Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMIKMA9)

• Drug Name: CG-100649 Drug Info
• Synonyms: Polmacoxib; 301692-76-2; UNII-IJ34D6YPAO; CG100649; IJ34D6YPAO; 4-(3-(3-fluorophenyl)-5,5-dimethyl-4-oxo-4,5-dihydrofuran-2-yl)benzenesulfonamide; 4-[3-(3-Fluorophenyl)-5,5-Dimethyl-4-Oxidanylidene-Furan-2-Yl]benzenesulfonamide; 4-(3-(3-Fluorophenyl)-5,5-dimethyl-4-oxo-4,5-dihydrofuran-2-yl)-benzenesulfonamide; Polmacoxib [USAN:INN]; CG-100649; Acelex (S. Korea); CG 100649; Polmacoxib (USAN/INN); SCHEMBL3233093; CHEMBL166863; GTPL8316; EX-A601; IJWPAFMIFNSIGD-UHFFFAOYSA-N; ZINC589683; BCP15550; AKOS025149767; SB17177; DB12399

Indication

Disease Entry	ICD 11	Status	REF
Arthritis	FA20	Phase 3	[1]

• Cross-matching ID:
  PubChem CID: 9841854
  CAS Number: CAS 301692-76-2
  TTD Drug ID: DMIKMA9

Molecule-Related Drug Atlas

Drug(s) Targeting Carbonic anhydrase I (CA-I)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Salicyclic acid	DM2F8XZ	Acne vulgaris	ED80	Approved	[4]
Ethoxzolamide	DMVO4ED	Glaucoma/ocular hypertension	9C61	Approved	[5]
Dichlorphenamide	DMH7IDQ	Chronic glaucoma	9C61.0Z	Approved	[5]
Methazolamide	DM7J2TA	Glaucoma/ocular hypertension	9C61	Approved	[6]
Acetazolamide	DM1AF5U	Absence epilepsy		Approved	[5]
Curcumin	DMQPH29	Solid tumour/cancer	2A00-2F9Z	Phase 3	[7]
PARABEN	DMEW5Z8	N. A.	N. A.	Phase 3	[8]
PHENOL	DM1QSM3	N. A.	N. A.	Phase 2/3	[7]
Coumate	DMVKW0N	Breast cancer	2C60-2C65	Phase 2	[9]
SULFAMIDE	DMMAS3K	N. A.	N. A.	Phase 1	[10]

Drug(s) Targeting Carbonic anhydrase II (CA-II)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Salicyclic acid	DM2F8XZ	Acne vulgaris	ED80	Approved	[4]
Sulfamylon	DMIO1K0	Bacterial infection	1A00-1C4Z	Approved	[11]
Dorzolamide	DMA17D0	Ocular hypertension	9C61.01	Approved	[12]
Chlorothiazide	DMLHESP	Chronic heart failure	BD1Z	Approved	[13]
Ethoxzolamide	DMVO4ED	Glaucoma/ocular hypertension	9C61	Approved	[14]
Dichlorphenamide	DMH7IDQ	Chronic glaucoma	9C61.0Z	Approved	[14]
Cyclothiazide	DMJ4AWC	Congestive heart failure	BD10	Approved	[15]
Ethinamate	DMK57GB	Insomnia	7A00-7A0Z	Approved	[16]
Benzthiazide	DMQWZ0H	High blood pressure	BA00	Approved	[17]
Curcumin	DMQPH29	Solid tumour/cancer	2A00-2F9Z	Phase 3	[7]

Drug(s) Targeting Prostaglandin G/H synthase 2 (COX-2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ibuprofen	DM8VCBE	Dysmenorrhea	GA34.3	Approved	[18]
Naproxen	DMZ5RGV	Bursitis		Approved	[19]
Etodolac	DM6WJO9	Osteoarthritis	FA00-FA05	Approved	[20]
Indomethacin	DMSC4A7	Bursitis		Approved	[5]
Celecoxib	DM6LOQU	Dysmenorrhea	GA34.3	Approved	[21]
Nabumetone	DMAT2XH	Osteoarthritis	FA00-FA05	Approved	[22]
Rofecoxib	DM3P5DA	Osteoarthritis	FA00-FA05	Approved	[23]
Flurbiprofen	DMGN4BY	Osteoarthritis	FA00-FA05	Approved	[24]
Eicosapentaenoic acid/docosa-hexaenoic acid	DMMUCG4	Hypertriglyceridemia	5C80.1	Approved	[25]
Aminosalicylic Acid	DMENSL5	Crohn disease	DD70	Approved	[5]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Carbonic anhydrase I (CA-I)	TTHQPL7	CAH1_HUMAN	Inhibitor	[2]
Carbonic anhydrase II (CA-II)	TTANPDJ	CAH2_HUMAN	Inhibitor	[2]
Prostaglandin G/H synthase 2 (COX-2)	TTVKILB	PGH2_HUMAN	Inhibitor	[3]

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: 8316).
• [2] 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.
• [3] Pharmacokinetic, pharmacodynamic, and safety/tolerability profiles of CG100649, a novel COX-2 inhibitor: results of a phase i, randomized, multiple-dose study in healthy Korean men and women. Clin Ther. 2015 Jan 1;37(1):197-210.
• [4] 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.
• [5] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [6] 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).
• [7] Carbonic anhydrase inhibitors. Antioxidant polyphenols effectively inhibit mammalian isoforms I-XV. Bioorg Med Chem Lett. 2010 Sep 1;20(17):5050-3.
• [8] 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.
• [9] 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.
• [10] Carbonic anhydrase inhibitors. Inhibition of the newly isolated murine isozyme XIII with anions. Bioorg Med Chem Lett. 2004 Nov 1;14(21):5435-9.
• [11] Sulfonamide linked neoglycoconjugates--a new class of inhibitors for cancer-associated carbonic anhydrases. J Med Chem. 2010 Apr 8;53(7):2913-26.
• [12] Carbonic anhydrase inhibitors. Inhibition studies of a coral secretory isoform by sulfonamides. Bioorg Med Chem. 2009 Jul 15;17(14):5054-8.
• [13] 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.
• [14] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [15] Selective effect of thiazides on the human osteoblast-like cell line MG-63. Kidney Int. 1996 Nov;50(5):1476-82.
• [16] Inhibition of carbonic anhydrases I and II by N-unsubstituted carbamate esters. J Biol Chem. 1992 Dec 15;267(35):25044-50.
• [17] Nature of the inhibition of carbonic anhydrase by acetazolamide and benzthiazide. J Pharmacol Exp Ther. 1961 Mar;131:271-4.
• [18] Maternal toxicity of nonsteroidal anti-inflammatory drugs as an important factor affecting prenatal development. Reprod Toxicol. 2009 Sep;28(2):239-44.
• [19] 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.
• [20] 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.
• [21] Pfizer. Product Development Pipeline. March 31 2009.
• [22] 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.
• [23] Privileged structures: a useful concept for the rational design of new lead drug candidates. Mini Rev Med Chem. 2007 Nov;7(11):1108-19.
• [24] 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.
• [25] Cox-2 inhibitory effects of naturally occurring and modified fatty acids. J Nat Prod. 2001 Jun;64(6):745-9.