Indoximod (BioDeep_00000782983)
代谢物信息卡片
Indoximod
化学式: C12H14N2O2 (218.1055224)
中文名称: 吲哚莫德
谱图信息:
最多检出来源 () 0%
分子结构信息
SMILES: CN1C=C(C2=CC=CC=C21)CC(C(=O)O)N
InChI: InChI=1S/C12H14N2O2/c1-14-7-8(6-10(13)12(15)16)9-4-2-3-5-11(9)14/h2-5,7,10H,6,13H2,1H3,(H,15,16)/t10-/m1/s1
描述信息
C308 - Immunotherapeutic Agent > C129820 - Antineoplastic Immunomodulating Agent
C308 - Immunotherapeutic Agent > C141144 - Immune Checkpoint Modulator
C471 - Enzyme Inhibitor > C141137 - IDO1 Inhibitor
C274 - Antineoplastic Agent
同义名列表
1 个代谢物同义名
数据库引用编号
5 个数据库交叉引用编号
- KEGGdrug: D10640
- PubChem: 405012
- DrugBank: DB12827
- ChEMBL: CHEMBL571209
- CAS: 110117-83-4
分类词条
相关代谢途径
Reactome(0)
BioCyc(0)
PlantCyc(0)
代谢反应
0 个相关的代谢反应过程信息。
Reactome(0)
BioCyc(0)
WikiPathways(0)
Plant Reactome(0)
INOH(0)
PlantCyc(0)
COVID-19 Disease Map(0)
PathBank(0)
PharmGKB(0)
0 个相关的物种来源信息
在这里通过桑基图来展示出与当前的这个代谢物在我们的BioDeep知识库中具有相关联信息的其他代谢物。在这里进行关联的信息来源主要有：
- PubMed: 来源于PubMed文献库中的文献信息，我们通过自然语言数据挖掘得到的在同一篇文献中被同时提及的相关代谢物列表，这个列表按照代谢物同时出现的文献数量降序排序，取前10个代谢物作为相关研究中关联性很高的代谢物集合展示在桑基图中。
- NCBI Taxonomy: 通过文献数据挖掘，得到的代谢物物种来源信息关联。这个关联信息同样按照出现的次数降序排序，取前10个代谢物作为高关联度的代谢物集合展示在桑吉图上。
- Chemical Taxonomy: 在物质分类上处于同一个分类集合中的其他代谢物
- Chemical Reaction: 在化学反应过程中，存在为当前代谢物相关联的生化反应过程中的反应底物或者反应产物的关联代谢物信息。
点击图上的相关代谢物的名称，可以跳转到相关代谢物的信息页面。
文献列表
- Cui Huo, Zongyuan Luo, Xiangli Ning, Xin Kang, Qin Yan, Yuying Guo, Guobo Li, Zhouyu Wang, Yuzhi Li, Shan Qian. 4,6-Disubstituted-1H-Indazole-4-Amine derivatives with immune-chemotherapy effect and in vivo antitumor activity.
European journal of medicinal chemistry.
2022 Nov; 241(?):114625. doi:
10.1016/j.ejmech.2022.114625. [PMID: 35952399] - Xiang-Li Ning, Yu-Zhi Li, Cui Huo, Ji Deng, Cheng Gao, Kai-Rong Zhu, Miao Wang, Yu-Xiang Wu, Jun-Lin Yu, Ya-Li Ren, Zong-Yuan Luo, Gen Li, Yang Chen, Si-Yao Wang, Cheng Peng, Ling-Ling Yang, Zhou-Yu Wang, Yong Wu, Shan Qian, Guo-Bo Li. X-ray Structure-Guided Discovery of a Potent, Orally Bioavailable, Dual Human Indoleamine/Tryptophan 2,3-Dioxygenase (hIDO/hTDO) Inhibitor That Shows Activity in a Mouse Model of Parkinson's Disease.
Journal of medicinal chemistry.
2021 06; 64(12):8303-8332. doi:
10.1021/acs.jmedchem.1c00303. [PMID: 34110158] - Qi Su, Changrong Wang, Huijuan Song, Chuangnian Zhang, Jinjian Liu, Pingsheng Huang, Yumin Zhang, Jianhuan Zhang, Weiwei Wang. Co-delivery of anionic epitope/CpG vaccine and IDO inhibitor by self-assembled cationic liposomes for combination melanoma immunotherapy.
