General Information of Drug (ID: DMQPH29)

Drug Name
Curcumin
Synonyms
curcumin; 458-37-7; Diferuloylmethane; Natural yellow 3; Turmeric yellow; Turmeric; Curcuma; Kacha haldi; Gelbwurz; Indian saffron; Curcumin I; Souchet; Halud; Halad; Haidr; Haldar; Merita earth; Yellow Ginger; Terra Merita; Yellow Root; Safran d'Inde; Yo-Kin; Golden seal; Curcuma oil; Orange Root; Oils, curcuma; CI Natural Yellow 3; Curcumine; Hydrastis; Indian turmeric; Yellow puccoon; Turmeric extract; Diferaloylmethane; Kurkumin [Czech]; (1E,6E)-1,7-Bis(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione; Tumeric yellow; Turmeric oil
Indication
Disease Entry ICD 11 Status REF
Solid tumour/cancer 2A00-2F9Z Phase 3 [1], [2]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 368.4
Topological Polar Surface Area (xlogp) 3.2
Rotatable Bond Count (rotbonds) 8
Hydrogen Bond Donor Count (hbonddonor) 2
Hydrogen Bond Acceptor Count (hbondacc) 6
ADMET Property
Elimination
Following oral administration of curcumin to rats at a dose of 1 g/kg bw, about 75% of dose was excreted in the faeces and only traces of the compound was detected in the urine [3]
Metabolism
The drug is metabolized via O-conjugation [4]
Chemical Identifiers
Formula
C21H20O6
IUPAC Name
(1E,6E)-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione
Canonical SMILES
COC1=C(C=CC(=C1)/C=C/C(=O)CC(=O)/C=C/C2=CC(=C(C=C2)O)OC)O
InChI
InChI=1S/C21H20O6/c1-26-20-11-14(5-9-18(20)24)3-7-16(22)13-17(23)8-4-15-6-10-19(25)21(12-15)27-2/h3-12,24-25H,13H2,1-2H3/b7-3+,8-4+
InChIKey
VFLDPWHFBUODDF-FCXRPNKRSA-N
Cross-matching ID
PubChem CID
969516
ChEBI ID
CHEBI:3962
CAS Number
458-37-7
DrugBank ID
DB11672
TTD ID
D07SDQ
VARIDT ID
DR00559
INTEDE ID
DR1941

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Albendazole monooxygenase (CYP3A4) TTXV4FI CP3A4_HUMAN Inhibitor [5]
Amyloid beta A4 protein (APP) TTE4KHA A4_HUMAN Inhibitor [6]
Carbonic anhydrase (CA) TTUNARX NOUNIPROTAC Inhibitor [7]
Carbonic anhydrase I (CA-I) TTHQPL7 CAH1_HUMAN Inhibitor [7]
Carbonic anhydrase II (CA-II) TTANPDJ CAH2_HUMAN Inhibitor [7]
Carbonic anhydrase IV (CA-IV) TTZHA0O CAH4_HUMAN Inhibitor [7]
Carbonic anhydrase IX (CA-IX) TT2LVK8 CAH9_HUMAN Inhibitor [7]
Carbonic anhydrase VI (CA-VI) TTCFSPE CAH6_HUMAN Inhibitor [7]
Carbonic anhydrase XII (CA-XII) TTSYM0R CAH12_HUMAN Inhibitor [7]
Carbonic anhydrase XIV (CA-XIV) TTEYTKG CAH14_HUMAN Inhibitor [7]
DNA [cytosine-5]-methyltransferase (DNMT) TTHVCUP NOUNIPROTAC Inhibitor [8]
DNA [cytosine-5]-methyltransferase 3B (DNMT3B) TT6VZ78 DNM3B_HUMAN Inhibitor [8]
Matrix metalloproteinase-13 (MMP-13) TTHY57M MMP13_HUMAN Inhibitor [9]
Matrix metalloproteinase-9 (MMP-9) TT6X50U MMP9_HUMAN Inhibitor [10]
Multidrug resistance protein (MDR) TT0JLSD NOUNIPROTAC Inhibitor [11]
Nitric-oxide synthase inducible (NOS2) TTF10I9 NOS2_HUMAN Inhibitor [12]
Prostaglandin G/H synthase 1 (COX-1) TT8NGED PGH1_HUMAN Inhibitor [13]
Prostaglandin G/H synthase 2 (COX-2) TTVKILB PGH2_HUMAN Inhibitor [13]
Xanthine dehydrogenase/oxidase (XDH) TT7RJY8 XDH_HUMAN Inhibitor [14]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [15]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
