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Isocitrate Dehydrogenase Mutation and ( R )-2-Hydroxyglutarate: From Basic Discovery to Therapeutics Development
Open accessAbstract
The identification of heterozygous mutations in the metabolic enzyme isocitrate dehydrogenase (IDH) in subsets of cancers, including secondary glioblastoma, acute myeloid leukemia, intrahepatic cholangiocarcinoma, and chondrosarcomas, led to intense discovery efforts to delineate the mutations’ involvement in carcinogenesis and to develop therapeutics, which we review here. The three IDH isoforms (nicotinamide adenine dinucleotide phosphate–dependent IDH1 and IDH2, and nicotinamide adenine dinucleotide–dependent IDH3) contribute to regulating the circuitry of central metabolism. Several biochemical and genetic observations led to the discovery of the neomorphic production of the oncometabolite (R)-2-hydroxyglutarate (2-HG) by mutant IDH1 and IDH2 (mIDH). Heterozygous mutation of IDH1/2 and accumulation of 2-HG cause profound metabolic and epigenetic dysregulation, including inhibition of normal cellular differentiation, leading to disease. Crystallographic structural studies during the development of compounds targeting mIDH demonstrated common allosteric inhibition by distinct chemotypes. Ongoing clinical trials in patients with mIDH advanced hematologic malignancies have demonstrated compelling clinical proof-of-concept, validating the biology and drug discovery approach.
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“the concentrations at which it accumulates under pathogenic conditions suggests HIF-1α stabilisation and impaired collagen biogenesis may contribute to tumorigenicity126-130.”
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Cites
Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation
Vander Heiden, M. G., Cantley, L. C., & Thompson, C. B. (2009) · Science · doi:10.1126/science.1160809 · Cited by 16,197
Warburg, O. (1956) · Science · doi:10.1126/science.123.3191.309 · Cited by 13,425
Targeting HIF-1 for cancer therapy
Semenza, G. L. (2003) · Nature Reviews Cancer · doi:10.1038/nrc1187 · Cited by 6,717 · cited 1×
“Once translocated, HIF-1α induces expression of downstream gene targets that regulate tumor cell growth, motility, invasion, and metastasis (82).”
An Integrated Genomic Analysis of Human Glioblastoma Multiforme
Parsons, D. W., Jones, S., Zhang, X., Lin, J. C.-H., Leary, R. J., Angenendt, P., Mankoo, P., Carter, H., Siu, I.-M., Gallia, G. L., et al. (2008) · Science · doi:10.1126/science.1164382 · Cited by 5,857
IDH1 and IDH2 Mutations in Gliomas
Yan, H., Parsons, D. W., Jin, G., McLendon, R., Rasheed, B. A., Yuan, W., Kos, I., Batinic-Haberle, I., Jones, S., Riggins, G. J., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0808710 · Cited by 5,847
Conversion of 5-Methylcytosine to 5-Hydroxymethylcytosine in Mammalian DNA by MLL Partner TET1
Tahiliani, M., Koh, K. P., Shen, Y., Pastor, W. A., Bandukwala, H., Brudno, Y., Agarwal, S., Iyer, L. M., Liu, D. R., Aravind, L., et al. (2009) · Science · doi:10.1126/science.1170116 · Cited by 5,836
Genomic classification and prognosis in acute myeloid leukemia
Papaemmanuil, E., Gerstung, M., Bullinger, L., Gaidzik, V. I., Paschka, P., Roberts, N. D., Potter, N. E., Heuser, M., Thol, F., Bolli, N., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1516192 · Cited by 4,350
Cancer-associated IDH1 mutations produce 2-hydroxyglutarate
Dang, L., White, D. W., Gross, S., Bennett, B. D., Bittinger, M. A., Driggers, E. M., Fantin, V. R., Jang, H. G., Jin, S., Keenan, M. C., et al. (2009) · Nature · doi:10.1038/nature08617 · Cited by 4,154
Self-citationMetabolic Reprogramming: A Cancer Hallmark Even Warburg Did Not Anticipate
Ward, P. S., & Thompson, C. B. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.02.014 · Cited by 3,233
Xu, W., Yang, H., Liu, Y., Yang, Y., Wang, P., Kim, S.-H., Ito, S., Yang, C., Wang, P., Xiao, M.-T., et al. (2011) · Cancer Cell · doi:10.1016/j.ccr.2010.12.014 · Cited by 2,875