Journal of materials chemistry. B.
2021 05; 9(18):3892-3899. doi:
10.1039/d1tb00256b. [PMID: 33928989] - Diana Čepcová, Ido P Kema, Maria Sandovici, Leo E Deelman, Katarína Šišková, Ján Klimas, Peter Vavrinec, Diana Vavrincová-Yaghi. The protective effect of 1-methyltryptophan isomers in renal ischemia-reperfusion injury is not exclusively dependent on indolamine 2,3-dioxygenase inhibition.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.
2021 Mar; 135(?):111180. doi:
10.1016/j.biopha.2020.111180. [PMID: 33433354] - Eugenio Llorens, Loredana Scalschi, Ana I González-Hernández, Gemma Camañes, Pilar García-Agustín, Begonya Vicedo. 1-Methyltryptophan Treatment Increases Defense-Related Proteins in the Apoplast of Tomato Plants.
Journal of proteome research.
2021 01; 20(1):433-443. doi:
10.1021/acs.jproteome.0c00498. [PMID: 32989989] - Kuo-Ching Mei, Yu-Pei Liao, Jinhong Jiang, Michelle Chiang, Mercedeh Khazaieli, Xiangsheng Liu, Xiang Wang, Qi Liu, Chong Hyun Chang, Xiao Zhang, Juan Li, Ying Ji, Brenda Melano, Donatello Telesca, Tian Xia, Huan Meng, Andre E Nel. Liposomal Delivery of Mitoxantrone and a Cholesteryl Indoximod Prodrug Provides Effective Chemo-immunotherapy in Multiple Solid Tumors.
ACS nano.
2020 10; 14(10):13343-13366. doi:
10.1021/acsnano.0c05194. [PMID: 32940463] - Huihan Ma, Qian Qin, Jiaqing Mi, Qinmei Feng. 1-MT inhibits the invasion of CBP-resistant ovarian cancer cells via down-regulating IDO expression and re-activating immune cells function.
BMC pharmacology & toxicology.
2020 09; 21(1):67. doi:
10.1186/s40360-020-00439-w. [PMID: 32912307] - Sanjeev Kumar, Firoz A Jaipuri, Jesse P Waldo, Hima Potturi, Agnieszka Marcinowicz, James Adams, Clarissa Van Allen, Hong Zhuang, Nicholas Vahanian, Charles Link, Erik L Brincks, Mario R Mautino. Discovery of indoximod prodrugs and characterization of clinical candidate NLG802.
European journal of medicinal chemistry.
2020 Jul; 198(?):112373. doi:
10.1016/j.ejmech.2020.112373. [PMID: 32422549] - Wei Du, Chen Chen, Peng Sun, Shengchang Zhang, Jing Zhang, Xiaoyu Zhang, Ying Liu, Rui Zhang, Chongzheng Yan, Changchun Fan, Jibiao Wu, Xinyi Jiang. Eliciting an immune hot tumor niche with biomimetic drug-based multi-functional nanohybrids augments immune checkpoint blockade-based breast cancer therapy.
Nanoscale.
2020 Feb; 12(5):3317-3329. doi:
10.1039/c9nr09835f. [PMID: 31976511] - Elisa Wirthgen, Anne K Leonard, Christian Scharf, Grazyna Domanska. The Immunomodulator 1-Methyltryptophan Drives Tryptophan Catabolism Toward the Kynurenic Acid Branch.
Frontiers in immunology.
2020; 11(?):313. doi:
10.3389/fimmu.2020.00313. [PMID: 32180772] - Jonatan Ahlstedt, Elise Konradsson, Crister Ceberg, Henrietta Nittby Redebrandt. Increased effect of two-fraction radiotherapy in conjunction with IDO1 inhibition in experimental glioblastoma.
PloS one.
2020; 15(5):e0233617. doi:
10.1371/journal.pone.0233617. [PMID: 32469935] - Elisa Wirthgen, Winfried Otten, Margret Tuchscherer, Armin Tuchscherer, Grazyna Domanska, Julia Brenmoehl, Juliane Günther, Daniela Ohde, Werner Weitschies, Anne Seidlitz, Eberhard Scheuch, Ellen Kanitz. Effects of 1-Methyltryptophan on Immune Responses and the Kynurenine Pathway after Lipopolysaccharide Challenge in Pigs.