UDP-glucuronosyltransferase 1A1 (UGT1A1) DEYGVN4 UD11_HUMAN Substrate [16]
UDP-glucuronosyltransferase 1A9 (UGT1A9) DE85D2P UD19_HUMAN Substrate [16]
UDP-glucuronosyltransferase 1A8 (UGT1A8) DE2GB8N UD18_HUMAN Substrate [16]
UDP-glucuronosyltransferase 1A7 (UGT1A7) DEZO4N3 UD17_HUMAN Substrate [16]
NADPH-dependent curcumin reductase (curA) DEZWDKE CURA_ECOLI Substrate [17]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Solid tumour/cancer
ICD Disease Classification 2A00-2F9Z
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Prostaglandin G/H synthase 2 (COX-2) DTT PTGS2 7.93E-04 -0.29 -0.34
Amyloid beta A4 protein (APP) DTT APP 1.60E-02 -0.07 -0.31
Prostaglandin G/H synthase 1 (COX-1) DTT PTGS1 3.97E-03 0.16 0.43
P-glycoprotein 1 (ABCB1) DTP P-GP 9.39E-02 1.07E-01 2.80E-01
UDP-glucuronosyltransferase 1A1 (UGT1A1) DME UGT1A1 1.10E-01 -5.91E-02 -3.60E-01
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7000).
2 Nanocurcumin: a promising therapeutic advancement over native curcumin. Crit Rev Ther Drug Carrier Syst. 2013;30(4):331-68.
3 An FDA phase I clinical trial of quinacrine sterilization (QS). Int J Gynaecol Obstet. 2003 Oct;83 Suppl 2:S45-9.
4 FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clin Cancer Res. 2014 Sep 1;20(17):4436-41.
5 Structure-activity relationships for the inhibition of recombinant human cytochromes P450 by curcumin analogues. Eur J Med Chem. 2008 Aug;43(8):1621-31.
6 Curcumin and dehydrozingerone derivatives: synthesis, radiolabeling, and evaluation for beta-amyloid plaque imaging. J Med Chem. 2006 Oct 5;49(20):6111-9.
7 Carbonic anhydrase inhibitors. Antioxidant polyphenols effectively inhibit mammalian isoforms I-XV. Bioorg Med Chem Lett. 2010 Sep 1;20(17):5050-3.
8 Novel and selective DNA methyltransferase inhibitors: Docking-based virtual screening and experimental evaluation. Bioorg Med Chem. 2010 Jan 15;18(2):822-9.
9 High throughput screening of potentially selective MMP-13 exosite inhibitors utilizing a triple-helical FRET substrate. Bioorg Med Chem. 2009 Feb 1;17(3):990-1005.
10 Synthesis and biological evaluation of curcuminoid pyrazoles as new therapeutic agents in inflammatory bowel disease: effect on matrix metalloprote... Bioorg Med Chem. 2009 Feb 1;17(3):1290-6.
11 Thiazolides: a new class of antiviral drugs. Expert Opin Drug Metab Toxicol. 2009 Jun;5(6):667-74.
12 A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases. Proc Natl Acad Sci U S A. 2007 Dec 18;104(51):20523-8.
13 Design, synthesis, biological evaluation and molecular docking of curcumin analogues as antioxidant, cyclooxygenase inhibitory and anti-inflammator... Bioorg Med Chem Lett. 2005 Apr 1;15(7):1793-7.
14 Inhibition studies of bovine xanthine oxidase by luteolin, silibinin, quercetin, and curcumin. J Nat Prod. 2009 Apr;72(4):725-31.
15 Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
16 Differential and special properties of the major human UGT1-encoded gastrointestinal UDP-glucuronosyltransferases enhance potential to control chemical uptake. J Biol Chem. 2004 Jan 9;279(2):1429-41.
