{"product_id":"m20328","title":"PF-06650833","description":"\u003cp style=\"padding-left:1em;\"\u003ePF-06650833 is a potent, selective and orally active inhibitor of interleukin-1 receptor associated kinase 4 (IRAK4) with IC50s of 0.2 and 2.4 nM in the cell and PBMC assay, respectively. PF-06650833 is used to treat diseases such as rheumatoid arthritis, lupus, and lymphomas.\u003c\/p\u003e\u003cp\u003e\u003cstrong\u003eProduct information\u003c\/strong\u003e\u003c\/p\u003e\u003cp\u003e\u003cstrong\u003eCAS Number:\u003c\/strong\u003e 1817626-54-2\u003c\/p\u003e\u003cp\u003e\u003cstrong\u003eMolecular Weight:\u003c\/strong\u003e 361.37\u003c\/p\u003e\u003cp\u003e\u003cstrong\u003eFormula:\u003c\/strong\u003e C18H20FN3O4\u003c\/p\u003e\u003cp style=\"text-indent:-1em;padding-left:1em;\"\u003e\u003cstrong\u003eChemical Name:\u003c\/strong\u003e 1-{[(2S,3S,4S)-3-ethyl-4-fluoro-5-oxopyrrolidin-2-yl]methoxy}-7-methoxyisoquinoline-6-carboxamide\u003c\/p\u003e\u003cp style=\"text-indent:-1em;padding-left:1em;\"\u003e\u003cstrong\u003eSmiles:\u003c\/strong\u003e COC1=CC2=C(C=C1C(N)=O)C=CN=C2OC[C@H]1NC(=O)[C@@H](F)[C@H]1CC\u003c\/p\u003e\u003cp style=\"text-indent:-1em;padding-left:1em;\"\u003e\u003cstrong\u003eInChiKey:\u003c\/strong\u003e JKDGKIBAOAFRPJ-ZBINZKHDSA-N\u003c\/p\u003e\u003cp style=\"text-indent:-1em;padding-left:1em;\"\u003e\u003cstrong\u003eInChi:\u003c\/strong\u003e InChI=1S\/C18H20FN3O4\/c1-3-10-13(22-17(24)15(10)19)8-26-18-11-7-14(25-2)12(16(20)23)6-9(11)4-5-21-18\/h4-7,10,13,15H,3,8H2,1-2H3,(H2,20,23)(H,22,24)\/t10-,13+,15-\/m0\/s1\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 DMSO : ≥ 100 mg\/mL (276.72 mM).\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;\"\u003eThe kinome selectivity profile of PF-06650833 (Compound 40) is assessed in a panel of 278 kinases (Invitrogen) at 200 nM inhibitor concentration using the ATP Km for each kinase. Approximately 100% inhibition is observed for IRAK4. Lactam PF-06650833 (Compound 40) is assessed in a whole cell functional VEGF2R assay (PAE-KDR cell line). No activity is observed at concentrations up to and including 30 μM. In a voltage clamp assay, PF-06650833 inhibits hERG current by 25% at 100 μM. The ability of PF-06650833 (Compound 40) to inhibit five major CYP450 enzymes is assessed using pooled human liver microsomes and probe substrates for the CYP450 enzymes. At a concentration of 3 μM of PF-06650833, less than 5% inhibition of CYPs 1A2, 2C8, 2C9, 2D6, and 3A4 is observed. Lactam PF-06650833 is examined for time dependent inhibition effects on six major CYP450 enzymes (CYP1A2, 2B6, 2C8, 2C9, 2C19, and 2D6) using pooled human liver microsomes and probe substrates. At 100 μM of PF-06650833, no time dependent CYP inhibition is observed. The potential induction of CYP3A by PF-06650833 is assessed using cryopreserved human hepatocytes and afforded a 4.4-fold increase in mRNA at 10 μM.\u003c\/p\u003e\u003cp\u003e\u003cstrong\u003eIn Vivo:\u003c\/strong\u003e\u003c\/p\u003e\u003cp style=\"padding-left:1em;\"\u003ePF-06650833 (Compound 40; 0.3-30 mg\/kg; oral administration; for 2.5 hours; male Sprague-Dawley rats) treatment significantly inhibits LPS-induced TNF-α in a dose dependent manner. Mean exposures of PF-06650833 in plasma are 2.1 nM, 7.7 nM, 19 nM and 150 nM free, respectively, at 2.5 hours after oral administration of PF-06650833 at 0.3, 1, 3, and 30 mg\/kg. The fraction unbound in rat plasma of PF-06650833 is 0.3.\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":"M20328-C \/ Contact sales@xcessbio.com for quotation","offer_id":39524232659083,"sku":"0","price":100.0,"currency_code":"USD","in_stock":false}],"thumbnail_url":"\/\/cdn.shopify.com\/s\/files\/1\/0389\/1897\/9723\/products\/M20328_1635198587.gif?v=1635198588","url":"https:\/\/www.xcessbio.com\/products\/m20328","provider":"Xcess Biosciences","version":"1.0","type":"link"}