Figueroa, M. E., Abdel-Wahab, O., Lu, C., Ward, P. S., Patel, J., Shih, A., Li, Y., Bhagwat, N., Vasanthakumar, A., Fernandez, H. F., et al. (2010) · Cancer Cell · doi:10.1016/j.ccr.2010.11.015 · Cited by 2,766
Ito, S., D’Alessio, A. C., Taranova, O., Hong, K., Sowers, L. C., & Zhang, Y. (2010) · Nature · doi:10.1038/nature09303 · Cited by 2,628
Identification of a CpG Island Methylator Phenotype that Defines a Distinct Subgroup of Glioma
Noushmehr, H., Weisenberger, D. J., Diefes, K., Phillips, H. S., Pujara, K., Berman, B. P., Pan, F., Pelloski, C. E., Sulman, E. P., Bhat, K. P., et al. (2010) · Cancer Cell · doi:10.1016/j.ccr.2010.03.017 · Cited by 2,337
Ward, P. S., Patel, J., Wise, D. R., Abdel-Wahab, O., Bennett, B. D., Coller, H. A., Cross, J. R., Fantin, V. R., Hedvat, C. V., Perl, A. E., et al. (2010) · Cancer Cell · doi:10.1016/j.ccr.2010.01.020 · Cited by 2,020
Self-citationIDH mutation impairs histone demethylation and results in a block to cell differentiation
Lu, C., Ward, P. S., Kapoor, G. S., Rohle, D., Turcan, S., Abdel-Wahab, O., Edwards, C. R., Khanin, R., Figueroa, M. E., Melnick, A., et al. (2012) · Nature · doi:10.1038/nature10860 · Cited by 1,985
IDH1 mutation is sufficient to establish the glioma hypermethylator phenotype
Turcan, S., Rohle, D., Goenka, A., Walsh, L. A., Fang, F., Yilmaz, E., Campos, C., Fabius, A. W. M., Lu, C., Ward, P. S., et al. (2012) · Nature · doi:10.1038/nature10866 · Cited by 1,974
Reductive glutamine metabolism by IDH1 mediates lipogenesis under hypoxia
Metallo, C. M., Gameiro, P. A., Bell, E. L., Mattaini, K. R., Yang, J., Hiller, K., Jewell, C. M., Johnson, Z. R., Irvine, D. J., Guarente, L., et al. (2012) · Nature · doi:10.1038/nature10602 · Cited by 1,791
Mutation in TET2 in Myeloid Cancers
Delhommeau, F., Dupont, S., Valle, V. D., James, C., Trannoy, S., Massé, A., Kosmider, O., Le Couedic, J.-P., Robert, F., Alberdi, A., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0810069 · Cited by 1,776
Reductive carboxylation supports growth in tumour cells with defective mitochondria
Mullen, A. R., Wheaton, W. W., Jin, E. S., Chen, P.-H., Sullivan, L. B., Cheng, T., Yang, Y., Linehan, W. M., Chandel, N. S., & DeBerardinis, R. J. (2012) · Nature · doi:10.1038/nature10642 · Cited by 1,328
DNA methylation and gene silencing in cancer
Baylin, S. B. (2005) · Nature Clinical Practice Oncology · doi:10.1038/ncponc0354 · Cited by 1,176
An inhibitor of mutant IDH1 delays growth and promotes differentiation of glioma cells
Rohle, D., Popovici-Muller, J., Palaskas, N., Turcan, S., Grommes, C., Campos, C., Tsoi, J., Clark, O., Oldrini, B., Komisopoulou, E., et al. (2013) · Science · doi:10.1126/science.1236062 · Cited by 1,153
Self-citationGlioma-Derived Mutations in IDH1 Dominantly Inhibit IDH1 Catalytic Activity and Induce HIF-1α
Zhao, S., Lin, Y., Xu, W., Jiang, W., Zha, Z., Wang, P., Yu, W., Li, Z., Gong, L., Peng, Y., et al. (2009) · Science · doi:10.1126/science.1170944 · Cited by 1,119
Quantitative flux analysis reveals folate-dependent NADPH production
Fan, J., Ye, J., Kamphorst, J. J., Shlomi, T., Thompson, C. B., & Rabinowitz, J. D. (2014) · Nature · doi:10.1038/nature13236 · Cited by 1,114
Analysis of the IDH1 codon 132 mutation in brain tumors
Balss, J., Meyer, J., Mueller, W., Korshunov, A., Hartmann, C., & von Deimling, A. (2008) · Acta Neuropathologica · doi:10.1007/s00401-008-0455-2 · Cited by 1,036
The oncometabolite 2-hydroxyglutarate inhibits histone lysine demethylases
Chowdhury, R., Yeoh, K. K., Tian, Y., Hillringhaus, L., Bagg, E. A., Rose, N. R., Leung, I. K. H., Li, X. S., Woon, E. C. Y., Yang, M., et al. (2011) · The EMBO Reports · doi:10.1038/embor.2011.43 · Cited by 1,035 · cited 2×
“However, (R)-2-HG was shown to be most potent against JMJD-containing histone demethylases ( JMJD2A, JMJD2C, and FBXL11) with 50% inhibitory concentration (IC50) values of approximately 100 μM (70), suggesting that the JMJD-containing family of histone demethylases, which includes nearly 30 distinct enzymes in mammali…”
Amary, M. F., Bacsi, K., Maggiani, F., Damato, S., Halai, D., Berisha, F., Pollock, R., O'Donnell, P., Grigoriadis, A., Diss, T., et al. (2011) · The Journal of Pathology · doi:10.1002/path.2913 · Cited by 1,023