17 Discovery of the curcumin metabolic pathway involving a unique enzyme in an intestinal microorganism. Proc Natl Acad Sci U S A. 2011 Apr 19;108(16):6615-20.
18 Functional significance of UDP-glucuronosyltransferase variants in the metabolism of active tamoxifen metabolites. Cancer Res. 2009 Mar 1;69(5):1892-900.
19 Functional characterization of human and cynomolgus monkey UDP-glucuronosyltransferase 1A1 enzymes. Life Sci. 2010 Aug 14;87(7-8):261-8.
20 Effect of UDP-glucuronosyltransferase (UGT) 1A polymorphism (rs8330 and rs10929303) on glucuronidation status of acetaminophen. Dose Response. 2017 Sep 11;15(3):1559325817723731.
21 UDP-glucuronosyltransferase 1A1 is the principal enzyme responsible for etoposide glucuronidation in human liver and intestinal microsomes: structural characterization of phenolic and alcoholic glucuronides of etoposide and estimation of enzyme kinetics. Drug Metab Dispos. 2007 Mar;35(3):371-80.
22 Interindividual variability in pharmacokinetics of generic nucleoside reverse transcriptase inhibitors in TB/HIV-coinfected Ghanaian patients: UGT2B7*1c is associated with faster zidovudine clearance and glucuronidation. J Clin Pharmacol. 2009 Sep;49(9):1079-90.
23 Effect of aging on glucuronidation of valproic acid in human liver microsomes and the role of UDP-glucuronosyltransferase UGT1A4, UGT1A8, and UGT1A10. Drug Metab Dispos. 2009 Jan;37(1):229-36.
24 Characterization of rat intestinal microsomal UDP-glucuronosyltransferase activity toward mycophenolic acid. Drug Metab Dispos. 2006 Sep;34(9):1632-9.
25 Drug-drug interactions for UDP-glucuronosyltransferase substrates: a pharmacokinetic explanation for typically observed low exposure (AUCi/AUC) ratios. Drug Metab Dispos. 2004 Nov;32(11):1201-8.
26 Substrate-dependent modulation of UDP-glucuronosyltransferase 1A1 (UGT1A1) by propofol in recombinant human UGT1A1 and human liver microsomes. Basic Clin Pharmacol Toxicol. 2007 Sep;101(3):211-4.
27 Identification and preliminary characterization of UDP-glucuronosyltransferases catalyzing formation of ethyl glucuronide. Anal Bioanal Chem. 2014 Apr;406(9-10):2325-32.
28 Polymorphic expression of UGT1A9 is associated with variable acetaminophen glucuronidation in neonates: a population pharmacokinetic and pharmacogenetic study. Clin Pharmacokinet. 2018 Oct;57(10):1325-1336.
29 Glucuronidation of nonsteroidal anti-inflammatory drugs: identifying the enzymes responsible in human liver microsomes. Drug Metab Dispos. 2005 Jul;33(7):1027-35.
30 Pharmacokinetic interaction involving sorafenib and the calcium-channel blocker felodipine in a patient with hepatocellular carcinoma. Invest New Drugs. 2011 Dec;29(6):1511-4.
31 Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
32 The evolution of population pharmacokinetic models to describe the enterohepatic recycling of mycophenolic acid in solid organ transplantation and autoimmune disease. Clin Pharmacokinet. 2011 Jan;50(1):1-24.
33 The UDP-glucuronosyltransferase 1A9 enzyme is a peroxisome proliferator-activated receptor alpha and gamma target gene. J Biol Chem. 2003 Apr 18;278(16):13975-83.
34 Uridine 5'-diphospho-glucuronosyltransferase genetic polymorphisms and response to cancer chemotherapy. Future Oncol. 2010 Apr;6(4):563-85.
35 Empagliflozin (Jardiance): a novel SGLT2 inhibitor for the treatment of type-2 diabetes. P T. 2015 Jun;40(6):364-8.
36 Drug-drug interaction potential of darolutamide: in vitro and clinical studies. Eur J Drug Metab Pharmacokinet. 2019 Dec;44(6):747-759.
37 Glucuronidation of active tamoxifen metabolites by the human UDP glucuronosyltransferases. Drug Metab Dispos. 2007 Nov;35(11):2006-14.