International journal of molecular sciences.
2018 Oct; 19(10):. doi:
10.3390/ijms19103009. [PMID: 30279361] - Sudeep Chenna Narendra, Jaya Prakash Chalise, Sophie Biggs, Ulrich Kalinke, Mattias Magnusson. Regulatory T-Cells Mediate IFN-α-Induced Resistance against Antigen-Induced Arthritis.
Frontiers in immunology.
2018; 9(?):285. doi:
10.3389/fimmu.2018.00285. [PMID: 29515584] - P Calleja, J M Irache, C Zandueta, C Martínez-Oharriz, S Espuelas. A combination of nanosystems for the delivery of cancer chemoimmunotherapeutic combinations: 1-Methyltryptophan nanocrystals and paclitaxel nanoparticles.
Pharmacological research.
2017 Dec; 126(?):77-83. doi:
10.1016/j.phrs.2017.09.004. [PMID: 28893628] - Jianqin Lu, Xiangsheng Liu, Yu-Pei Liao, Felix Salazar, Bingbing Sun, Wen Jiang, Chong Hyun Chang, Jinhong Jiang, Xiang Wang, Anna M Wu, Huan Meng, Andre E Nel. Nano-enabled pancreas cancer immunotherapy using immunogenic cell death and reversing immunosuppression.
Nature communications.
2017 11; 8(1):1811. doi:
10.1038/s41467-017-01651-9. [PMID: 29180759] - Luiz Henrique Gomes Matheus, Gislene Mendes Simão, Taíssa Altieri Amaral, Rodrigo Barbosa Oliveira Brito, Camila Soares Malta, Yves Silva Teles Matos, Alexandre Chagas Santana, Gabriela Gomes Cardoso Rodrigues, Maria Clara Albejante, Erna Elisabeth Bach, Maria Aparecida Dalboni, Cleber Pinto Camacho, Humberto Dellê. Indoleamine 2, 3-dioxygenase (IDO) increases during renal fibrogenesis and its inhibition potentiates TGF-β 1-induced epithelial to mesenchymal transition.
BMC nephrology.
2017 Sep; 18(1):287. doi:
10.1186/s12882-017-0702-7. [PMID: 28877670] - Tatiane da Silva Araújo, Adriano Jose Maia Chaves Filho, Aline Santos Monte, Ana Isabelle de Góis Queiroz, Rafaela Carneiro Cordeiro, Michel de Jesus Souza Machado, Ricardo de Freitas Lima, David Freitas de Lucena, Michael Maes, Danielle Macêdo. Reversal of schizophrenia-like symptoms and immune alterations in mice by immunomodulatory drugs.
Journal of psychiatric research.
2017 01; 84(?):49-58. doi:
10.1016/j.jpsychires.2016.09.017. [PMID: 27697587] - Elisa Wirthgen, Ellen Kanitz, Margret Tuchscherer, Armin Tuchscherer, Grazyna Domanska, Werner Weitschies, Anne Seidlitz, Eberhard Scheuch, Winfried Otten. Pharmacokinetics of 1-methyl-L-tryptophan after single and repeated subcutaneous application in a porcine model.
Experimental animals.
2016 May; 65(2):147-55. doi:
10.1538/expanim.15-0096. [PMID: 26725587] - Hatem H Soliman, Susan E Minton, Hyo Sook Han, Roohi Ismail-Khan, Anthony Neuger, Fatema Khambati, David Noyes, Richard Lush, Alberto A Chiappori, John D Roberts, Charles Link, Nicholas N Vahanian, Mario Mautino, Howard Streicher, Daniel M Sullivan, Scott J Antonia. A phase I study of indoximod in patients with advanced malignancies.
Oncotarget.
2016 Apr; 7(16):22928-38. doi:
10.18632/oncotarget.8216. [PMID: 27008709] - Lin Xie, Jun Maeda, Katsushi Kumata, Joji Yui, Yiding Zhang, Akiko Hatori, Nobuki Nengaki, Hidekatsu Wakizaka, Masayuki Fujinaga, Tomoteru Yamasaki, Yoko Shimoda, Makoto Higuchi, Tetsuya Suhara, Feng Wang, Ming-Rong Zhang. Development of 1-N-(11)C-Methyl-L- and -D-Tryptophan for pharmacokinetic imaging of the immune checkpoint inhibitor 1-Methyl-Tryptophan.
