- Zhou, W; Wang, C; Liu, Z; Gou, S Hypoxia-Activated Prodrugs with Dual COX-2/CA Inhibitory Effects on Attenuating Cardiac Inflammation under Hypoxia. J Med Chem 65: 13436-13451 (2022)
- Wu, Y; Li, Z; McDonough, MA; Schofield, CJ; Zhang, X Inhibition of the Oxygen-Sensing Asparaginyl Hydroxylase Factor Inhibiting Hypoxia-Inducible Factor: A Potential Hypoxia Response Modulating Strategy. J Med Chem 64: 7189-7209 (2021)
- Kang, X; Long, W; Ma, C; Wang, Y; Cao, H; Wang, Y; Tan, F; Hu, Y Compounds as hypoxia mimetics, and compositions and uses thereof US Patent US8742138 (2014)
- Fu, J; Lou, Y; He, Y Indane derivatives as hypoxia inducible factor-2(α) inhibitors US Patent US12077506 (2024)
- Abdel-Magid, AF Inhibitors of Hypoxia-Inducible Factors as Treatment for Cancer. ACS Med Chem Lett 11: 1079-1080 (2020)
- Xia, Y; Choi, HK; Lee, K Recent advances in hypoxia-inducible factor (HIF)-1 inhibitors. Eur J Med Chem 49: 24-40 (2012)
- Scheuermann, TH; Stroud, D; Sleet, CE; Bayeh, L; Shokri, C; Wang, H; Caldwell, CG; Longgood, J; MacMillan, JB; Bruick, RK; Gardner, KH; Tambar, UK Isoform-Selective and Stereoselective Inhibition of Hypoxia Inducible Factor-2. J Med Chem 58: 5930-41 (2015)
- Shalwitz, R; Gardner, JH Methods for increasing the stabilization of hypoxia inducible factor-α US Patent US9278930 (2016)
- Ng, D; Arend, MP; Flippin, LA Naphthyridine derivatives as inhibitors of Hypoxia inducible factor (HIF) hydroxylase US Patent US9695170 (2017)
- Ng, D; Arend, MP; Flippin, LA Naphthyridine derivatives as inhibitors of hypoxia inducible factor (HIF) hydroxylase US Patent US8921389 (2014)
- Shimizu, K; Maruyama, M; Yasui, Y; Minegishi, H; Ban, HS; Nakamura, H Boron-containing phenoxyacetanilide derivatives as hypoxia-inducible factor (HIF)-1alpha inhibitors. Bioorg Med Chem Lett 20: 1453-6 (2010)
- Wong, WW; O'Brien-Gortner, SF; Anderson, RF; Wilson, WR; Hay, MP; Dickson, BD Hypoxia-activated prodrugs of phenolic olaparib analogues for tumour-selective chemosensitisation. RSC Med Chem 14: 1309-1330 (2023)
- Shalwitz, R; Gardner, JH Methods for increasing the stabilization of hypoxia inducible factor-1 alpha US Patent US8778412 (2014)
- Mohammed, KA; Jadulco, RC; Bugni, TS; Harper, MK; Sturdy, M; Ireland, CM Strongylophorines: natural product inhibitors of hypoxia-inducible factor-1 transcriptional pathway. J Med Chem 51: 1402-5 (2008)
- Tan, C; de Noronha, RG; Devi, NS; Jabbar, AA; Kaluz, S; Liu, Y; Mooring, SR; Nicolaou, KC; Wang, B; Van Meir, EG Sulfonamides as a new scaffold for hypoxia inducible factor pathway inhibitors. Bioorg Med Chem Lett 21: 5528-32 (2011)
- Zhu, R; Seow, HA; Baumann, RP; Ishiguro, K; Penketh, PG; Shyam, K; Sartorelli, AC Design of a hypoxia-activated prodrug inhibitor of O6-alkylguanine-DNA alkyltransferase. Bioorg Med Chem Lett 22: 6242-7 (2012)
- Chowdhury, R; Candela-Lena, JI; Chan, MC; Greenald, DJ; Yeoh, KK; Tian, YM; McDonough, MA; Tumber, A; Rose, NR; Conejo-Garcia, A; Demetriades, M; Mathavan, S; Kawamura, A; Lee, MK; van Eeden, F; Pugh, CW; Ratcliffe, PJ; Schofield, CJ Selective Small Molecule Probes for the Hypoxia Inducible Factor (HIF) Prolyl Hydroxylases. ACS Chem Biol 8: 1488-96 (2013)
- Lee, K; Lee, JH; Boovanahalli, SK; Jin, Y; Lee, M; Jin, X; Kim, JH; Hong, YS; Lee, JJ (Aryloxyacetylamino)benzoic acid analogues: A new class of hypoxia-inducible factor-1 inhibitors. J Med Chem 50: 1675-84 (2007)
- Dat, NT; Jin, X; Lee, JH; Lee, D; Hong, YS; Lee, K; Kim, YH; Lee, JJ Abietane diterpenes from Salvia miltiorrhiza inhibit the activation of hypoxia-inducible factor-1. J Nat Prod 70: 1093-7 (2007)
- Li, Z; Su, K; Jiang, Z; Yu, Y; You, Q; Zhang, X Photoactivatable Prolyl Hydroxylase 2 Inhibitors for Stabilizing the Hypoxia-Inducible Factor with Light. J Med Chem 62: 7583-7588 (2019)
- Li, Z; You, Q; Zhang, X Small-Molecule Modulators of the Hypoxia-Inducible Factor Pathway: Development and Therapeutic Applications. J Med Chem 62: 5725-5749 (2019)
- Kwon, DY; Lee, HE; Weitzel, DH; Park, K; Lee, SH; Lee, CT; Stephenson, TN; Park, H; Fitzgerald, MC; Chi, JT; Mook, RA; Dewhirst, MW; Lee, YM; Hong, J Synthesis and Biological Evaluation of Manassantin Analogues for Hypoxia-Inducible Factor 1α Inhibition. J Med Chem 58: 7659-71 (2015)
- Huang, W; Huang, R; Attene-Ramos, MS; Sakamuru, S; Englund, EE; Inglese, J; Austin, CP; Xia, M Synthesis and evaluation of quinazolin-4-ones as hypoxia-inducible factor-1a inhibitors. Bioorg Med Chem Lett 21: 5239-43 (2011)
- Mooring, SR; Jin, H; Devi, NS; Jabbar, AA; Kaluz, S; Liu, Y; Van Meir, EG; Wang, B Design and synthesis of novel small-molecule inhibitors of the hypoxia inducible factor pathway. J Med Chem 54: 8471-89 (2011)