38 Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
39 MDR1 (ABCB1) G1199A (Ser400Asn) polymorphism alters transepithelial permeability and sensitivity to anticancer agents. Cancer Chemother Pharmacol. 2009 Jun;64(1):183-8.
40 Folate transporter expression decreases in the human placenta throughout pregnancy and in pre-eclampsia. Pregnancy Hypertens. 2012 Apr;2(2):123-31.
41 Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res. 2001 Dec;18(12):1660-8.
42 Antiestrogens and steroid hormones: substrates of the human P-glycoprotein. Biochem Pharmacol. 1994 Jul 19;48(2):287-92.
43 Association of genetic polymorphisms in the influx transporter SLCO1B3 and the efflux transporter ABCB1 with imatinib pharmacokinetics in patients with chronic myeloid leukemia. Ther Drug Monit. 2011 Apr;33(2):244-50.
44 A 2-year randomised, double-blind, placebo-controlled, multicentre study of oral selective iNOS inhibitor, cindunistat (SD-6010), in patients with symptomatic osteoarthritis of the knee. Ann Rheum Dis. 2013 Feb;72(2):187-95.
45 Lipopolysaccharide and monophosphoryl lipid A differentially regulate interleukin-12, gamma interferon, and interleukin-10 mRNA production in murine macrophages. Infect Immun. 1997 Aug;65(8):3239-47.
46 Nitric oxide associated with iNOS expression inhibits acetylcholinesterase activity and induces memory impairment during acute hypobaric hypoxia. Brain Res. 2008 Sep 16;1230:138-49.
47 GW274150, a potent and highly selective inhibitor of iNOS, reduces experimental renal ischemia/reperfusion injury. Kidney Int. 2003 Mar;63(3):853-65.
48 Shear stress induces iNOS expression in cultured smooth muscle cells: role of oxidative stress. Am J Physiol Cell Physiol. 2000 Dec;279(6):C1880-8.
49 HP-228, a novel synthetic peptide, inhibits the induction of nitric oxide synthase in vivo but not in vitro. J Pharmacol Exp Ther. 1995 Nov;275(2):584-91.
50 Efficacy of CR3294, a new benzamidine derivative, in the prevention of 5-fluorouracil-induced gastrointestinal mucositis and diarrhea in mice. Cancer Chemother Pharmacol. 2010 October; 66(5): 819-827.
51 WO patent application no. 2014,0214,08, Method for treating cancer by anticancer agent co-administration.
52 Critical role of L-arginine in endothelial cell survival during oxidative stress. Circulation. 2003 May 27;107(20):2607-14.
53 Inhibitory effects of aminoguanidine on thyroid follicular carcinoma development in inflamed capsular regions of rats treated with sulfadimethoxine... Cancer Sci. 2009 Oct;100(10):1794-800.
54 Carbonic anhydrase inhibitors: inhibition of mammalian isoforms I-XIV with a series of substituted phenols including paracetamol and salicylic acid. Bioorg Med Chem. 2008 Aug 1;16(15):7424-8.
55 Cloning, expression, post-translational modifications and inhibition studies on the latest mammalian carbonic anhydrase isoform, CA XV. J Med Chem. 2009 Feb 12;52(3):646-54.
56 Carbonic anhydrase inhibitors. Inhibition of mammalian isoforms I-XIV with a series of natural product polyphenols and phenolic acids. Bioorg Med Chem. 2010 Mar 15;18(6):2159-2164.
57 Carbonic anhydrase inhibitors. Interaction of the antitumor sulfamate EMD 486019 with twelve mammalian carbonic anhydrase isoforms: Kinetic and X-r... Bioorg Med Chem Lett. 2008 Aug 1;18(15):4282-6.
58 An Antibody-Drug Conjugate Targeting MUC1-Associated Carbohydrate CA6 Shows Promising Antitumor Activities. Mol Cancer Ther. 2020 Aug;19(8):1660-1669.
59 Polyamines inhibit carbonic anhydrases by anchoring to the zinc-coordinated water molecule. J Med Chem. 2010 Aug 12;53(15):5511-22.
60 Deciphering the mechanism of carbonic anhydrase inhibition with coumarins and thiocoumarins. J Med Chem. 2010 Jan 14;53(1):335-44.
61 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
62 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2597).
