PF-06835919

• CAS: 2102501-84-6
• Catalog Number: ACM2102501846
• Category: Inhibitors
• Molecular Weight: 356.35
• Molecular Formula: C16H19F3N4O2
• Description: PF-06835919, also known as MDK1846, is a potent ketohexokinase (KHK) inhibitor. PF-06835919 is reported in patent US 20170183328 A1, example 4. Increased fructose consumption and its subsequent metabolism have been implicated in hepatic steatosis, dyslipidemia, obesity, and insulin resistance in humans. Since ketohexokinase (KHK) is the principal enzyme responsible for fructose metabolism, identification of a selective KHK inhibitor may help to further elucidate the effect of KHK inhibition on these metabolic disorders.
• Synonyms: PF-06835919; PF 06835919; PF06835919; MDK1846; MDK-1846; MDK 1846; ketohexokinase inhibitor; ketohexokinase-In-1
• IUPAC Name: 2-((1R,5S,6R)-3-(2-((S)-2-methylazetidin-1-yl)-6-(trifluoromethyl)pyrimidin-4-yl)-3-azabicyclo[3.1.0]hexan-6-yl)acetic acid
• Canonical SMILES: O=C(C[C@@H]1[C@]2(CN(C[C@@]12[H])C3=NC(N4[C@H](CC4)C)=NC(C(F)(F)F)=C3)[H])O
• InChI: InChI=1S/C16H19F3N4O2/c1-8-2-3-23(8)15-20-12(16(17,18)19)5-13(21-15)22-6-10-9(4-14(24)25)11(10)7-22/h5,8-11H,2-4,6-7H2,1H3,(H,24,25)/t8-,9-,10-,11+/m0/s1
• InChI Key: MDUYWDNWFXSMJJ-XWLWVQCSSA-N
• Solubility: Soluble in DMSO
• Appearance: Solid powder
• Shelf Life: >2 years if stored properly
• Storage: Dry, dark and at 0-4 °C for short term (days to weeks) or -20 °C for long term (months to years).
• Biological Target: Ketohexokinase inhibitor 1 is an inhibitor of ketohexokinase (KHK), with IC50s of 8.4 nM and 66 nM for KHK-C and KHK-A, respectively.
• Drug Formulation: This drug may be formulated in DMSO
• Elemental Analysis: C, 53.93; H, 5.37; F, 15.99; N, 15.72; O, 8.98
• Exact Mass: 356.146
• HS Tariff Code: 2934.99.9001
• In Vitro Activity: PF-06835919 showed active uptake in cultured primary human hepatocytes, and substrate activity to organic anion transporter (OAT)2 and organic anion transporting-polypeptide (OATP)1B1 in transfected cells. PF-06835919 showed low intrinsic metabolic clearance in vitro, and was found to be metabolized via both oxidative pathways (58%) and acyl glucuronidation (42%) by CYP3A, CYP2C8, CYP2C9 and UGT2B7.; Reference: Drug Metab Dispos. 2022 Jul 2:DMD-AR-2022-000953. https://pubmed.ncbi.nlm.nih.gov/35779864/
• In Vivo Activity: Compared with placebo, significant reductions in WLF were observed in participants receiving PF-06835919 300 mg (difference of -18.73%; p = 0.04), but not with 75 mg. In addition, inhibition of KHK resulted in improvement in inflammatory markers. The incidence of treatment-emergent adverse events (AEs) was low and similar across treatment groups (26.3%, 23.5%, and 29.4% of participants in the placebo and PF-06835919 75 mg and 300 mg groups, respectively).; Reference: Med (N Y). 2021 Jul 9;2(7):800-813.e3. https://pubmed.ncbi.nlm.nih.gov/35590219/
• Shipping: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
• Stock Solution Storage: 0-4 °C for short term (days to weeks), or -20 °C for long term (months).