- Minegishi, H; Fukashiro, S; Ban, HS; Nakamura, H Discovery of Indenopyrazoles as a New Class of Hypoxia Inducible Factor (HIF)-1 Inhibitors. ACS Med Chem Lett 4: 297-301 (2013)
- Fu, J; Lou, Y; He, Y Hypoxia inducible factor-2(alpha) inhibitors and their use in the treatment of diseases US Patent US11420936 (2022)
- McKee, TC; Rabe, D; Bokesch, HR; Grkovic, T; Whitson, EL; Diyabalanage, T; Van Wyk, AW; Marcum, SR; Gardella, RS; Gustafson, KR; Linehan, WM; McMahon, JB; Bottaro, DP Inhibition of hypoxia inducible factor-2 transcription: isolation of active modulators from marine sponges. J Nat Prod 75: 1632-6 (2012)
- Ghedira, D; Voissière, A; Peyrode, C; Kraiem, J; Gerard, Y; Maubert, E; Vivier, M; Miot-Noirault, E; Chezal, JM; Farhat, F; Weber, V Structure-activity relationship study of hypoxia-activated prodrugs for proteoglycan-targeted chemotherapy in chondrosarcoma. Eur J Med Chem 158: 51-67 (2018)
- Chittiboyina, AG; Kumar, GM; Carvalho, PB; Liu, Y; Zhou, YD; Nagle, DG; Avery, MA Total synthesis and absolute configuration of laurenditerpenol: a hypoxia inducible factor-1 activation inhibitor. J Med Chem 50: 6299-302 (2007)
- Li, J; Xi, W; Li, X; Sun, H; Li, Y Advances in inhibition of protein-protein interactions targeting hypoxia-inducible factor-1 for cancer therapy. Bioorg Med Chem 27: 1145-1158 (2019)
- Said, HM; Hagemann, C; Carta, F; Katzer, A; Polat, B; Staab, A; Scozzafava, A; Anacker, J; Vince, GH; Flentje, M; Supuran, CT Hypoxia induced CA9 inhibitory targeting by two different sulfonamide derivatives including acetazolamide in human glioblastoma. Bioorg Med Chem 21: 3949-57 (2013)
- Dat, NT; Jin, X; Lee, K; Hong, YS; Kim, YH; Lee, JJ Hypoxia-inducible factor-1 inhibitory benzofurans and chalcone-derived diels-alder adducts from Morus species. J Nat Prod 72: 39-43 (2009)
- Rami, M; Dubois, L; Parvathaneni, NK; Alterio, V; van Kuijk, SJ; Monti, SM; Lambin, P; De Simone, G; Supuran, CT; Winum, JY Hypoxia-targeting carbonic anhydrase IX inhibitors by a new series of nitroimidazole-sulfonamides/sulfamides/sulfamates. J Med Chem 56: 8512-20 (2013)
- Cheng, W; Yuan, Y; Qiu, N; Peng, P; Sheng, R; Hu, Y Identification of novel 4-anilinoquinazoline derivatives as potent EGFR inhibitors both under normoxia and hypoxia. Bioorg Med Chem 22: 6796-805 (2015)
- Conejo-Garcia, A; McDonough, MA; Loenarz, C; McNeill, LA; Hewitson, KS; Ge, W; Liénard, BM; Schofield, CJ; Clifton, IJ Structural basis for binding of cyclic 2-oxoglutarate analogues to factor-inhibiting hypoxia-inducible factor. Bioorg Med Chem Lett 20: 6125-8 (2010)
- Nagao, S; Yamane, Y; Funasaka, S; Tanaka, K; Miyazaki, K; Kotake, Y; Kamata, J; Watanabe-Miyano, S; Toyama, O; Ozawa, Y; Mizui, Y; Okamoto, K; Ito, D Synthesis and structure-activity relationships of novel, potent, orally active hypoxia-inducible factor-1 inhibitors. Bioorg Med Chem 22: 5513-29 (2014)
- Boovanahalli, SK; Jin, X; Jin, Y; Kim, JH; Dat, NT; Hong, YS; Lee, JH; Jung, SH; Lee, K; Lee, JJ Synthesis of (aryloxyacetylamino)-isonicotinic/nicotinic acid analogues as potent hypoxia-inducible factor (HIF)-1alpha inhibitors. Bioorg Med Chem Lett 17: 6305-10 (2007)
- De Simone, G; Vitale, RM; Di Fiore, A; Pedone, C; Scozzafava, A; Montero, JL; Winum, JY; Supuran, CT Carbonic anhydrase inhibitors: Hypoxia-activatable sulfonamides incorporating disulfide bonds that target the tumor-associated isoform IX. J Med Chem 49: 5544-51 (2006)
- Theriault, JR; Felts, AS; Bates, BS; Perez, JR; Palmer, M; Gilbert, SR; Dawson, ES; Engers, JL; Lindsley, CW; Emmitte, KA Discovery of a new molecular probe ML228: an activator of the hypoxia inducible factor (HIF) pathway. Bioorg Med Chem Lett 22: 76-81 (2011)
- Khalil, OM; Kamal, AM; Bua, S; El Sayed Teba, H; Nissan, YM; Supuran, CT Pyrrolo and pyrrolopyrimidine sulfonamides act as cytotoxic agents in hypoxia via inhibition of transmembrane carbonic anhydrases. Eur J Med Chem 188: (2020)
- Velentza, AV; Wainwright, MS; Zasadzki, M; Mirzoeva, S; Schumacher, AM; Haiech, J; Focia, PJ; Egli, M; Watterson, DM An aminopyridazine-based inhibitor of a pro-apoptotic protein kinase attenuates hypoxia-ischemia induced acute brain injury. Bioorg Med Chem Lett 13: 3465-70 (2003)
- Murray, JK; Balan, C; Allgeier, AM; Kasparian, A; Viswanadhan, V; Wilde, C; Allen, JR; Yoder, SC; Biddlecome, G; Hungate, RW; Miranda, LP Dipeptidyl-quinolone derivatives inhibit hypoxia inducible factor-1a prolyl hydroxylases-1, -2, and -3 with altered selectivity. J Comb Chem 12: 676-86 (2010)
- Discovery of DS44470011: An oral hypoxia-inducible factor prolyl hydroxylase inhibitor for the treatment of renal anemia.