Targeted inhibition of mutant IDH2 in leukemia cells induces cellular differentiation
Wang, F., Travins, J., DeLaBarre, B., Penard-Lacronique, V., Schalm, S., Hansen, E., Straley, K., Kernytsky, A., Liu, W., Gliser, C., et al. (2013) · Science · doi:10.1126/science.1234769 · Cited by 804
Self-citationGross, S., Cairns, R. A., Minden, M. D., Driggers, E. M., Bittinger, M. A., Jang, H. G., Sasaki, M., Jin, S., Schenkein, D. P., Su, S. M., et al. (2010) · Journal of Experimental Medicine · doi:10.1084/jem.20092506 · Cited by 736
Self-citationBorger, D. R., Tanabe, K. K., Fan, K. C., Lopez, H. U., Fantin, V. R., Straley, K. S., Schenkein, D. P., Hezel, A. F., Ancukiewicz, M., Liebman, H. M., et al. (2012) · The Oncologist · doi:10.1634/theoncologist.2011-0386 · Cited by 728
Transformation by the (R)-enantiomer of 2-hydroxyglutarate linked to EGLN activation
Koivunen, P., Lee, S., Duncan, C. G., Lopez, G., Lu, G., Ramkissoon, S., Losman, J. A., Joensuu, P., Bergmann, U., Gross, S., et al. (2012) · Nature · doi:10.1038/nature10898 · Cited by 727
( R )-2-Hydroxyglutarate Is Sufficient to Promote Leukemogenesis and Its Effects Are Reversible
Losman, J.-A., Looper, R. E., Koivunen, P., Lee, S., Schneider, R. K., McMahon, C., Cowley, G. S., Root, D. E., Ebert, B. L., & Kaelin, W. G. (2013) · Science · doi:10.1126/science.1231677 · Cited by 703
Isocitrate dehydrogenase 1 and 2 mutations induce BCL-2 dependence in acute myeloid leukemia
Chan, S. M., Thomas, D., Corces, M. R., Xavy, S., Rastogi, S., Hong, W., Zhao, F., Medeiros, B. C., Tyvoll, D. A., & Majeti, R. (2015) · Nature Medicine · doi:10.1038/nm.3788 · Cited by 597
Reductive carboxylation supports redox homeostasis during anchorage-independent growth
Jiang, L., Shestov, A. A., Swain, P., Yang, C., Parker, S. J., Wang, Q. A., Terada, L. S., Adams, N. D., McCabe, M. T., Pietrak, B., et al. (2016) · Nature · doi:10.1038/nature17393 · Cited by 582
Tracing compartmentalized NADPH metabolism in the cytosol and mitochondria of mammalian cells
Lewis, C. A., Parker, S. J., Fiske, B. P., McCloskey, D., Gui, D. Y., Green, C. R., Vokes, N. I., Feist, A. M., Vander Heiden, M. G., & Metallo, C. M. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.05.008 · Cited by 562
Inhibition of Glutaminase Preferentially Slows Growth of Glioma Cells with Mutant IDH1
Seltzer, M. J., Bennett, B. D., Joshi, A. D., Gao, P., Thomas, A. G., Ferraris, D. V., Tsukamoto, T., Rojas, C. J., Slusher, B. S., Rabinowitz, J. D., et al. (2010) · Cancer Research · doi:10.1158/0008-5472.can-10-1666 · Cited by 528
Hypoxia Induces Production of L-2-Hydroxyglutarate
Intlekofer, A. M., Dematteo, R. G., Venneti, S., Finley, L. W. S., Lu, C., Judkins, A. R., Rustenburg, A. S., Grinaway, P. B., Chodera, J. D., Cross, J. R., et al. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.06.023 · Cited by 513
Breaking Cryo-EM Resolution Barriers to Facilitate Drug Discovery
Merk, A., Bartesaghi, A., Banerjee, S., Falconieri, V., Rao, P., Davis, M. I., Pragani, R., Boxer, M. B., Earl, L. A., Milne, J. L. S., et al. (2016) · Cell · doi:10.1016/j.cell.2016.05.040 · Cited by 511
Mutant IDH inhibits HNF-4α to block hepatocyte differentiation and promote biliary cancer
Saha, S. K., Parachoniak, C. A., Ghanta, K. S., Fitamant, J., Ross, K. N., Najem, M. S., Gurumurthy, S., Akbay, E. A., Sia, D., Cornellà, H., et al. (2014) · Nature · doi:10.1038/nature13441 · Cited by 460
Profiling the effects of isocitrate dehydrogenase 1 and 2 mutations on the cellular metabolome
Reitman, Z. J., Jin, G., Karoly, E. D., Spasojevic, I., Yang, J., Kinzler, K. W., He, Y., Bigner, D. D., Vogelstein, B., & Yan, H. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1019393108 · Cited by 449 · cited 1×
“In particular, expression of IDH1-R132H or IDH2-R172K mutants resulted in reduction of the TCA metabolites citrate, cis-aconitate, α-KG, malate, and fumarate, accompanied by an accumulation of biosynthetic precursors, which suggests that IDH mutation can result in TCA cycle downregulation (46).”