Scientific reports.
2015 Nov; 5(?):16417. doi:
10.1038/srep16417. [PMID: 26552594] - Gemma Camañes, Loredana Scalschi, Begonya Vicedo, Carmen González-Bosch, Pilar García-Agustín. An untargeted global metabolomic analysis reveals the biochemical changes underlying basal resistance and priming in Solanum lycopersicum, and identifies 1-methyltryptophan as a metabolite involved in plant responses to Botrytis cinerea and Pseudomonas syringae.
The Plant journal : for cell and molecular biology.
2015 Oct; 84(1):125-39. doi:
10.1111/tpj.12964. [PMID: 26270176] - Nobuhiko Nakamura, Takeshi Hara, Masahito Shimizu, Ryoko Mabuchi, Junji Nagano, Tomohiko Ohno, Takahiro Kochi, Masaya Kubota, Yohei Shirakami, Naoe Goto, Hiroyasu Ito, Kuniaki Saito, Takuji Tanaka, Hisataka Moriwaki, Hisashi Tsurumi. Effects of indoleamine 2,3-dioxygenase inhibitor in non-Hodgkin lymphoma model mice.
International journal of hematology.
2015 Sep; 102(3):327-34. doi:
10.1007/s12185-015-1835-8. [PMID: 26243621] - S Schulz, A Landi, R Garg, J A Wilson, S van Drunen Littel-van den Hurk. Indolamine 2,3-dioxygenase expression by monocytes and dendritic cell populations in hepatitis C patients.
Clinical and experimental immunology.
2015 Jun; 180(3):484-98. doi:
10.1111/cei.12586. [PMID: 25605587] - M W H J Demmers, S S Korevaar, M Roemeling-van Rhijn, T P P van den Bosch, M J Hoogduijn, M G H Betjes, W Weimar, C C Baan, A T Rowshani. Human renal tubular epithelial cells suppress alloreactive T cell proliferation.
Clinical and experimental immunology.
2015 Mar; 179(3):509-19. doi:
10.1111/cei.12469. [PMID: 25310899] - Yu-Ning Liu, Yun-Li Peng, Lei -Liu, Teng-Yun Wu, Yi Zhang, Yong-Jie Lian, Yuan-Yuan Yang, Keith W Kelley, Chun-Lei Jiang, Yun-Xia Wang. TNFα mediates stress-induced depression by upregulating indoleamine 2,3-dioxygenase in a mouse model of unpredictable chronic mild stress.
European cytokine network.
2015 Jan; 26(1):15-25. doi:
10.1684/ecn.2015.0362. [PMID: 26083579] - Anle Zhang, Yuanhong Zheng, Zujun Que, Lingling Zhang, Shengchao Lin, Vanminh Le, Jianwen Liu, Jianhui Tian. Astragaloside IV inhibits progression of lung cancer by mediating immune function of Tregs and CTLs by interfering with IDO.
Journal of cancer research and clinical oncology.
2014 Nov; 140(11):1883-90. doi:
10.1007/s00432-014-1744-x. [PMID: 24980548] - Ji-Young Lim, Sung-Eun Lee, Gyenogsin Park, Eun Young Choi, Chang-Ki Min. Inhibition of indoleamine 2,3-dioxygenase by stereoisomers of 1-methyl tryptophan in an experimental graft-versus-tumor model.
Experimental hematology.
2014 Oct; 42(10):862-6.e3. doi:
10.1016/j.exphem.2014.06.006. [PMID: 24971697] - Hatem H Soliman, Erica Jackson, Tony Neuger, E Claire Dees, R Donald Harvey, Hyo Han, Roohi Ismail-Khan, Susan Minton, Nicholas N Vahanian, Charles Link, Daniel M Sullivan, Scott Antonia. A first in man phase I trial of the oral immunomodulator, indoximod, combined with docetaxel in patients with metastatic solid tumors.
Oncotarget.