- Frohn, M; Viswanadhan, V; Pickrell, AJ; Golden, JE; Muller, KM; Bürli, RW; Biddlecome, G; Yoder, SC; Rogers, N; Dao, JH; Hungate, R; Allen, JR Structure-guided design of substituted aza-benzimidazoles as potent hypoxia inducible factor-1alpha prolyl hydroxylase-2 inhibitors. Bioorg Med Chem Lett 18: 5023-6 (2008)
- Nakashima, H; Uto, Y; Nakata, E; Nagasawa, H; Ikkyu, K; Hiraoka, N; Nakashima, K; Sasaki, Y; Sugimoto, H; Shiro, Y; Hashimoto, T; Okamoto, Y; Asakawa, Y; Hori, H Synthesis and biological activity of 1-methyl-tryptophan-tirapazamine hybrids as hypoxia-targeting indoleamine 2,3-dioxygenase inhibitors. Bioorg Med Chem 16: 8661-9 (2008)
- Naik, R; Won, M; Kim, BK; Xia, Y; Choi, HK; Jin, G; Jung, Y; Kim, HM; Lee, K Synthesis and structure-activity relationship of (E)-phenoxyacrylic amide derivatives as hypoxia-inducible factor (HIF) 1a inhibitors. J Med Chem 55: 10564-71 (2012)
- Uno, M; Ban, HS; Nakamura, H 1-[4-(N-Benzylamino)phenyl]-3-phenylurea derivatives as a new class of hypoxia-inducible factor-1alpha inhibitors. Bioorg Med Chem Lett 19: 3166-9 (2009)
- Dat, NT; Jin, X; Hong, YS; Lee, JJ An isoaurone and other constituents from Trichosanthes kirilowii seeds inhibit hypoxia-inducible factor-1 and nuclear factor-kappaB. J Nat Prod 73: 1167-9 (2010)
- Kwon, HS; Kim, DR; Yang, EG; Park, YK; Ahn, HC; Min, SJ; Ahn, DR Inhibition of VEGF transcription through blockade of the hypoxia inducible factor-1α-p300 interaction by a small molecule. Bioorg Med Chem Lett 22: 5249-52 (2012)
- Naik, R; Won, M; Ban, HS; Bhattarai, D; Xu, X; Eo, Y; Hong, YS; Singh, S; Choi, Y; Ahn, HC; Lee, K Synthesis and structure-activity relationship study of chemical probes as hypoxia induced factor-1a/malate dehydrogenase 2 inhibitors. J Med Chem 57: 9522-38 (2014)
- Li, G; Shao, Y; Pan, Y; Li, Y; Wang, Y; Wang, L; Wang, X; Shao, K; Wang, S; Liu, N; Zhang, J; Zhao, W; Nakamura, H Total synthesis and biological evaluation of 7-hydroxyneolamellarin A as hypoxia-inducible factor-1α inhibitor for cancer therapy. Bioorg Med Chem Lett 50: (2021)
- Wei, H; Duan, Y; Gou, W; Cui, J; Ning, H; Li, D; Qin, Y; Liu, Q; Li, Y Design, synthesis and biological evaluation of novel 4-anilinoquinazoline derivatives as hypoxia-selective EGFR and VEGFR-2 dual inhibitors. Eur J Med Chem 181: (2019)
- Fuse, S; Ohuchi, T; Asawa, Y; Sato, S; Nakamura, H Development of 1-aryl-3-furanyl/thienyl-imidazopyridine templates for inhibitors against hypoxia inducible factor (HIF)-1 transcriptional activity. Bioorg Med Chem Lett 26: 5887-5890 (2016)
- Liu, M; Liang, Y; Zhu, Z; Wang, J; Cheng, X; Cheng, J; Xu, B; Li, R; Liu, X; Wang, Y Discovery of Novel Aryl Carboxamide Derivatives as Hypoxia-Inducible Factor 1α Signaling Inhibitors with Potent Activities of Anticancer Metastasis. J Med Chem 62: 9299-9314 (2019)
- Recent progress in the development of hypoxia-inducible factor 2α (HIF-2α) modulators: Inhibitors, agonists, and degraders (2009-2024).