The ever-expanding role of HIF in tumour and stromal biology
LaGory, E. L., & Giaccia, A. J. (2016) · Nature Cell Biology · doi:10.1038/ncb3330 · Cited by 445
Structural studies on 2-oxoglutarate oxygenases and related double-stranded β-helix fold proteins
Clifton, I. J., McDonough, M. A., Ehrismann, D., Kershaw, N. J., Granatino, N., & Schofield, C. J. (2006) · Journal of Inorganic Biochemistry · doi:10.1016/j.jinorgbio.2006.01.024 · Cited by 444
Lai, A., Kharbanda, S., Pope, W. B., Tran, A. N., Solis, O. E., Peale, F. V., Jr., Forrest, W. F., Pujara, K., Carrillo, J., Pandita, A., et al. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2010.33.8715 · Cited by 440
Cytosolic NADP+-dependent isocitrate dehydrogenase status modulates oxidative damage to cells
Lee, S. M., Koh, H., Park, D., Song, B. J., Huh, T., & Park, J. (2002) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(02)00815-8 · Cited by 429
Xu, X., Zhao, J., Xu, Z., Peng, B., Huang, Q., Arnold, E., & Ding, J. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m404298200 · Cited by 407
IDH mutations in glioma and acute myeloid leukemia
Dang, L., Jin, S., & Su, S.-S. M. (2010) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2010.07.002 · Cited by 384
Self-citationIsocitrate dehydrogenase mutations in myeloid malignancies
Medeiros, B. C., Fathi, A. T., Dinardo, C. D., Pollyea, D. A., Chan, S. M., & Swords, R. T. (2016) · Leukemia · doi:10.1038/leu.2016.275 · Cited by 348
Sasaki, M., Knobbe, C. B., Itsumi, M., Elia, A. J., Harris, I. S., Chio, I. I. C., Cairns, R. A., McCracken, S., Wakeham, A., Haight, J., et al. (2012) · Genes & Development · doi:10.1101/gad.198200.112 · Cited by 296
Self-citationIsocitrate dehydrogenase mutations in gliomas
Waitkus, M. S., Diplas, B. H., & Yan, H. (2015) · Neuro-Oncology · doi:10.1093/neuonc/nov136 · Cited by 292
Progress in understanding 2‐hydroxyglutaric acidurias
Kranendijk, M., Struys, E. A., Salomons, G. S., Van der Knaap, M. S., & Jakobs, C. (2012) · Journal of Inherited Metabolic Disease · doi:10.1007/s10545-012-9462-5 · Cited by 292
Cytosolic NADP+-dependent Isocitrate Dehydrogenase Plays a Key Role in Lipid Metabolism
Koh, H., Lee, S., Son, B.-G., Lee, S.-H., Ryoo, Z. Y., Chang, K., Park, J., Park, D., Song, B. J., Veech, R. L., et al. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m402260200 · Cited by 258
Li, F., He, X., Ye, D., Lin, Y., Yu, H., Yao, C., Huang, L., Zhang, J., Wang, F., Xu, S., et al. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.10.017 · Cited by 244
Turcan, S., Fabius, A. W. M., Borodovsky, A., Pedraza, A., Brennan, C., Huse, J., Viale, A., Riggins, G. J., & Chan, T. A. (2013) · Oncotarget · doi:10.18632/oncotarget.1412 · Cited by 240
BIOSYNTHESIS OF TRICARBOXYLIC ACIDS BY CARBON DIOXIDE FIXATION
Ochoa, S. (1948) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)57383-x · Cited by 227
Mutant IDH1 promotes leukemogenesis in vivo and can be specifically targeted in human AML
Chaturvedi, A., Araujo Cruz, M. M., Jyotsana, N., Sharma, A., Yun, H., Görlich, K., Wichmann, M., Schwarzer, A., Preller, M., Thol, F., et al. (2013) · Blood · doi:10.1182/blood-2013-03-491571 · Cited by 210
Lactate dehydrogenase A silencing in IDH mutant gliomas
Chesnelong, C., Chaumeil, M. M., Blough, M. D., Al-Najjar, M., Stechishin, O. D., Chan, J. A., Pieper, R. O., Ronen, S. M., Weiss, S., Luchman, H. A., et al. (2014) · Neuro-Oncology · doi:10.1093/neuonc/not243 · Cited by 210
