string |
| http://purl.uniprot.org/citations/33741272 | http://purl.uniprot.org/core/author | "Collado M.S."xsd:string |
| http://purl.uniprot.org/citations/33741272 | http://purl.uniprot.org/core/author | "Hoang S.A."xsd:string |
| http://purl.uniprot.org/citations/33741272 | http://purl.uniprot.org/core/author | "Pourtaheri T.D."xsd:string |
| http://purl.uniprot.org/citations/33741272 | http://purl.uniprot.org/core/author | "Summar M.M."xsd:string |
| http://purl.uniprot.org/citations/33741272 | http://purl.uniprot.org/core/date | "2021"xsd:gYear |
| http://purl.uniprot.org/citations/33741272 | http://purl.uniprot.org/core/name | "Mol Genet Metab"xsd:string |
| http://purl.uniprot.org/citations/33741272 | http://purl.uniprot.org/core/pages | "71-82"xsd:string |
| http://purl.uniprot.org/citations/33741272 | http://purl.uniprot.org/core/title | "A novel small molecule approach for the treatment of propionic and methylmalonic acidemias."xsd:string |
| http://purl.uniprot.org/citations/33741272 | http://purl.uniprot.org/core/volume | "133"xsd:string |
| http://purl.uniprot.org/citations/33741272 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/33741272 |
| http://purl.uniprot.org/citations/33741272 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/33741272 |
| http://purl.uniprot.org/uniprot/#_A0A0K0PWN6-mappedCitation-33741272 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/33741272 |
| http://purl.uniprot.org/uniprot/#_A0A024RD82-mappedCitation-33741272 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/33741272 |