63 Understanding the Dual Inhibition of COX-2 and Carbonic Anhydrase-II by Celecoxib and CG100649 Using Density Functional Theory Calculations and other Molecular Modelling Approaches. Protein Pept Lett. 2015;22(10):903-12.
64 Carbonic anhydrase inhibitors. Inhibition of the newly isolated murine isozyme XIII with anions. Bioorg Med Chem Lett. 2004 Nov 1;14(21):5435-9.
65 Benzquinamide inhibits P-glycoprotein mediated drug efflux and potentiates anticancer agent cytotoxicity in multidrug resistant cells. Oncol Res. 1992;4(8-9):359-65.
66 Clinical pipeline report, company report or official report of Spectrum Phamaceuticals (2009).
67 Intracellular levels of two cyclosporin derivatives valspodar (PSC 833) and cyclosporin a closely associated with multidrug resistance-modulating activity in sublines of human colorectal adenocarcinoma HCT-15. Jpn J Cancer Res. 2001 Oct;92(10):1116-26.
68 P-glycoprotein as a drug target in the treatment of multidrug resistant cancer. Curr Drug Targets. 2000 Jul;1(1):85-99.
69 Sulfonamide linked neoglycoconjugates--a new class of inhibitors for cancer-associated carbonic anhydrases. J Med Chem. 2010 Apr 8;53(7):2913-26.
70 Carbonic anhydrase inhibitors. Inhibition studies of a coral secretory isoform by sulfonamides. Bioorg Med Chem. 2009 Jul 15;17(14):5054-8.
71 Localization of diuretic effects along the loop of Henle: an in vivo microperfusion study in rats. Clin Sci (Lond). 2000 Apr;98(4):481-8.
72 The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
73 Selective effect of thiazides on the human osteoblast-like cell line MG-63. Kidney Int. 1996 Nov;50(5):1476-82.
74 Inhibition of carbonic anhydrases I and II by N-unsubstituted carbamate esters. J Biol Chem. 1992 Dec 15;267(35):25044-50.
75 Nature of the inhibition of carbonic anhydrase by acetazolamide and benzthiazide. J Pharmacol Exp Ther. 1961 Mar;131:271-4.
76 Carbonic anhydrase inhibitors: inhibition of the transmembrane isozyme XIV with sulfonamides. Bioorg Med Chem Lett. 2005 Sep 1;15(17):3828-33.
77 Acetylenic TACE inhibitors. Part 3: Thiomorpholine sulfonamide hydroxamates. Bioorg Med Chem Lett. 2006 Mar 15;16(6):1605-9.
78 Potent, selective spiropyrrolidine pyrimidinetrione inhibitors of MMP-13. Bioorg Med Chem Lett. 2007 Dec 1;17(23):6529-34.
79 Gelatinase inhibitors: a patent review (2011-2017).Expert Opin Ther Pat. 2018 Jan;28(1):31-46.
80 Discovery and characterization of a novel inhibitor of matrix metalloprotease-13 that reduces cartilage damage in vivo without joint fibroplasia si... J Biol Chem. 2007 Sep 21;282(38):27781-91.
81 Structure-based design of potent and selective inhibitors of collagenase-3 (MMP-13). Bioorg Med Chem Lett. 2005 Feb 15;15(4):1101-6.
82 Heterocycle-based MMP inhibitors with P2' substituents. Bioorg Med Chem Lett. 2001 Apr 23;11(8):1009-13.
83 Peptidomimetic C5a receptor antagonists with hydrophobic substitutions at the C-terminus: increased receptor specificity and in vivo activity. Bioorg Med Chem Lett. 2006 Oct 1;16(19):5088-92.
84 Discovery and evaluation of 4-(2-(4-chloro-1H-pyrazol-1-yl)ethylamino)-3-(6-(1-(3-fluoropropyl)piperidin-4-yl)-4-methyl-1H-benzo[d]imidazol-2-yl)py... J Med Chem. 2008 Oct 9;51(19):5897-900.
85 Novel substituted pyridinyl imidazoles as potent anticytokine agents with low activity against hepatic cytochrome P450 enzymes. J Med Chem. 2003 Jul 17;46(15):3230-44.