Human Phosphoglycerate Dehydrogenase Produces the Oncometabolite d -2-Hydroxyglutarate
Fan, J., Teng, X., Liu, L., Mattaini, K. R., Looper, R., Heiden, M. G. V., & Rabinowitz, J. D. (2014) · ACS Chemical Biology · doi:10.1021/cb500683c · Cited by 206
Sazanov, L. A., & Jackson, J. B. (1994) · FEBS Letters · doi:10.1016/0014-5793(94)00370-x · Cited by 205
Discovery of the First Potent Inhibitors of Mutant IDH1 That Lower Tumor 2-HG in Vivo
Popovici-Müller, J. V., Saunders, J. O., Salituro, F. G., Travins, J. M., Yan, S., Zhao, F., Größ, S., Dang, L., Yen, K. E., Yang, H., et al. (2012) · ACS Medicinal Chemistry Letters · doi:10.1021/ml300225h · Cited by 204
Self-citationWard, P. S., Cross, J. R., Lü, C., Weigert, O., Abdel-Wahab, O. I., Levine, R. L., Weinstock, D. M., Sharp, K. A., & Thompson, C. B. (2011) · Oncogene · doi:10.1038/onc.2011.416 · Cited by 197
IDH2 Mutations in Patients with d -2-Hydroxyglutaric Aciduria
Kranendijk, M., Struys, E. A., van Schaftingen, E., Gibson, K. M., Kanhai, W. A., van der Knaap, M. S., Amiel, J., Buist, N. R., Das, A. M., de Klerk, J. B., et al. (2010) · Science · doi:10.1126/science.1192632 · Cited by 195
New IDH1 mutant inhibitors for treatment of acute myeloid leukemia
Okoye-Okafor, U. C., Bartholdy, B., Cartier, J., Gao, E. N., Pietrak, B., Rendina, A. R., Rominger, C., Quinn, C., Smallwood, A., Wiggall, K. J., et al. (2015) · Nature Chemical Biology · doi:10.1038/nchembio.1930 · Cited by 180
Emadi, A., Jun, S. A., Tsukamoto, T., Fathi, A. T., Minden, M. D., & Dang, C. V. (2013) · Experimental Hematology · doi:10.1016/j.exphem.2013.12.001 · Cited by 167
isoCitric dehydrogenase and glutamic acid synthesis in animal tissues
Adler, E., Euler, H. V., Günther, G., & Plass, M. (1939) · Biochemical Journal · doi:10.1042/bj0331028 · Cited by 161
Hydroxyglutaric aciduria and malignant brain tumor: a case report and literature review
Aghili, M., Zahedi, F., & Rafiee, E. (2009) · Journal of Neuro-Oncology · doi:10.1007/s11060-008-9706-2 · Cited by 159
l ‐2‐Hydroxyglutaric aciduria, a defect of metabolite repair
Rzem, R., Vincent, M., SCHAFTINGEN, E. V., & Veiga‐da‐Cunha, M. (2007) · Journal of Inherited Metabolic Disease · doi:10.1007/s10545-007-0487-0 · Cited by 149
Radioprotection of IDH1 -Mutated Cancer Cells by the IDH1-Mutant Inhibitor AGI-5198
Molenaar, R. J., Botman, D., Smits, M. A., Hira, V. V., van Lith, S. A., Stap, J., Henneman, P., Khurshed, M., Lenting, K., Mul, A. N., et al. (2015) · Cancer Research · doi:10.1158/0008-5472.can-14-3603 · Cited by 148
Struys, E. A., Jansen, E. E. W., Verhoeven‐Duif, N. M., & Jakobs, C. (2004) · Clinical Chemistry · doi:10.1373/clinchem.2004.033399 · Cited by 147
Deng, G., Shen, J., Yin, M., McManus, J., Mathieu, M., Gee, P., He, T., Shi, C., Bedel, O., McLean, L. R., et al. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.608497 · Cited by 138
D‐2‐hydroxyglutaric aciduria: Case report and biochemical studies
Chalmers, R. A., Lawson, A. M., Watts, R. W. E., Tavill, A. S., Kamerling, J. P., Hey, E., & Ogilvie, D. (1980) · Journal of Inherited Metabolic Disease · doi:10.1007/bf02312516 · Cited by 135
Kölker, S., Pawlak, V., Ahlemeyer, B., Okun, J. G., Hörster, F., Mayatepek, E., Krieglstein, J., Hoffmann, G. F., & Köhr, G. (2002) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2002.02055.x · Cited by 133
Zhao, G., & Winkler, M. E. (1996) · Journal of Bacteriology · doi:10.1128/jb.178.1.232-239.1996 · Cited by 131
