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Blood was collected into glass vials in the absence of anticoagulant and allowed to coagulate for 30 min at room temperature. Serum was dispensed into glass vials and centrifuged at 2100g at room temperature for 10\u202fmin to remove any traces of coagulated blood. Serum was harvested into glass vials and stored at \u221280\u00b0\u202fC until required. Human serum samples were incubated in the presence of test compound over the concentration range 0.5\u202fnM to 10\u202f\u03bcM in a shaking incubator at 37\u00b0\u202fC for three hours. Extraction of LPA was undertaken by a solvent precipitation approach. 50\u202f\u00b5L of serum prepared as described above was precipitated with 400\u202f\u00b5L of methanol containing 30\u202fmM citric acid and the internal standard (0.5\u202f\u00b5M LPA 17:0). Samples were shaken at 1300\u202frpm for 1\u202fmin and then centrifuged at 2100g at 4\u00b0\u202fC for 20 min. The supernatant was removed for analysis by LC-MS\/MS. Extraction of calibration standards and serum samples was undertaken in 96-well glass coated microtitre plates. LC-MS\/MS analysis was performed using an Acquity UPLC (Waters, UK) and an API4000 Sciex tandem mass spectrometer (AB Sciex, USA) equipped with an electrospray ionisation source. LPA isoforms were analysed using an Acquity UPLC BEH C18 column (1.7\u202f\u00b5m particle size; 50\u202f\u00d7\u202f2.1 mm; Waters, UK) maintained at 60\u00b0\u202fC. The mobile phase consisted of solvent A (50\u202f\u00b5M ammonium acetate with 1% triethylamine (TEA) in water) and solvent B (99% methanol, 1% TEA). The mobile phase was maintained at 70% B for 1.5\u202fmin; then a linear gradient from 70 to 95% B in 0.10\u202fmin; 95 % B for 0.90\u202fmin after which the gradient was returned to the initial conditions. Samples were detected using multiple reaction monitoring in negative ion mode. LPA concentration data was used to assess the degree of autotaxin inhibition by calculating IC50 values, by non-linear regression in Graphpad Prism v6.01."},{"key":"10.1016\/j.bmcl.2018.05.030_b0115","unstructured":"Male Sprague-Dawley rats (n\u202f=\u202f6 per group) were dosed orally with test compound (made up in 0.5% methyl cellulose: 0.5% Tween80) or vehicle at a dose volume of 5 ml\/kg. At various time points after oral administration, blood samples (500\u202f\u00b5l) were collected from the tail vein and stored in glass vials in the absence of anti-coagulant. The blood samples were incubated at room temperature for 30\u202fmin and then centrifuged at 700g for 10\u202fmin. The serum was collected in glass coated 96 well plates and stored at \u221280\u202f\u00b0C until required for analysis. Bioanalysis was carried out as described in reference 21. The PK\/PD relationship was assessed using a PK\/PD link (PK 1-compartment; PD inhibitory effect Imax) model in Phoenix Winnonlin to derive in vivo IC50 values for each of the LPA isoforms."},{"key":"10.1016\/j.bmcl.2018.05.030_b0120","unstructured":"Compound 12 can be crystallised from hot butyl acetate."}],"container-title":["Bioorganic & Medicinal Chemistry Letters"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0960894X18304311?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0960894X18304311?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T07:24:11Z","timestamp":1760772251000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0960894X18304311"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,7]]},"references-count":29,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2018,7]]}},"alternative-id":["S0960894X18304311"],"URL":"https:\/\/doi.org\/10.1016\/j.bmcl.2018.05.030","relation":{},"ISSN":["0960-894X"],"issn-type":[{"value":"0960-894X","type":"print"}],"subject":[],"published":{"date-parts":[[2018,7]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Development of autotaxin inhibitors: A series of zinc binding triazoles","name":"articletitle","label":"Article Title"},{"value":"Bioorganic & Medicinal Chemistry Letters","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bmcl.2018.05.030","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2018 Elsevier Ltd. 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