2014 Sep; 5(18):8136-46. doi:
10.18632/oncotarget.2357. [PMID: 25327557] - Richard Metz, Courtney Smith, James B DuHadaway, Phillip Chandler, Babak Baban, Lauren M F Merlo, Elizabeth Pigott, Martin P Keough, Sonja Rust, Andrew L Mellor, Laura Mandik-Nayak, Alexander J Muller, George C Prendergast. IDO2 is critical for IDO1-mediated T-cell regulation and exerts a non-redundant function in inflammation.
International immunology.
2014 Jul; 26(7):357-67. doi:
10.1093/intimm/dxt073. [PMID: 24402311] - Wei Xie, Lun Cai, Yunhong Yu, Liang Gao, Limin Xiao, Qianchao He, Zhijun Ren, Yuanzheng Liu. Activation of brain indoleamine 2,3-dioxygenase contributes to epilepsy-associated depressive-like behavior in rats with chronic temporal lobe epilepsy.
Journal of neuroinflammation.
2014 Mar; 11(?):41. doi:
10.1186/1742-2094-11-41. [PMID: 24594021] - Marcus A Lawson, Jennifer M Parrott, Robert H McCusker, Robert Dantzer, Keith W Kelley, Jason C O'Connor. Intracerebroventricular administration of lipopolysaccharide induces indoleamine-2,3-dioxygenase-dependent depression-like behaviors.
Journal of neuroinflammation.
2013 Jul; 10(?):87. doi:
10.1186/1742-2094-10-87. [PMID: 23866724] - Sergio Rutella, Franco Locatelli. Targeting multiple-myeloma-induced immune dysfunction to improve immunotherapy outcomes.
Clinical & developmental immunology.
2012; 2012(?):196063. doi:
10.1155/2012/196063. [PMID: 22567028] - Qing-Feng Sun, Ji-Guang Ding, Ji-Fang Sheng, Man-Hua Zhu, Jun-Jie Li, Zi-Ke Sheng, Xiao-Feng Tang. Novel action of 3,4-DAA ameliorating acute liver allograft injury.
Cell biochemistry and function.
2011 Dec; 29(8):673-8. doi:
10.1002/cbf.1805. [PMID: 21932299] - Katherine A Jackman, Vanessa H Brait, Yutang Wang, Ghassan J Maghzal, Helen J Ball, Gavin McKenzie, T Michael De Silva, Roland Stocker, Christopher G Sobey. Vascular expression, activity and function of indoleamine 2,3-dioxygenase-1 following cerebral ischaemia-reperfusion in mice.
Naunyn-Schmiedeberg's archives of pharmacology.
2011 May; 383(5):471-81. doi:
10.1007/s00210-011-0611-4. [PMID: 21359968] - T Eleftheriadis, T Sparopoulou, G Antoniadi, V Liakopoulos, I Stefanidis, G Galaktidou. Suppression of humoral immune response to hepatitis B surface antigen vaccine in BALB/c mice by 1-methyl-tryptophan co-administration.
Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences.
2011; 19(3):236-9. doi:
NULL. [PMID: 22615663] - Zhidan Tu, Qing Li, Hong Bu, Feng Lin. Mesenchymal stem cells inhibit complement activation by secreting factor H.
Stem cells and development.
2010 Nov; 19(11):1803-9. doi:
10.1089/scd.2009.0418. [PMID: 20163251] - Cornelia Kiank, Jan-Philip Zeden, Solveig Drude, Grazyna Domanska, Gerhard Fusch, Winfried Otten, Christine Schuett. Psychological stress-induced, IDO1-dependent tryptophan catabolism: implications on immunosuppression in mice and humans.
PloS one.
2010 Jul; 5(7):e11825. doi:
10.1371/journal.pone.0011825. [PMID: 20689575] - Feng Qian, Jeannine Villella, Paul K Wallace, Paulette Mhawech-Fauceglia, Joseph D Tario, Christopher Andrews, Junko Matsuzaki, Danila Valmori, Maha Ayyoub, Peter J Frederick, Amy Beck, Jianqun Liao, Richard Cheney, Kirsten Moysich, Shashikant Lele, Protul Shrikant, Lloyd J Old, Kunle Odunsi. Efficacy of levo-1-methyl tryptophan and dextro-1-methyl tryptophan in reversing indoleamine-2,3-dioxygenase-mediated arrest of T-cell proliferation in human epithelial ovarian cancer.