- Zhou, YD; Kim, YP; Mohammed, KA; Jones, DK; Muhammad, I; Dunbar, DC; Nagle, DG Terpenoid tetrahydroisoquinoline alkaloids emetine, klugine, and isocephaeline inhibit the activation of hypoxia-inducible factor-1 in breast tumor cells. J Nat Prod 68: 947-50 (2005)
- Yasuda, Y; Arakawa, T; Nawata, Y; Shimada, S; Oishi, S; Fujii, N; Nishimura, S; Hattori, A; Kakeya, H Design, synthesis, and structure-activity relationships of 1-ethylpyrazole-3-carboxamide compounds as novel hypoxia-inducible factor (HIF)-1 inhibitors. Bioorg Med Chem 23: 1776-87 (2015)
- Liu, P; Wang, L; DuBois, BG; Colandrea, VJ; Liu, R; Cai, J; Du, X; Quan, W; Morris, W; Bai, J; Bishwokarma, B; Cheng, M; Piesvaux, J; Ray, K; Alpert, C; Chiu, CS; Zielstorff, M; Metzger, JM; Yang, L; Leung, D; Alleyne, C; Vincent, SH; Pucci, V; Li, X; Crespo, A; Stickens, D; Hale, JJ; Ujjainwalla, F; Sinz, CJ Discovery of Orally Bioavailable and Liver-Targeted Hypoxia-Inducible Factor Prolyl Hydroxylase (HIF-PHD) Inhibitors for the Treatment of Anemia. ACS Med Chem Lett 9: 1193-1198 (2018)
- Rabinowitz, MH Inhibition of hypoxia-inducible factor prolyl hydroxylase domain oxygen sensors: tricking the body into mounting orchestrated survival and repair responses. J Med Chem 56: 9369-402 (2014)
- Cai, XF; Jin, X; Lee, D; Yang, YT; Lee, K; Hong, YS; Lee, JH; Lee, JJ Phenanthroquinolizidine alkaloids from the roots of Boehmeria pannosa potently inhibit hypoxia-inducible factor-1 in AGS human gastric cancer cells. J Nat Prod 69: 1095-7 (2006)
- Fuse, S; Suzuki, K; Kuchimaru, T; Kadonosono, T; Ueda, H; Sato, S; Kizaka-Kondoh, S; Nakamura, H Design, synthesis, and evaluation of indeno[2,1-c]pyrazolones for use as inhibitors against hypoxia-inducible factor (HIF)-1 transcriptional activity. Bioorg Med Chem 28: (2020)
- Wu, CZ; Hong, SS; Cai, XF; Dat, NT; Nan, JX; Hwang, BY; Lee, JJ; Lee, D Hypoxia-inducible factor-1 and nuclear factor-kappaB inhibitory meroterpene analogues of bakuchiol, a constituent of the seeds of Psoralea corylifolia. Bioorg Med Chem Lett 18: 2619-23 (2008)
- Lee, S; Kwon, OS; Lee, CS; Won, M; Ban, HS; Ra, CS Synthesis and biological evaluation of kresoxim-methyl analogues as novel inhibitors of hypoxia-inducible factor (HIF)-1 accumulation in cancer cells. Bioorg Med Chem Lett 27: 3026-3029 (2017)
- Sakai, M; Takahashi, N; Ikeda, H; Furutani, Y; Higuchi, S; Suzuki, T; Dohmae, N; Kobayashi, S; Harada, H; Kojima, S; Matsuura, T; Hattori, A; Kakeya, H Design, synthesis, and target identification of new hypoxia-inducible factor 1 (HIF-1) inhibitors containing 1-alkyl-1H-pyrazole-3-carboxamide moiety. Bioorg Med Chem 46: (2021)
- Liu, Y; Liu, R; Mao, SC; Morgan, JB; Jekabsons, MB; Zhou, YD; Nagle, DG Molecular-targeted antitumor agents. 19. Furospongolide from a marine Lendenfeldia sp. sponge inhibits hypoxia-inducible factor-1 activation in breast tumor cells. J Nat Prod 71: 1854-60 (2008)
- An, H; Lee, S; Lee, JM; Jo, DH; Kim, J; Jeong, YS; Heo, MJ; Cho, CS; Choi, H; Seo, JH; Hwang, S; Lim, J; Kim, T; Jun, HO; Sim, J; Lim, C; Hur, J; Ahn, J; Kim, HS; Seo, SY; Na, Y; Kim, SH; Lee, J; Lee, J; Chung, SJ; Kim, YM; Kim, KW; Kim, SG; Kim, JH; Suh, YG Novel Hypoxia-Inducible Factor 1α (HIF-1α) Inhibitors for Angiogenesis-Related Ocular Diseases: Discovery of a Novel Scaffold via Ring-Truncation Strategy. J Med Chem 61: 9266-9286 (2018)
- Boccellino, M; Donniacuo, M; Bruno, F; Rinaldi, B; Quagliuolo, L; Ambruosi, M; Pace, S; De Rosa, M; Olgaç, A; Banoglu, E; Alessio, N; Massa, A; Kahn, H; Werz, O; Fiorentino, A; Filosa, R Protective effect of piceatannol and bioactive stilbene derivatives against hypoxia-induced toxicity in H9c2 cardiomyocytes and structural elucidation as 5-LOX inhibitors. Eur J Med Chem 180: 637-647 (2019)
- Wendt, B; Mulbaier, M; Wawro, S; Schultes, C; Alonso, J; Janssen, B; Lewis, J Toluidinesulfonamide hypoxia-induced factor 1 inhibitors: alleviating drug-drug interactions through use of PubChem data and comparative molecular field analysis guided synthesis. J Med Chem 54: 3982-6 (2011)
- Nocentini, A; Trallori, E; Singh, S; Lomelino, CL; Bartolucci, G; Di Cesare Mannelli, L; Ghelardini, C; McKenna, R; Gratteri, P; Supuran, CT 4-Hydroxy-3-nitro-5-ureido-benzenesulfonamides Selectively Target the Tumor-Associated Carbonic Anhydrase Isoforms IX and XII Showing Hypoxia-Enhanced Antiproliferative Profiles. J Med Chem 61: 10860-10874 (2018)
- Discovery of novel diaryl substituted isoquinolin-1(2H)-one derivatives as hypoxia-inducible factor-1 signaling inhibitors for the treatment of rheumatoid arthritis.