Quantitative metabolome analysis profiles activation of glutaminolysis in glioma with IDH1 mutation
Ohka, F., Ito, M., Ranjit, M., Senga, T., Motomura, A., Motomura, K., Saito, K., Kato, K., Kato, Y., Wakabayashi, T., et al. (2014) · Tumor Biology · doi:10.1007/s13277-014-1784-5 · Cited by 124
IDH1 Mutation Induces Reprogramming of Pyruvate Metabolism
Izquierdo-Garcia, J. L., Viswanath, P., Eriksson, P., Cai, L., Radoul, M., Chaumeil, M. M., Blough, M., Luchman, H. A., Weiss, S., Cairncross, J. G., et al. (2015) · Cancer Research · doi:10.1158/0008-5472.can-15-0840 · Cited by 123
Sugden, P. H., & Newsholme, E. A. (1975) · Biochemical Journal · doi:10.1042/bj1500105 · Cited by 113
Hominoid-specific enzyme GLUD2 promotes growth of IDH1 R132H glioma
Chen, R., Nishimura, M. C., Kharbanda, S., Peale, F., Deng, Y., Daemen, A., Forrest, W. F., Kwong, M., Hedehus, M., Hatzivassiliou, G., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1409653111 · Cited by 112
Jin, G., Reitman, Z. J., Spasojevic, I., Batinic-Haberle, I., Yang, J., Schmidt-Kittler, O., Bigner, D. D., & Yan, H. (2011) · PLoS ONE · doi:10.1371/journal.pone.0016812 · Cited by 112
A Tale of Two Subunits: How the Neomorphic R132H IDH1 Mutation Enhances Production of αHG
Pietrak, B., Zhao, H., Qi, H., Quinn, C. J., Gao, E. N., Boyer, J. G., Concha, N. O., Brown, K., Duraiswami, C., Wooster, R. F., et al. (2011) · Biochemistry · doi:10.1021/bi200499m · Cited by 112
Dalziel, K., & Londesborough, J. (1968) · Biochemical Journal · doi:10.1042/bj1100223 · Cited by 101
Hif-2α is not essential for cell-autonomous hematopoietic stem cell maintenance
Guitart, A. V., Subramani, C., Armesilla-Diaz, A., Smith, G., Sepúlveda, C., Gezer, D., Vukovic, M., Dunn, K. M., Pollard, P. J., Holyoake, T. L., et al. (2013) · Blood · doi:10.1182/blood-2013-02-484923 · Cited by 94
THE PREPARATION OF ISOCITRIC DEHYDROGENASE FROM MAMMALIAN HEART
Siebert, G., Dubuc, J., Warner, R. C., & Plaut, G. W. E. (1957) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)70882-x · Cited by 93
Davis, M. I., Größ, S., Shen, M., Straley, K. S., Pragani, R., Lea, W., Popovici-Müller, J. V., DeLaBarre, B., Artin, E., Thorne, N., et al. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.511030 · Cited by 93
Self-citationBirendra, K. C., & Dinardo, C. D. (2016) · Clinical Lymphoma Myeloma & Leukemia · doi:10.1016/j.clml.2016.04.006 · Cited by 92
Metabolic Reprogramming in Mutant IDH1 Glioma Cells
Izquierdo-García, J. L., Viswanath, P., Eriksson, P., Chaumeil, M. M., Pieper, R. O., Phillips, J. J., & Ronen, S. M. (2015) · PLoS ONE · doi:10.1371/journal.pone.0118781 · Cited by 90
Rosiers, C. D., Fernandez, C. A., David, F., & Brunengraber, H. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)46965-7 · Cited by 88
The Kinetics of Pig Heart Triphosphopyridine Nucleotide-Isocitrate Dehydrogenase
Uhr, M. L., Thompson, V. W., & Cleland, W. W. (1974) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)42719-1 · Cited by 88
Non-enzymatic chemistry enables 2-hydroxyglutarate-mediated activation of 2-oxoglutarate oxygenases
Tarhonskaya, H., Rydzik, A. M., Leung, I. K. H., Loik, N. D., Chan, M. C., Kawamura, A., McCullagh, J. S. O., Claridge, T. D. W., Flashman, E., & Schofield, C. J. (2014) · Nature Communications · doi:10.1038/ncomms4423 · Cited by 80 · cited 1×
“An alternative mechanistic explanation as to how 2-HG might enhance catalysis of EGLN2 derived from the observed nonenzymatic 2-HG conversion to α-KG, likely via iron-mediated Fenton chemistry (85).”