86 Design, synthesis, and biological evaluation of (hydroxyphenyl)naphthalene and -quinoline derivatives: potent and selective nonsteroidal inhibitors... J Med Chem. 2008 Apr 10;51(7):2158-69.
87 Role of hydrophobic substituents on the terminal nitrogen of histamine in receptor binding and agonist activity: development of an orally active hi... J Med Chem. 2010 May 13;53(9):3840-4.
88 New insights into the SAR and binding modes of bis(hydroxyphenyl)thiophenes and -benzenes: influence of additional substituents on 17beta-hydroxyst... J Med Chem. 2009 Nov 12;52(21):6724-43.
89 Allopurinol: xanthine oxidase inhibitor. Tex Med. 1966 Jan;62(1):100-1.
90 Clinical pipeline report, company report or official report of Takeda (2009).
91 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2021
92 Oxypurinol as an inhibitor of xanthine oxidase-catalyzed production of superoxide radical. Biochem Pharmacol. 1988 Jan 15;37(2):349-52.
93 Inhibition of cow's milk xanthine oxidase by flavonoids. J Nat Prod. 1988 Mar-Apr;51(2):345-8.
94 QT/QTc study conducted in Japanese adult healthy subjects: a novel xanthine oxidase inhibitor topiroxostat was not associated with QT prolongation. J Clin Pharmacol. 2014 Apr;54(4):446-52.
95 Clinical pipeline report, company report or official report of Teijin Pharma.
96 Pharmacokinetics, pharmacodynamics, and tolerability of LC350189, a novel xanthine oxidase inhibitor, in healthy subjects. Drug Des Devel Ther. 2015 Aug 31;9:5033-49.
97 An updated patent review: xanthine oxidase inhibitors for the treatment of hyperuricemia and gout (2011-2015).Expert Opin Ther Pat. 2017 Mar;27(3):311-345.
98 Carbonic anhydrase inhibitors: Inhibition of the new membrane-associated isoform XV with phenols. Bioorg Med Chem Lett. 2008 Jun 15;18(12):3593-6.
99 Carbonic anhydrase inhibitors. Interaction of indapamide and related diuretics with 12 mammalian isozymes and X-ray crystallographic studies for th... Bioorg Med Chem Lett. 2008 Apr 15;18(8):2567-73.
100 Anti-obesity drugs. Expert Opin Pharmacother. 2008 Jun;9(8):1339-50.
101 Carbonic anhydrase inhibitors: crystallographic and solution binding studies for the interaction of a boron-containing aromatic sulfamide with mamm... Bioorg Med Chem Lett. 2010 Jun 15;20(12):3601-5.
102 Carbonic anhydrase inhibitors as antitumor/antimetastatic agents: a patent review (2008-2018).Expert Opin Ther Pat. 2018 Oct;28(10):729-740.
103 Carbonic anhydrase inhibitors. Inhibition of the membrane-bound human and bovine isozymes IV with sulfonamides. Bioorg Med Chem Lett. 2005 Feb 15;15(4):1149-54.
104 Carbonic anhydrase inhibitors. Interaction of isozymes I, II, IV, V, and IX with carboxylates. Bioorg Med Chem Lett. 2005 Feb 1;15(3):573-8.
105 DP-b99 modulates matrix metalloproteinase activity and neuronal plasticity. PLoS One. 2014 Jun 11;9(6):e99789.
106 National Cancer Institute Drug Dictionary (drug id 747683).
107 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
108 Antibodies and venom peptides: new modalities for ion channels. Nat Rev Drug Discov. 2019 May;18(5):339-357.
109 Neovastat, a naturally occurring multifunctional antiangiogenic drug, in phase III clinical trials. Semin Oncol. 2001 Dec;28(6):620-5.
110 The C50T polymorphism of the cyclooxygenase-1 gene and the risk of thrombotic events during low-dose therapy with acetyl salicylic acid. Thromb Haemost. 2008 Jul;100(1):70-5.
111 Comparative inhibitory activity of rofecoxib, meloxicam, diclofenac, ibuprofen, and naproxen on COX-2 versus COX-1 in healthy volunteers. J Clin Pharmacol. 2000 Oct;40(10):1109-20.