- Jia, T; Miao, R; Zhang, J; Zhu, H; Zhang, C; Zeng, L; Zhao, Y; Cheng, W; Shao, J Discovery of novel hypoxia-activated, nitroimidazole constructed multi-target kinase inhibitors on the basis of AZD9291 for the treatment of human lung cancer. Bioorg Med Chem 91: (2023)
- Hodges, TW; Hossain, CF; Kim, YP; Zhou, YD; Nagle, DG Molecular-targeted antitumor agents: the Saururus cernuus dineolignans manassantin B and 4-O-demethylmanassantin B are potent inhibitors of hypoxia-activated HIF-1. J Nat Prod 67: 767-71 (2004)
- Zwergel, C; Aventaggiato, M; Garbo, S; Di Bello, E; Fassari, B; Noce, B; Castiello, C; Lambona, C; Barreca, F; Rotili, D; Fioravanti, R; Schmalz, T; Weyand, M; Niedermeier, A; Tripodi, M; Colotti, G; Steegborn, C; Battistelli, C; Tafani, M; Valente, S; Mai, A Novel 1,4-Dihydropyridines as Specific Binders and Activators of SIRT3 Impair Cell Viability and Clonogenicity and Downregulate Hypoxia-Induced Targets in Cancer Cells. J Med Chem 66: 9622-9641 (2023)
- Cheng, W; Zhu, S; Ma, X; Qiu, N; Peng, P; Sheng, R; Hu, Y Design, synthesis and biological evaluation of 6-(nitroimidazole-1H-alkyloxyl)-4-anilinoquinazolines as efficient EGFR inhibitors exerting cytotoxic effects both under normoxia and hypoxia. Eur J Med Chem 89: 826-34 (2014)
- Vachal, P; Miao, S; Pierce, JM; Guiadeen, D; Colandrea, VJ; Wyvratt, MJ; Salowe, SP; Sonatore, LM; Milligan, JA; Hajdu, R; Gollapudi, A; Keohane, CA; Lingham, RB; Mandala, SM; DeMartino, JA; Tong, X; Wolff, M; Steinhuebel, D; Kieczykowski, GR; Fleitz, FJ; Chapman, K; Athanasopoulos, J; Adam, G; Akyuz, CD; Jena, DK; Lusen, JW; Meng, J; Stein, BD; Xia, L; Sherer, EC; Hale, JJ 1,3,8-Triazaspiro[4.5]decane-2,4-diones as efficacious pan-inhibitors of hypoxia-inducible factor prolyl hydroxylase 1-3 (HIF PHD1-3) for the treatment of anemia. J Med Chem 55: 2945-59 (2012)
- Vu, LP; Diehl, CJ; Casement, R; Bond, AG; Steinebach, C; Strašek, N; Bricelj, A; Perdih, A; Schnakenburg, G; Sosič, I; Ciulli, A; Gütschow, M Expanding the Structural Diversity at the Phenylene Core of Ligands for the von Hippel-Lindau E3 Ubiquitin Ligase: Development of Highly Potent Hypoxia-Inducible Factor-1α Stabilizers. J Med Chem 66: 12776-12811 (2023)
- Yu, Y; Yang, F; Yu, Q; Liu, S; Wu, C; Su, K; Yang, L; Bao, X; Li, Z; Li, X; Zhang, X Discovery of a Potent and Orally Bioavailable Hypoxia-Inducible Factor 2α (HIF-2α) Agonist and Its Synergistic Therapy with Prolyl Hydroxylase Inhibitors for the Treatment of Renal Anemia. J Med Chem 64: 17384-17402 (2021)
- Dai, J; Liu, Y; Jia, H; Zhou, YD; Nagle, DG Benzochromenones from the marine crinoid Comantheria rotula inhibit hypoxia-inducible factor-1 (HIF-1) in cell-based reporter assays and differentially suppress the growth of certain tumor cell lines. J Nat Prod 70: 1462-6 (2007)
- Dai, J; Fishback, JA; Zhou, YD; Nagle, DG Sodwanone and yardenone triterpenes from a South African species of the marine sponge Axinella inhibit hypoxia-inducible factor-1 (HIF-1) activation in both breast and prostate tumor cells. J Nat Prod 69: 1715-20 (2006)
- Mun, J; Jabbar, AA; Devi, NS; Yin, S; Wang, Y; Tan, C; Culver, D; Snyder, JP; Van Meir, EG; Goodman, MM Design and in vitro activities of N-alkyl-N-[(8-R-2,2-dimethyl-2H-chromen-6-yl)methyl]heteroarylsulfonamides, novel, small-molecule hypoxia inducible factor-1 pathway inhibitors and anticancer agents. J Med Chem 55: 6738-50 (2012)
- Wu, Y; Jiang, Z; Li, Z; Gu, J; You, Q; Zhang, X Click Chemistry-Based Discovery of [3-Hydroxy-5-(1 H-1,2,3-triazol-4-yl)picolinoyl]glycines as Orally Active Hypoxia-Inducing Factor Prolyl Hydroxylase Inhibitors with Favorable Safety Profiles for the Treatment of Anemia. J Med Chem 61: 5332-5349 (2018)
- Galdeano, C; Gadd, MS; Soares, P; Scaffidi, S; Van Molle, I; Birced, I; Hewitt, S; Dias, DM; Ciulli, A Structure-guided design and optimization of small molecules targeting the protein-protein interaction between the von Hippel-Lindau (VHL) E3 ubiquitin ligase and the hypoxia inducible factor (HIF) alpha subunit with in vitro nanomolar affinities. J Med Chem 57: 8657-63 (2014)
- Debenham, JS; Madsen-Duggan, C; Clements, MJ; Walsh, TF; Kuethe, JT; Reibarkh, M; Salowe, SP; Sonatore, LM; Hajdu, R; Milligan, JA; Visco, DM; Zhou, D; Lingham, RB; Stickens, D; DeMartino, JA; Tong, X; Wolff, M; Pang, J; Miller, RR; Sherer, EC; Hale, JJ Discovery of N-[Bis(4-methoxyphenyl)methyl]-4-hydroxy-2-(pyridazin-3-yl)pyrimidine-5-carboxamide (MK-8617), an Orally Active Pan-Inhibitor of Hypoxia-Inducible Factor Prolyl Hydroxylase 1-3 (HIF PHD1-3) for the Treatment of Anemia. J Med Chem 59: 11039-11049 (2016)
- Mun, J; Jabbar, AA; Devi, NS; Liu, Y; Van Meir, EG; Goodman, MM Structure-activity relationship of 2,2-dimethyl-2H-chromene based arylsulfonamide analogs of 3,4-dimethoxy-N-[(2,2-dimethyl-2H-chromen-6-yl)methyl]-N-phenylbenzenesulfonamide, a novel small molecule hypoxia inducible factor-1 (HIF-1) pathway inhibitor and anti-cancer agent. Bioorg Med Chem 20: 4590-7 (2012)
- Wehn, PM; Rizzi, JP; Dixon, DD; Grina, JA; Schlachter, ST; Wang, B; Xu, R; Yang, H; Du, X; Han, G; Wang, K; Cao, Z; Cheng, T; Czerwinski, RM; Goggin, BS; Huang, H; Halfmann, MM; Maddie, MA; Morton, EL; Olive, SR; Tan, H; Xie, S; Wong, T; Josey, JA; Wallace, EM Design and Activity of Specific Hypoxia-Inducible Factor-2α (HIF-2α) Inhibitors for the Treatment of Clear Cell Renal Cell Carcinoma: Discovery of Clinical Candidate ( S)-3-((2,2-Difluoro-1-hydroxy-7-(methylsulfonyl)-2,3-dihydro-1 H-inden-4-yl)oxy)-5-fluorobenzonitrile (PT2385). J Med Chem 61: 9691-9721 (2018)