Wu, Y. D., & Houk, K. N. (1991) · Journal of the American Chemical Society · doi:10.1021/ja00007a002 · Cited by 77
Crystallographic Investigation and Selective Inhibition of Mutant Isocitrate Dehydrogenase
Zheng, B., Yao, Y., Liu, Z., Deng, L., Anglin, J. L., Jiang, H., Prasad, B. V. V., & Song, Y. (2013) · ACS Medicinal Chemistry Letters · doi:10.1021/ml400036z · Cited by 76
Glioma Cells with the IDH1 Mutation Modulate Metabolic Fractional Flux through Pyruvate Carboxylase
Izquierdo-García, J. L., Cai, L. M., Chaumeil, M. M., Eriksson, P., Robinson, A. E., Pieper, R. O., Phillips, J. J., & Ronen, S. M. (2014) · PLoS ONE · doi:10.1371/journal.pone.0108289 · Cited by 73
Stein, E. M., Dinardo, C. D., Altman, J. K., Collins, R. H., DeAngelo, D. J., Kantarjian, H. M., Sekeres, M. A., Fathi, A. T., Flinn, I. W., Frankel, A. E., et al. (2015) · Blood · doi:10.1182/blood.v126.23.323.323 · Cited by 72
The Kinetics of Pig Heart Triphosphopyridine Nucleotide-Isocitrate Dehydrogenase
Northrop, D. B., & Cleland, W. W. (1974) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)42720-8 · Cited by 71
Jin, Y., Elalaf, H., Watanabe, M., Tamaki, S., Hineno, S., Matsunaga, K., Woltjen, K., Kobayashi, Y., Nagata, S., Ikeya, M., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0131998 · Cited by 70
An IDH1 mutation inhibits growth of glioma cells via GSH depletion and ROS generation
Shi, J., Zuo, H., Ni, L., Xia, L., Zhao, L., Gong, M., Nie, D., Gong, P., Cui, D., Shi, W., et al. (2013) · Neurological Sciences · doi:10.1007/s10072-013-1607-2 · Cited by 67
The equilibrium constant of the isocitrate dehydrogenase reaction
Londesborough, J., & Dalziel, K. (1968) · Biochemical Journal · doi:10.1042/bj1100217 · Cited by 64
Isocitrate dehydrogenase and related oxidative decarboxylases
Dalziel, K. (1980) · FEBS Letters · doi:10.1016/0014-5793(80)80569-2 · Cited by 58
Dinardo, C. D., de Botton, S., Pollyea, D. A., Stein, E. M., Fathi, A. T., Roboz, G. J., Collins, R. H., Swords, R. T., Flinn, I. W., Altman, J. K., et al. (2015) · Blood · doi:10.1182/blood.v126.23.1306.1306 · Cited by 57
Bolli, N., Manes, N., McKerrell, T., Chi, J., Park, N., Gundem, G., Quail, M. A., Sathiaseelan, V., Herman, B., Crawley, C. R., et al. (2014) · Haematologica · doi:10.3324/haematol.2014.113381 · Cited by 54
Mitochondrial 2-hydroxyglutarate metabolism
Engqvist, M. K. M., Eßer, C., Maier, A., Lercher, M. J., & Maurino, V. G. (2014) · Mitochondrion · doi:10.1016/j.mito.2014.02.009 · Cited by 46
Struys, E. A., Verhoeven‐Duif, N. M., Brunengraber, H., & Jakobs, C. (2003) · FEBS Letters · doi:10.1016/s0014-5793(03)01459-5 · Cited by 40
IDH1, lipid metabolism and cancer: Shedding new light on old ideas
Bogdanovic, E. (2015) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2015.04.014 · Cited by 39
Grissom, C. B., & Cleland, W. W. (1988) · Biochemistry · doi:10.1021/bi00408a039 · Cited by 30
Brooks, E. E., Wu, X., Hanel, A., Nguyen, S., Wang, J., Zhang, J. H., Harrison, A., & Zhang, W. (2014) · SLAS DISCOVERY · doi:10.1177/1087057114541148 · Cited by 29
Law, J. M., Stark, S., Liu, K., Liang, N. E., Hussain, M. M., Leiendecker, M., Ito, D., Verho, O., Stern, A. M., Johnston, S. E., et al. (2016) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.6b00264 · Cited by 28
Quivoron, C., David, M., Straley, K., Travins, J., Kim, H., Chen, Y., Zhu, D., Saada, V., Bawa, O., Opolon, P., et al. (2014) · Blood · doi:10.1182/blood.v124.21.3735.3735 · Cited by 19
