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第  57 卷第  2 期                  伍 悦,等:细胞氧感受器        FIH  抑制剂的研究进展                           143

                    pyrazole HIF prolyl 4-hydroxylase inhibitors as oral erythropoi-  BO Rep, 2011, 12(5): 463-469.
                    etin  secretagogues[J].  ACS  Med  Chem  Lett,  2010,  1(9):  526-  [42]   Conejo-Garcia  A,  McDonough  MA,  Loenarz  C,  et  al.  Struc-
                    529.                                             tural basis for binding of cyclic 2-oxoglutarate analogues to fac-
               [26]   Chowdhury R, McDonough MA, Mecinović J, et al. Structural  tor-inhibiting  hypoxia-inducible  factor[J].  Bioorg  Med  Chem
                    basis  for  binding  of  hypoxia-inducible  factor  to  the  oxygen-  Lett, 2010, 20(20): 6125-6128.
                    sensing prolyl hydroxylases[J]. Structure, 2009, 17(7): 981-989.  [43]   Moon H, Han S, Park H, et al. Crystal structures of human FIH-
               [27]   Iyer SR, Chaplin VD, Knapp MJ, et al. O 2  activation by non-  1 in complex with quinol family inhibitors[J]. Mol Cells, 2010,
                         II
                    heme Fe  α-ketoglutarate-dependent enzyme variants: elucidat-  29(5): 471-474.
                    ing the role of the facial triad carboxylate in FIH[J]. J Am Chem  [44]   Hopkinson RJ, Tumber A, Yapp C, et al. 5-Carboxy-8-hydrox-
                    Soc, 2018, 140(37): 11777-11783.                 yquinoline  is  a  broad  spectrum  2-oxoglutarate oxygenase   in-
               [28]   Tarhonskaya H, Chowdhury R, Leung IKH, et al. Investigating  hibitor which causes iron translocation[J]. Chem Sci, 2013, 4(8):
                    the contribution of the active site environment to the slow reac-  3110-3117.
                    tion  of  hypoxia-inducible  factor  prolyl  hydroxylase  domain  2  [45]   McAllister  TE,  England  KS,  Hopkinson  RJ,  et  al.  Recent
                    with oxygen[J]. Biochem J, 2014, 463(3): 363-372.  progress  in  histone  demethylase  inhibitors[J].  J  Med  Chem,
               [29]   Flashman  E,  Hoffart  LM,  Hamed  RB,  et  al.  Evidence  for  the  2016, 59(4): 1308-1329.
                    slow reaction of hypoxia-inducible factor prolyl hydroxylase 2  [46]   Vachal P, Miao SW, Pierce JM, et al. 1, 3, 8-Triazaspiro [4.5]
                    with oxygen[J]. FEBS J, 2010, 277(19): 4089-4099.  decane-2, 4-diones as efficacious pan-inhibitors of hypoxia-in-
               [30]   Domene C, Jorgensen C, Schofield CJ. Mechanism of molecu-  ducible  factor  prolyl  hydroxylase  1-3  (HIF  PHD1-3)  for  the
                    lar  oxygen  diffusion  in  a  hypoxia-sensing  prolyl  hydroxylase  treatment of Anemia[J]. J Med Chem, 2012, 55(7): 2945-2959.
                    using multiscale simulation[J]. J Am Chem Soc, 2020, 142(5):  [47]   McDonough MA, McNeill LA, Tilliet M, et al. Selective inhibi-
                    2253-2263.                                       tion of factor inhibiting hypoxia-inducible factor[J]. J Am Chem
               [31]   Taabazuing  CY,  Fermann  J,  Garman  S,  et  al.  Substrate  pro-  Soc, 2005, 127(21): 7680-7681.
                    motes productive gas binding in the α-ketoglutarate-dependent  [48]   Corner TP, Teo RZR, Wu Y, et al. Structure-guided optimisa-
                    oxygenase FIH[J]. Biochemistry, 2016, 55(2): 277-286.  tion of N-hydroxythiazole-derived inhibitors of factor inhibiting
               [32]   Tarhonskaya H, Hardy AP, Howe EA, et al. Kinetic investiga-  hypoxia-inducible factor-α[J]. Chem Sci, 2023, 14(43): 12098-
                    tions  of  the  role  of  factor  inhibiting  hypoxia-inducible  factor  12120.
                    (FIH)  as  an  oxygen  sensor[J].  J  Biol  Chem,  2015,  290(32):  [49]   Martin CB, Taabazuing CY, Knapp MJ. Dynamic domain links
                    19726-19742.                                     substrate binding and catalysis in the factor-inhibiting-HIF-1[J].