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- ChEMBL_767399 (CHEMBL1825511) Inhibition of hypoxia-induced HIF1 activation in human LN229 cells expressing HRE-AP reporter gene preincubated for 1 hr under normoxia condition followed by 24 hrs incubation under hypoxia condition by HRE-luciferase reporter assay
- ChEMBL_1294789 (CHEMBL3128876) Inhibition of Stat3 phosphorylation in human OVCAR3 cells by Western blotting analysis in hypoxia condition
- ChEMBL_1294791 (CHEMBL3128878) Inhibition of Stat3 phosphorylation in human PANC1 cells by Western blotting analysis in hypoxia condition
- ChEMBL_550371 (CHEMBL999925) Inhibition of hypoxia-induced HIF1 activation in human HeLa cells by luciferase reporter gene assay
- ChEMBL_1294796 (CHEMBL3128919) Inhibition of HIF-1 alpha in human OVCAR3 cells by Western blotting analysis in hypoxia condition
- ChEMBL_1294797 (CHEMBL3128920) Inhibition of HIF-1 alpha in human PANC1 cells by Western blotting analysis in hypoxia condition
- ChEMBL_458038 (CHEMBL924307) Inhibition of hypoxia induced HIF1-alpha transcriptional activity in human Hep3B cells by reporter gene assay
- ChEMBL_458039 (CHEMBL924308) Inhibition of hypoxia induced HIF1-alpha transcriptional activity in human AGS cells by reporter gene assay
- ChEMBL_469602 (CHEMBL933161) Inhibition of hypoxia-induced HIF1 transcriptional activation in human U251-HRE cells by luciferase reporter assay
- ChEMBL_478428 (CHEMBL932617) Inhibition of hypoxia-induced HIF1 activation in human T47D cells by cell based reporter gene assay
- ChEMBL_1294792 (CHEMBL3128879) Inhibition of Stat3 phosphorylation in human MDA-MB-468 cells by Western blotting analysis in hypoxia condition
- ChEMBL_1294793 (CHEMBL3128880) Inhibition of Stat3 phosphorylation in human MDA-MB-231 cells by Western blotting analysis in hypoxia condition
- ChEMBL_2281079 Inhibition of hypoxia-induced HIF1alpha/P300 interaction (unknown origin) incubated for 30 mins for fluorescence anisotropy competition assay
- ChEMBL_428795 (CHEMBL916228) Inhibition of hypoxia induced HIF1 transcriptional activity in human Hep3B cells by cell-based HRE reporter assay
- ChEMBL_458037 (CHEMBL924306) Inhibition of hypoxia induced HIF1-alpha transcriptional activity in human Sk-Hep1 cells by reporter gene assay
- ChEMBL_573857 (CHEMBL1056199) Inhibition of hypoxia-induced HIF1 activation in human Hep3B cells by pGL3-HRE-luciferase reporter gene assay
- ChEMBL_619005 (CHEMBL1101830) Inhibition of hypoxia-induced HIF1 activation in human T47D cells by pTK-HRE3-luciferase reporter gene assay
- ChEMBL_698465 (CHEMBL1647397) Inhibition of hypoxia-induced HIF1 activation in human T47D cells by HRE3-TK-luciferase reporter gene assay
- ChEMBL_698468 (CHEMBL1647400) Inhibition of hypoxia-induced HIF1 activation in human PC3 cells by HRE3-TK-luciferase reporter gene assay
- ChEMBL_770820 (CHEMBL1837625) Inhibition of hypoxia-induced HIF1alpha activation in human ME180 cells by HRE3-Bla-luciferase reporter gene assay
- ChEMBL_881925 (CHEMBL2212528) Inhibition of HIF-1alpha in human HCT116 cells under hypoxia condition by HRE-luciferase reporter gene assay
- ChEMBL_881926 (CHEMBL2212529) Inhibition of HIF-1alpha in human LN229 cells under hypoxia condition by HRE-luciferase reporter gene assay
- ChEMBL_1294798 (CHEMBL3128921) Inhibition of HIF-1 alpha in human MDA-MB-468 cells by Western blotting analysis in hypoxia condition
- ChEMBL_1294799 (CHEMBL3128922) Inhibition of HIF-1 alpha in human MDA-MB-231 cells by Western blotting analysis in hypoxia condition
- ChEMBL_452324 (CHEMBL901549) Inhibition of hypoxia-induced HIF1 activation in human T47D cells after 16 hrs by cell based luciferase assay
- ChEMBL_550357 (CHEMBL999911) Inhibition of hypoxia-induced HIF1 activation in human T47D cells after 16 hrs by luciferase reporter gene assay
- ChEMBL_753564 (CHEMBL1799182) Inhibition of hypoxia-induced HIF1alpha activation in human Hep3B cells after 16 hrs by HRE-luciferase reporter assay
- ChEBML_1685544 Inhibition of hypoxia-induced HIF1alpha (unknown origin) transcriptional activity expressed in human HCT116 cells by HRE luciferase reporter gene assay
- ChEMBL_610892 (CHEMBL1065047) Inhibition of hypoxia-induced HIF1alpha activation in human HeLa cells after 12 hrs by HRE-luciferase reporter gene assay
- ChEMBL_1627457 (CHEMBL3869978) Inhibition of hypoxia-induced HIF1 transcriptional activity in human HeLa cells measured after 12 hrs by luciferase reporter gene assay
- ChEMBL_481732 (CHEMBL1002833) Inhibition of hypoxia-induced HIF1 activation in human T47D cells carrying pTK-HER3-luc reporter gene measured by luciferase activity
- ChEMBL_526045 (CHEMBL967263) Inhibition of hypoxia-induced HIF1 activation in human AGS cells after 16 hrs by pGL3-HRE-luciferase reporter gene assay
- ChEMBL_549581 (CHEMBL1015932) Inhibition of hypoxia-induced HIF1 activation in human T47D cells after 16 hrs by pTK-HRE3-luciferase reporter gene assay
- ChEMBL_621709 (CHEMBL1104951) Inhibition of hypoxia-induced HIF1 activation in human PC3 cells after 16 hrs by pTK-HRE3-luciferase reporter gene assay
- ChEMBL_621727 (CHEMBL1108459) Inhibition of hypoxia-induced HIF1 activation in human T47D cells after 16 hrs by pTK-HRE3-luciferase reporter gene assay
- ChEMBL_621731 (CHEMBL1108463) Inhibition of hypoxia-induced HIF1 activation in human T47D cells expressing pGL3 construct after 16 hrs by reporter gene assay
- ChEMBL_776653 (CHEMBL1913750) Inhibition of hypoxia-induced HIF1 activation in human T47D cells after 16 hrs by HRE3-TK-luciferase reporter gene assay
- ChEMBL_851302 (CHEMBL2155888) Inhibition of hypoxia-induced HIF1 activation in human T47D cells after 16 hrs by HRE3-TK-luciferase reporter gene assay