Cancer research.
2009 Jul; 69(13):5498-504. doi:
10.1158/0008-5472.can-08-2106. [PMID: 19491279] - J C O'Connor, M A Lawson, C André, M Moreau, J Lestage, N Castanon, K W Kelley, R Dantzer. Lipopolysaccharide-induced depressive-like behavior is mediated by indoleamine 2,3-dioxygenase activation in mice.
Molecular psychiatry.
2009 May; 14(5):511-22. doi:
10.1038/sj.mp.4002148. [PMID: 18195714] - Adriano Boasso, Monica Vaccari, Dietmar Fuchs, Andrew W Hardy, Wen-Po Tsai, Elzbieta Tryniszewska, Gene M Shearer, Genoveffa Franchini. Combined effect of antiretroviral therapy and blockade of IDO in SIV-infected rhesus macaques.
Journal of immunology (Baltimore, Md. : 1950).
2009 Apr; 182(7):4313-20. doi:
10.4049/jimmunol.0803314. [PMID: 19299731] - Helen J Ball, Hajime J Yuasa, Christopher J D Austin, Silvia Weiser, Nicholas H Hunt. Indoleamine 2,3-dioxygenase-2; a new enzyme in the kynurenine pathway.
The international journal of biochemistry & cell biology.
2009 Mar; 41(3):467-71. doi:
10.1016/j.biocel.2008.01.005. [PMID: 18282734] - Wei Chen, Xueqing Liang, Amanda J Peterson, David H Munn, Bruce R Blazar. The indoleamine 2,3-dioxygenase pathway is essential for human plasmacytoid dendritic cell-induced adaptive T regulatory cell generation.
Journal of immunology (Baltimore, Md. : 1950).
2008 Oct; 181(8):5396-404. doi:
10.4049/jimmunol.181.8.5396. [PMID: 18832696] - Senthil Karunakaran, Nagavedi S Umapathy, Muthusamy Thangaraju, Takahiro Hatanaka, Shiro Itagaki, David H Munn, Puttur D Prasad, Vadivel Ganapathy. Interaction of tryptophan derivatives with SLC6A14 (ATB0,+) reveals the potential of the transporter as a drug target for cancer chemotherapy.
The Biochemical journal.
2008 Sep; 414(3):343-55. doi:
10.1042/bj20080622. [PMID: 18522536] - Kanishka Mohib, Shuang Wang, Qiunong Guan, Andrew L Mellor, Hongtao Sun, Caigan Du, Anthony M Jevnikar. Indoleamine 2,3-dioxygenase expression promotes renal ischemia-reperfusion injury.
American journal of physiology. Renal physiology.
2008 Jul; 295(1):F226-34. doi:
10.1152/ajprenal.00567.2007. [PMID: 18480171] - Lee Jia, Karen Schweikart, Joseph Tomaszewski, John G Page, Patricia E Noker, Sarah A Buhrow, Joel M Reid, Matthew M Ames, David H Munn. Toxicology and pharmacokinetics of 1-methyl-d-tryptophan: absence of toxicity due to saturating absorption.
Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.
2008 Jan; 46(1):203-11. doi:
10.1016/j.fct.2007.07.017. [PMID: 17868966] - Xuelian Li, Suiqi Gui, Haiyan Wang. Effect of Kidney-replenishing herb on the indoleamine 2,3-dioxygenase of human syncytiotrophoblasts cultured in vitro and the balance of helper T-cell cytokines.
Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology.
2007 Nov; 23(11):653-61. doi:
10.1080/09513590701665060. [PMID: 17999277] - Kanishka Mohib, Qiunong Guan, Hong Diao, Caigan Du, Anthony M Jevnikar. Proapoptotic activity of indoleamine 2,3-dioxygenase expressed in renal tubular epithelial cells.
American journal of physiology. Renal physiology.
2007 Sep; 293(3):F801-12. doi:
10.1152/ajprenal.00044.2007. [PMID: 17609291] - P Szylman, O S Better, C Chaimowitz, A Rosler. Role of hyperkalemia in the metabolic acidosis of isolated hypoaldosteronism.
The New England journal of medicine.
1976 Feb; 294(7):361-5. doi:
10.1056/nejm197602122940703. [PMID: 1674]