               [33]   Loenarz  C,  Mecinović  J,  Chowdhury  R,  et  al.  Evidence  for  a  Biochemistry, 2023, 62(16): 2442-2449.
                    stereoelectronic  effect  in  human  oxygen  sensing[J].  Angew  [50]   Nakashima  Y,  Brewitz  L,  Tumber  A,  et  al.  2-Oxoglutarate
                    Chem Int Ed, 2009, 48(10): 1784-1787.            derivatives can selectively enhance or inhibit the activity of hu-
               [34]   Chaplin VD, Valliere MA, Hangasky JA, et al. Investigations  man oxygenases[J]. Nat Commun, 2021, 12(1): 6478.
                    on the role of a solvent tunnel in the α-ketoglutarate dependent  [51]   Wu Y, Jiang ZS, Li ZH, et al. Click chemistry-based discovery
                    oxygenase  factor  inhibiting  HIF  (FIH)[J].  J  Inorg  Biochem,  of [3-hydroxy-5-(1 H-1, 2, 3-triazol-4-yl)picolinoyl] glycines as
                    2018, 178: 63-69.                                orally  active  hypoxia-inducing factor  prolyl  hydroxylase   in-
               [35]   Hewitson KS, Liénard BMR, McDonough MA, et al. Structural  hibitors with favorable safety profiles for the treatment of Ane-
                    and  mechanistic  studies  on  the  inhibition  of  the  hypoxia-in-  mia[J]. J Med Chem, 2018, 61(12): 5332-5349.
                    ducible  transcription  factor  hydroxylases  by  tricarboxylic  acid  [52]   Li ZH, Zhen S, Su KJ, et al. A small-molecule probe for moni-
                    cycle intermediates[J]. J Biol Chem, 2007, 282(5): 3293-3301.  toring binding to prolyl hydroxylase domain 2 by fluorescence
               [36]   Yang M, Chowdhury R, Ge W, et al. Factor-inhibiting hypoxia-  polarisation[J]. Chem Commun, 2020, 56(91): 14199-14202.
                    inducible factor (FIH) catalyses the post-translational hydroxy-  [53]   Li  ZH,  Wu  Y,  Zhen  S,  et  al.  In  situ  inhibitor  synthesis  and
                    lation  of  histidinyl  residues  within  ankyrin  repeat  domains[J].  screening by fluorescence polarization: an efficient approach for
                    FEBS J, 2011, 278(7): 1086-1097.                 accelerating drug discovery[J]. Angew Chem Weinheim Bergstr
               [37]   Zhang N, Fu ZX, Linke S, et al. The asparaginyl hydroxylase  Ger, 2022, 134(45): e202211510.
                    factor  inhibiting  HIF-1alpha  is  an  essential  regulator  of  [54]   Wu Y, Chen YF, Corner TP, et al. A small-molecule inhibitor
                    metabolism[J]. Cell Metab, 2010, 11(5): 364-378.  of factor inhibiting HIF binding to a tyrosine-flip pocket for the
               [38]   Sim J, Cowburn AS, Palazon A, et al. The factor inhibiting HIF  treatment  of  obesity[J].  Angew  Chem  Int  Ed,  2024,  63(40):
                    asparaginyl hydroxylase regulates oxidative metabolism and ac-  e202410438.
                    celerates metabolic adaptation to hypoxia[J]. Cell Metab, 2018,  [55]   Wu  Y,  Zhang  ZW,  Cai  HP,  et  al.  Discovery  of  ZG-2305,  an
                    27(4): 898-913. e7.                              orally bioavailable factor inhibiting HIF inhibitor for the treat-
               [39]   Yeh TL, Leissing TM, Abboud MI, et al. Molecular and cellu-  ment of obesity and fatty liver disease[J]. J Med Chem, 2025,
                    lar mechanisms of HIF prolyl hydroxylase inhibitors in clinical  68(1): 212-235.
                    trials[J]. Chem Sci, 2017, 8(11): 7651-7668.  [56]   Hu H, Hu W, Guo AD, et al. Spatiotemporal and direct captur-
               [40]   Loenarz C, Coleman ML, Boleininger A, et al. The hypoxia-in-  ing  global  substrates  of  lysine-modifying  enzymes  in  living
                    ducible transcription factor pathway regulates oxygen sensing in  cells[J]. Nat Commun, 2024, 15(1): 1465.
                    the  simplest  animal,  Trichoplax  adhaerens[J].  EMBO  Rep,  [57]   Wu Y, Li ZH, Kaur S, et al. Light-induced, lysine-targeting irre-
                    2011, 12(1): 63-70.                              versible covalent  inhibition  of  the  human  oxygen  sensing   hy-
               [41]   Chowdhury R, Yeoh KK, Tian YM, et al. The oncometabolite  droxylase factor inhibiting HIF (FIH)[J]. J Am Chem Soc, 2025,
                    2-hydroxyglutarate inhibits histone lysine demethylases[J]. EM-  147(21): 17871-17879.
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