Wang, F., Travins, J. M., Lin, Z., Si, Y., Chen, Y., Powe, J., Murray, S., Zhu, D., Artin, E., Größ, S., et al. (2016) · Journal of Inherited Metabolic Disease · doi:10.1007/s10545-016-9960-y · Cited by 16
Self-citationWANDERS, R. J. A., DOORN, H. E. V., & Tager, J. M. (1981) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1981.tb05379.x · Cited by 14
Evidence that 2-hydroxyglutarate is not readily metabolized in colorectal carcinoma cells
Gelman, S. J., Mahieu, N. G., Cho, K., Llufrio, E. M., Wencewicz, T. A., & Patti, G. J. (2015) · Cancer & Metabolism · doi:10.1186/s40170-015-0139-z · Cited by 13
IDH1 regulates phospholipid metabolism in developing astrocytes
Bogdanovic, E., Sadri, A.-R., Catapano, M. S., Vance, J. E., & Jeschke, M. G. (2014) · Neuroscience Letters · doi:10.1016/j.neulet.2014.09.015 · Cited by 11
Drug Candidates Unveiled In Boston
Halford, B. A. (2015) · Chemical & Engineering News · doi:10.1021/cen-09338-scitech1 · Cited by 2
Research works printed but not linked: 2
- de Botton S, 2015, Haematologica, 100, 214
- Davis M, 2010, Probe Reports from the NIH Molecular Libraries Program
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Popovici-Müller, J. V., Lemieux, R. M., Artin, E., Saunders, J. O., Salituro, F. G., Travins, J. M., Cianchetta, G., Cai, Z., Zhou, D., Cui, D., et al. (2018) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.7b00421 · Cited by 457
Self-citationSynthetic lethal therapies for cancer: what’s next after PARP inhibitors?
Ashworth, A., & Lord, C. J. (2018) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-018-0055-6 · Cited by 434
Coupling Krebs cycle metabolites to signalling in immunity and cancer
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Metadata
- Authors
- Dang, L., & Su, S.-S. M.
- Affiliations
- Agios Pharmaceuticals (United States) (US)
- ORCID
- Dang, Lenny
- Venue
- Annual Review of Biochemistry
- Publisher
- Annual Reviews
- Published
- 2017-06-20
- Volume
- 86
- Issue
- 1
- Pages
- 305-331
- ISSN
- 0066-4154 (ISSN-L)
- 1545-4509
- OpenAlex
- W2556519788
- Cited by
- 204
- References
- 109
- Citations by year
- 2026: 5 · 2025: 15 · 2024: 20 · 2023: 17 · 2022: 22 · 2021: 30 · 2020: 29 · 2019: 23 · 2018: 33 · 2017: 10
- FWCI
- 2.70
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Annual Review of Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Agios Pharmaceuticals
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Health Sciences › Medicine › Oncology › Glioma Diagnosis and Treatment
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Keywords
- isocitrate dehydrogenase, IDH1 mutation, IDH2 mutation, (R)-2-hydroxyglutarate, oncometabolites, allosteric inhibition, IDH inhibitors, epigenetic dysregulation, secondary glioblastoma, acute myeloid leukemia, cholangiocarcinoma, chondrosarcoma, central carbon metabolism, hematologic malignancies, drug development
- MeSH terms
- Acetamides, Antineoplastic Agents, Benzimidazoles, Enzyme Inhibitors, Glutarates, Humans, Imidazoles, Isocitrate Dehydrogenase, Isoenzymes, Models, Molecular, Mutation, Biomarkers, Tumor, Leukemia, Myeloid, Acute, Gene Expression, Benzeneacetamides, Small Molecule Libraries, Drug Discovery, Translational Research, Biomedical
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