112 How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
113 Cox-2 inhibitory effects of naturally occurring and modified fatty acids. J Nat Prod. 2001 Jun;64(6):745-9.
114 Comparison of cyclooxygenase inhibitory activity and ocular anti-inflammatory effects of ketorolac tromethamine and bromfenac sodium. Curr Med Res Opin. 2006 Jun;22(6):1133-40.
115 Ouellet M, Percival MD: Effect of inhibitor time-dependency on selectivity towards cyclooxygenase isoforms. Biochem J. 1995 Feb 15;306 ( Pt 1):247-51.
116 Differential binding mode of diverse cyclooxygenase inhibitors. J Mol Graph Model. 2002 Mar;20(5):359-71.
117 Differential metabolism of dihomo-gamma-linolenic acid and arachidonic acid by cyclo-oxygenase-1 and cyclo-oxygenase-2: implications for cellular synthesis of prostaglandin E1 and prostaglandin E2. Biochem J. 2002 Jul 15;365(Pt 2):489-96.
118 Carbonic anhydrase inhibitors: E7070, a sulfonamide anticancer agent, potently inhibits cytosolic isozymes I and II, and transmembrane, tumor-assoc... Bioorg Med Chem Lett. 2004 Jan 5;14(1):217-23.
119 Potential role of (124)I-girentuximab in the presurgical diagnosis of clear-cell renal cell cancer. Biologics. 2012;6:395-407.
120 Carbonic anhydrase inhibitors. Inhibition of isozymes I, II, IV, V, and IX with anions isosteric and isoelectronic with sulfate, nitrate, and carbo... Bioorg Med Chem Lett. 2005 Feb 1;15(3):567-71.
121 Therapeutic mechanism and efficacy of the antibody-drug conjugate BAY 79-4620 targeting human carbonic anhydrase 9. Mol Cancer Ther. 2012 Feb;11(2):340-9.
122 Application of monoclonal antibody G250 recognizing carbonic anhydrase IX in renal cell carcinoma. Int J Mol Sci. 2013 May 29;14(6):11402-23.
123 DNA methyltransferase inhibitors: an updated patent review (2012-2015).Expert Opin Ther Pat. 2016 Sep;26(9):1017-30.
124 Constrained (l-)-S-adenosyl-l-homocysteine (SAH) analogues as DNA methyltransferase inhibitors. Bioorg Med Chem Lett. 2009 May 15;19(10):2742-6.
125 Maternal toxicity of nonsteroidal anti-inflammatory drugs as an important factor affecting prenatal development. Reprod Toxicol. 2009 Sep;28(2):239-44.
126 Membranous nephropathy associated with the relatively selective cyclooxygenase-2 inhibitor, etodolac, in a patient with early rheumatoid arthritis. Intern Med. 2007;46(13):1055-8.
127 Pfizer. Product Development Pipeline. March 31 2009.
128 Renal effects of nabumetone, a COX-2 antagonist: impairment of function in isolated perfused rat kidneys contrasts with preserved renal function in vivo. Exp Nephrol. 2001;9(6):387-96.
129 Privileged structures: a useful concept for the rational design of new lead drug candidates. Mini Rev Med Chem. 2007 Nov;7(11):1108-19.
130 Flurbiprofen, a cyclooxygenase inhibitor, protects mice from hepatic ischemia/reperfusion injury by inhibiting GSK-3 signaling and mitochondrial permeability transition.Mol Med.2012 Sep 25;18:1128-35.
131 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
132 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
133 Phase 3 trials of solanezumab for mild-to-moderate Alzheimer's disease. N Engl J Med. 2014 Jan 23;370(4):311-21.
134 Passive anti-amyloid immunotherapy in Alzheimer's disease: What are the most promising targets . Immun Ageing. 2013; 10: 18.
135 Targeting soluble Abeta peptide with Tramiprosate for the treatment of brain amyloidosis. Neurobiol Aging. 2007 Apr;28(4):537-47.
136 Bapineuzumab: anti-beta-amyloid monoclonal antibodies for the treatment of Alzheimer's disease. Immunotherapy. 2010 Nov;2(6):767-82.
137 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
138 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
139 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2402).
140 Disease-modifying drugs in Alzheimer's disease. Drug Des Devel Ther. 2013; 7: 1471-1479.
141 The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid l... Leukemia. 2009 Jun;23(6):1019-28.
142 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)