{"product_id":"m15046","title":"PRN1371","description":"\u003cp style=\"padding-left:1em;\"\u003ePRN1371 is an irreversible covalent FGFR1-4 kinase inhibitor, with IC50s of 0.6, 1.3, 4.1, 19.3 and 8.1 nM for FGFR1, 2, 3, 4 and CSF1R, respectively.\u003c\/p\u003e\u003cp\u003e\u003cstrong\u003eProduct information\u003c\/strong\u003e\u003c\/p\u003e\u003cp\u003e\u003cstrong\u003eCAS Number:\u003c\/strong\u003e 1802929-43-6\u003c\/p\u003e\u003cp\u003e\u003cstrong\u003eMolecular Weight:\u003c\/strong\u003e 561.46\u003c\/p\u003e\u003cp\u003e\u003cstrong\u003eFormula:\u003c\/strong\u003e C26H30Cl2N6O4\u003c\/p\u003e\u003cp style=\"text-indent:-1em;padding-left:1em;\"\u003e\u003cstrong\u003eChemical Name:\u003c\/strong\u003e 6-(2,6-dichloro-3,5-dimethoxyphenyl)-2-(methylamino)-8-{3-[4-(prop-2-enoyl)piperazin-1-yl]propyl}-7H,8H-pyrido[2,3-d]pyrimidin-7-one\u003c\/p\u003e\u003cp style=\"text-indent:-1em;padding-left:1em;\"\u003e\u003cstrong\u003eSmiles:\u003c\/strong\u003e CNC1N=C2C(C=C(C3C(Cl)=C(C=C(OC)C=3Cl)OC)C(=O)N2CCCN2CCN(CC2)C(=O)C=C)=CN=1\u003c\/p\u003e\u003cp style=\"text-indent:-1em;padding-left:1em;\"\u003e\u003cstrong\u003eInChiKey:\u003c\/strong\u003e PUIXMSRTTHLNKI-UHFFFAOYSA-N\u003c\/p\u003e\u003cp style=\"text-indent:-1em;padding-left:1em;\"\u003e\u003cstrong\u003eInChi:\u003c\/strong\u003e InChI=1S\/C26H30Cl2N6O4\/c1-5-20(35)33-11-9-32(10-12-33)7-6-8-34-24-16(15-30-26(29-2)31-24)13-17(25(34)36)21-22(27)18(37-3)14-19(38-4)23(21)28\/h5,13-15H,1,6-12H2,2-4H3,(H,29,30,31)\u003c\/p\u003e\u003cp\u003e\u003cstrong\u003eTechnical Data\u003c\/strong\u003e\u003c\/p\u003e\u003cp\u003e\u003cstrong\u003eAppearance:\u003c\/strong\u003e Solid Power\u003c\/p\u003e\u003cp\u003e\u003cstrong\u003ePurity:\u003c\/strong\u003e ≥98% (or refer to the Certificate of Analysis)\u003c\/p\u003e\u003cp style=\"text-indent:-1em;padding-left:1em;\"\u003e\u003cstrong\u003eSolubility:\u003c\/strong\u003e Solubility (25°C). 100 mg\/mL(178.1 mM). Insoluble.\u003c\/p\u003e\u003cp style=\"text-indent:-1em;padding-left:1em;\"\u003e\u003cstrong\u003eShipping Condition:\u003c\/strong\u003e Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis\u003c\/p\u003e\u003cp style=\"text-indent:-1em;padding-left:1em;\"\u003e\u003cstrong\u003eStorage Condition:\u003c\/strong\u003e Dry, dark and -20 \u003csup\u003eo\u003c\/sup\u003eC for 1 year or refer to the Certificate of Analysis.\u003c\/p\u003e\u003cp style=\"text-indent:-1em;padding-left:1em;\"\u003e\u003cstrong\u003eShelf Life:\u003c\/strong\u003e ≥12 months if stored properly.\u003c\/p\u003e\u003cp style=\"text-indent:-1em;padding-left:1em;\"\u003e\u003cstrong\u003eStock Solution Storage:\u003c\/strong\u003e 0 - 4 \u003csup\u003eo\u003c\/sup\u003eC for 1 month or refer to the Certificate of Analysis.\u003c\/p\u003e\u003cp style=\"text-indent:-1em;padding-left:1em;\"\u003e\u003cstrong\u003eDrug Formulation:\u003c\/strong\u003e To be determined\u003c\/p\u003e\u003cp\u003e\u003cstrong\u003eHS Tariff Code:\u003c\/strong\u003e 382200\u003c\/p\u003e\u003cp\u003e\u003cstrong\u003eHow to use\u003c\/strong\u003e\u003c\/p\u003e\u003cp\u003e\u003cstrong\u003eIn Vitro:\u003c\/strong\u003e\u003c\/p\u003e\u003cp style=\"padding-left:1em;\"\u003ePRN1371 is an irreversible nanomolar inhibitor of FGFR1−4. PRN1371 presents a unique profile of high biochemical and cellular potency (FGFR1 IC50 = 0.6 nM, SNU16 IC50 = 2.6 nM), prolonged target engagement (FGFR1 occupancy 24 h = 96%), \u0026lt;30% hERG inhibition at 1 μM, and good predicted ADME stability with BME reactivity Kd\u0026gt;100 μM. PRN1371 which maintained high FGFR1 occupancy with improved solubility and exceptional oral bioavailability.\u003c\/p\u003e\u003cp\u003e\u003cstrong\u003eIn Vivo:\u003c\/strong\u003e\u003c\/p\u003e\u003cp style=\"padding-left:1em;\"\u003eA rat iv (2 mg\/kg) PK study of compound 34 showed rapid clearance (Cl = 160 ml\/min\/kg), yet dosing po (20 mg\/kg) demonstrated high oral exposure (AUC = 4348 h·ng\/mL) and a reasonable half-life (t1\/2 = 3.8 h). PK studies of compound 34 in rat, dog, and cynomolgus monkey showed rapid iv clearance in all species; however there were large species differences in oral exposure and bioavailability for monkey compared to rat and dog. In rat, high exposure upon oral dosing (e.g., Cmax = 1785 ng\/mL, AUC = 4348 ng·h\/mL) and \u0026gt;100% bioavailability (F) suggested good absorption and partial saturation of clearance mechanisms at the 20 mg\/kg dose. Unique to the rat, there is a large difference in half-life between the iv (t1\/2 = 0.8 h) and po (t1\/2 = 3.8 h) routes of administration, also indicative of possible saturation of a clearance mechanism upon oral dosing. In the dogs, the same methylcellulose suspension formulation used for the rat gave low oral absorption and bioavailability (F \u0026lt; 15%). In SNU16 gastric cancer xenograft mouse model, Compound 34 induced a dose-dependent reduction in tumor volume and up to 68% tumor growth inhibition at the highest dose of 10 mg\/kg b.i.d. following 27 days of treatment. All doses were well tolerated with no significant body weight loss.\u003c\/p\u003e\u003cp\u003e\u003cstrong\u003eProducts are for research use only. Not for human use.\u003c\/strong\u003e\u003c\/p\u003e","brand":"Xcess Biosciences","offers":[{"title":"M15046-2 \/ Contact sales@xcessbio.com for quotation","offer_id":39462549913739,"sku":"","price":100.0,"currency_code":"USD","in_stock":true}],"thumbnail_url":"\/\/cdn.shopify.com\/s\/files\/1\/0389\/1897\/9723\/products\/M15046_1631108502.gif?v=1631108504","url":"https:\/\/www.xcessbio.com\/products\/m15046","provider":"Xcess Biosciences","version":"1.0","type":"link"}