- ChEMBL_2288784 Inhibition of DHODH in human HeLa cells assessed as reduction in hypoxia-induced VEGF expression incubated for 48 hrs by ELISA assay
- ChEMBL_631037 (CHEMBL1113762) Inhibition of hypoxia-induced HIF1 activation in human T47D cells in presence of 1% O2 by HRE3-TK-luc reporter assay
- ChEMBL_2375999 Inhibition of HIF-1 alpha transcriptional activity in human U-251 cells incubated for 24 hrs under hypoxia condition by luciferse reporter assay
- ChEMBL_439940 (CHEMBL890257) Inhibition of HIF1 activation in human AGS cells assessed as inhibition of hypoxia-induced luciferase expression after 16 hrs by reporter assay
- ChEMBL_439941 (CHEMBL890258) Inhibition of HIF1 activation in human Hep3B cells assessed as inhibition of hypoxia-induced luciferase expression after 16 hrs by reporter assay
- ChEMBL_735620 (CHEMBL1693322) Inhibition of hypoxia-induced HIF1 activation in human T47D cells expressing pGL3 construct after 16 hrs by cell-based luciferase reporter assay
- ChEMBL_938618 (CHEMBL2327238) Inhibition of hypoxia-induced HIF1alpha transcriptional activity in human HeLa cells expressing HRE-Luc after 12 hrs by luciferase reporter gene assay
- Evaluation of Inhibitory Activity Against Retinal Neovascularization by Hypoxia The experiment was performed in order to evaluate inhibitory activity against angiogenesis of the compounds.
- ChEMBL_573855 (CHEMBL1055397) Inhibition of hypoxia-induced HIF1alpha protein accumulation in human Hep3B cells treated for 30 mins measured after 12 hrs by Western blot analysis
- ChEMBL_631036 (CHEMBL1113761) Inhibition of chemical hypoxia-induced HIF1 activation in human T47D cells in presence of 1, 10-phenanthrolin by HRE3-TK-luc reporter assay
- ChEMBL_636313 (CHEMBL1169036) Inhibition of hypoxia-induced HIF1alpha protein accumulation in human Hep3B cells treated for 30 mins measured after 12 hrs by Western blot analysis
- ChEMBL_1855371 (CHEMBL4356100) Inhibition of HIF1alpha transcriptional activity in hypoxia-induced human HCCLM3 cells co-transfected with luciferase reporter plasmid containing five copies of HREs and pRL-SV40 plasmid encoding Renilla luciferase incubated with compound under normoxia for 1 hr followed by hypoxia induction and measured after 24 hrs by HRE-dependent dual luciferase reporter gene assay
- ChEMBL_1891621 (CHEMBL4393448) Inhibition of hypoxia-induced HIF1alpha transcriptional activity in human Hep3B cells after 24 hrs in hypoxic condition by HRE-dependent dual luciferase reporter gene assay
- ChEMBL_1766949 (CHEMBL4202196) Inhibition of HIF-1alpha in human HRE-A549 cells pre-incubated for 1 hr before exposure to hypoxia for 24 hrs by HRE-luciferase reporter gene assay
- ChEMBL_881913 (CHEMBL2212516) Inhibition of topoisomerase-1 in human U251 cells assessed as inhibition of HIF-1-mediated hypoxia-induced VEGF expression after 24 hrs by luciferase reporter gene assay
- ChEMBL_881914 (CHEMBL2212517) Inhibition of topoisomerase-1 in human U251 cells assessed as inhibition of hypoxia-induced HIF-1alpha accumulation in nuclear extract after 6 to 24 hrs by immunoblot analysis
- ChEMBL_1465276 (CHEMBL3406495) Inhibition of HIF1 in human HT1080 cells transfected with 5xHRE/pGL3/VEGF/E1b reporter plasmid pre-incubated for 1 hr followed by incubation under hypoxia conditions for 24 hrs by HRE-driven luciferase reporter gene assay
- ChEMBL_860195 (CHEMBL2168935) Inhibition of P300 CH1 domain-mediated HIF1 transcriptional activity in human LN229-V6R cells assessed as reduction in luciferase activity incubated for 1 hr under normoxia followed by 24 hrs under hypoxia by reporter gene assay
- ChEMBL_829292 (CHEMBL2060139) Inhibition of HIF1 transcriptional activity in human LN229 cells expressing VEGF-HRE-V6R and coexpressing luciferase, lac Z gene incubated for 1 hr in normoxia condition followed by 24 hrs in hypoxia condition by reporter gene assay
- ChEMBL_2050089 (CHEMBL4704788) Inhibition of hypoxia-induced HIF1alpha transcriptional activity in human Hep3B cells co-transfected with luciferase reporter plasmid containing six copies of HREs and pRL-CMV vector assessed as reduction in luciferase activity incubated for 24 hrs under hypoxic condition by HRE-dependent dual luciferase reporter gene assay
- ChEMBL_2102766 (CHEMBL4811162) Inhibition of hypoxia-induced HIF1 alpha transcriptional activity in human HeLa cells transfected with luciferase reporter containing of HRE assessed as reduction in luciferase activity incubated for 1 hrs under normoxic condition followed by incubation under hypoxic condition for 24 hrs by luciferase reporter gene assay
- ChEMBL_2128544 (CHEMBL4837973) Inhibition of hypoxia-induced HIF1alpha transcriptional activity in human Hep3B cells co-transfected with luciferase reporter plasmid containing six copies of HREs and pRL-CMV vector assessed as reduction in luciferase activity incubated for 24 hrs under hypoxic condition by HRE-dependent dual luciferase reporter gene assay
- SAR analysis for the identification of translation initiation inhibitors (PABP) Data Source: Sanford-Burnham Center for Chemical Genomics (SBCCG) Source Affiliation: Sanford-Burnham Medical Research Institute(SBMRI, San Diego, CA) Network: NIH Molecular Libraries Probe Production Centers Network (MLPCN) Grant Number: 1R03MH084835-01 Assay Provider: Jerry Pelletier, Ph.D, McGill University, Montreal, Canada Translation is an essential cellular process whose deregulation is associated with alterations in cell growth, cell cycle progression, and cell death responses. The initiation phase of translation is a key target for regulation when cells are exposed to various environmental cues (e.g. insulin, amino acid starvation, mitogenic stimulation, hypoxia, etc). As well, translation initiation control is usurped upon viral infection and is deregulated in many human cancers. Over-expression of certain translation factors can lead to malignant transformation and many of the components of the translational apparatus are over-expressed in human cancers. Several tumor sup
- SAR analysis for the identification of translation initiation inhibitors (eIF4H) Data Source: Sanford-Burnham Center for Chemical Genomics (SBCCG) Source Affiliation: Sanford-Burnham Medical Research Institute (SBIMR, San Diego, CA) Network: NIH Molecular Libraries Probe Production Centers Network (MLPCN) Grant Number: 1R03MH084835-01 Assay Provider: Jerry Pelletier, Ph.D, McGill University, Montreal, Canada Translation is an essential cellular process whose deregulation is associated with alterations in cell growth, cell cycle progression, and cell death responses. The initiation phase of translation is a key target for regulation when cells are exposed to various environmental cues (e.g. insulin, amino acid starvation, mitogenic stimulation, hypoxia, etc). As well, translation initiation control is usurped upon viral infection and is deregulated in many human cancers. Over-expression of certain translation factors can lead to malignant transformation and many of the components of the translational apparatus are over-expressed in human cancers. Several tumor su
- uHTS fluorescence polarization assay for the identification of translation initiation inhibitors (PABP) Data Source: Sanford-Burnham Center for Chemical Genomics (SBCCG) Source Affiliation: Sanford-Burnham Medical Research Institute (SBMRI, San Diego, CA) Network: NIH Molecular Libraries Production Centers Network (MLPCN) Grant Number: 1R03MH084835-01 Assay Provider: Jerry Pelletier, Ph.D, McGill University, Montreal, Canada Translation is an essential cellular process whose deregulation is associated with alterations in cell growth, cell cycle progression, and cell death responses. The initiation phase of translation is a key target for regulation when cells are exposed to various environmental cues (e.g. insulin, amino acid starvation, mitogenic stimulation, hypoxia, etc). As well, translation initiation control is usurped upon viral infection and is deregulated in many human cancers. Over-expression of certain translation factors can lead to malignant transformation and many of the components of the translational apparatus are over-expressed in human cancers. Several tumor suppresso
- uHTS fluorescence polarization assay for the identification of translation initiation inhibitors (eIF4H) Data Source: Sanford-Burnham Center for Chemical Genomics (SBCCG) Source Affiliation: Sanford-Burnham Medical Research Institute (SBMRI, San Diego, CA) Network: NIH Molecular Libraries Production Centers Network (MLPCN) Grant Number: 1R03MH084835-01 Assay Provider: Jerry Pelletier, Ph.D, McGill University, Montreal, Canada Translation is an essential cellular process whose deregulation is associated with alterations in cell growth, cell cycle progression, and cell death responses. The initiation phase of translation is a key target for regulation when cells are exposed to various environmental cues (e.g. insulin, amino acid starvation, mitogenic stimulation, hypoxia, etc). As well, translation initiation control is usurped upon viral infection and is deregulated in many human cancers. Over-expression of certain translation factors can lead to malignant transformation and many of the components of the translational apparatus are over-expressed in human cancers. Several tumor suppresso
- Inhibitory Effect of the Compounds on PHD2 The interaction between hypoxia-inducible factor HIF-1α and VBC complex (von Hippel-Lindau protein-Elongin B-Elongin C, VBC) was detected by Fluorescence polarization (FP) method, to measure the enzyme inhibitory activity of the HIF Prolyl hydroxylases 2 (PHD2) inhibitor compounds.To a NETN (20 mM Tris.HCl, 100 mM NaCl, 1 mM EDTA, 0.5% NP-40, 1 mM PMSF) buffer containing 200 μM ascorbic acid, 20 μM α-ketoglutaric acid, 100 μM FeCl2 was added FAM-HIF (556-575) at a final concentration of 1 μM in the dark. Subsequently, the desired concentration of the test compound or the positive compound was added (the compound was replaced by the buffer in the negative control and the positive control). Finally, PHD2 was added at a final concentration of 0.5 μg/μl (PHD2 was replaced by the buffer in the negative control). They were mixed well and allowed to stand at room temperature for 30 minutes in the dark followed by 95° C. water bath for 1 minute, and then the reaction was terminated. After the temperature drops to room temperature, the sample was prepared well for use. EBC buffer (50 mM Tris.HCl, 120 mM NaCl, 0.5% NP-40) was added to the corresponding wells of a black 96-well test plate. A GST-VBC complex was added to the corresponding test wells at a final concentration of 300 nM (using the wells containing only EBC buffer as blank wells). Subsequently, the corresponding PHD2 prolyl hydroxylation reaction sample was added in the dark as a substrate with a final concentration of 100 nM. After mixing well, the lateral and longitudinal fluorescence intensity values were measured using a full-wavelength multifunctional microplate reader (TECAN infinite M1000) at an excitation wavelength of 407 nm and an emission wavelength of 518 nm.