ID
`
`Pharmacology
`
`Interactions
`
`References
`
`Trials
`
`Economics
`
`Properties
`
`Spectra
`
`Taxonomy
`
`0 Comments
`
`Targets (2) Enzymes (2) Carriers (1) Transporters (3) Biointeractions (9)
`
`Show Drugs with Similar Structures
`
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`
`Identification
`Identification
`
`Name
`
`Piroxicam
`
`Accession Number DB00554 (APRD01187)
`
`Type
`
`Groups
`
`Description
`
`Structure
`
`Small Molecule
`
`Approved, Investigational
`
`A cyclooxygenase inhibiting, non-steroidal anti-inflammatory agent (NSAID) that is well established in treating
`rheumatoid arthritis and osteoarthritis and used for musculoskeletal disorders, dysmenorrhea, and postoperative pain.
`Its long half-life enables it to be administered once daily. [PubChem]
`
`N
`
`O
`
`OH
`
`HN
`
`N
`
`O
`
`S
`
`O
`
`CH3
`
` MOL
`
`SDF
`
`3D-SDF
`
`PDB
`
`SMILES
`
`InChI
`
`
`
` View 3D Structure
`
`Synonyms
`
`4-Hydroxy-2-methyl-N-(2-pyridyl)-2H-1,2-benzothiazin-3-caboxyamid-1,1-dioxid
`
`Feldene
`
`Piroxicam
`
`Piroxicamum
`
`Pyroxycam
`
`External IDs
`
`
`
`Not Available
`
`Product
`
`Ingredients
`
`Not Available
`
`Show 10
`
` entries
`
`Approved
`Prescription
`Products
`
`Search
`
`Name
`
`Dosage
`
`Strength
`
`Route
`
`Labeller
`
`Alti-piroxicam-cap 10mg
`
`Capsule
`
`10 mg
`
`Oral
`
`Alti-piroxicam-cap 20mg
`
`Capsule
`
`20 mg
`
`Oral
`
`Dom-piroxicam
`
`Capsule
`
`10 mg
`
`Oral
`
`Dom-piroxicam
`
`Suppository 10 mg
`
`Rectal
`
`Dom-piroxicam
`
`Suppository 20 mg
`
`Rectal
`
`Dom-piroxicam
`
`Capsule
`
`20 mg
`
`Oral
`
`Altimed
`Pharma Inc.
`
`Altimed
`Pharma Inc.
`
`Dominion
`Pharmacal
`
`Dominion
`Pharmacal
`
`Dominion
`Pharmacal
`
`Dominion
`Pharmacal
`
`Marketing
`Start
`
`Marketing
`End
`
`1997-09-24
`
`2004-08-03
`
`1995-12-31
`
`2004-08-03
`
`Not
`applicable
`
`2016-10-25
`
`1995-12-31
`
`2016-10-25
`
`1995-12-31
`
`2016-10-25
`
`1999-10-25
`
`2016-10-25
`
`Feldene
`
`Capsule
`
`20 mg/1
`
`Oral
`
`Pfizer
`Laboratories
`
`1994-05-25 Not
`applicable
`
`Par Pharm., Inc.
`Exhibit 1059
`Page 001
`
`

`

`Feldene
`
`Feldene
`
`Capsule
`
`20 mg/1
`
`Oral
`
`Capsule
`
`10 mg/1
`
`Oral
`
`Div Pfizer Inc.
`
`Remedy
`Repack
`
`Pfizer
`Laboratories
`Div Pfizer Inc.
`
`2012-09-26
`
`2016-12-23
`
`1994-05-25 Not
`applicable
`
`Feldene Cap 10mg
`
`Capsule
`
`10 mg
`
`Oral
`
`Pfizer
`
`1981-12-31
`
`2002-09-06
`
`Approved Generic
`Prescription
`Products
`
`Show 10
`
` entries
`
`Showing 1 to 10 of 34 entries
`
`Previous
`
`1
`
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`
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`
`4
`
`Next
`
`Search
`
`Name
`
`Dosage
`
`Strength
`
`Route
`
`Labeller
`
`Apo Piroxicam Cap 10mg
`
`Capsule
`
`10 mg
`
`Oral
`
`Apo Piroxicam Cap 20mg
`
`Capsule
`
`20 mg
`
`Oral
`
`Feldene
`
`Capsule
`
`20 mg/1
`
`Oral
`
`Apotex
`Corporation
`
`Apotex
`Corporation
`
`Keltman
`Pharmaceuticals
`Inc.
`
`Marketing
`Start
`
`Marketing
`End
`
`1986-12-31 Not
`applicable
`
`1986-12-31 Not
`applicable
`
`2007-09-18 Not
`applicable
`
`Piroxicam
`
`Capsule
`
`10 mg/1
`
`Oral
`
`Rebel
`Distributors
`
`2009-11-12 Not
`applicable
`
`20 mg/1
`
`Oral
`
`Stat Rx USA
`
`Piroxicam
`
`Piroxicam
`
`Piroxicam
`
`Piroxicam
`
`Piroxicam
`
`Capsule
`
`Capsule
`
`20 mg/1
`
`Oral
`
`Capsule
`
`20 mg/1
`
`Oral
`
`Capsule
`
`20 mg/1
`
`Oral
`
`Capsule
`
`10 mg/1
`
`Oral
`
`2011-10-07 Not
`applicable
`
`A S Medication
`Solutions
`
`2010-01-05 Not
`applicable
`
`Golden State
`Medical Supply
`
`2010-01-05 Not
`applicable
`
`Mylan
`Pharmaceuticals
`
`2016-09-30 Not
`applicable
`
`Lake Erie
`Medical Dba
`Quality Care
`Produts Llc
`
`1994-10-19 Not
`applicable
`
`2013-06-27 Not
`applicable
`
`Piroxicam
`
`Capsule
`
`10 mg/1
`
`Oral
`
`Av Kare, Inc.
`
`Showing 1 to 10 of 46 entries
`
`Previous
`
`1
`
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`
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`
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`
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`
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`
`Approved Over the
`Counter Products
`
`Unapproved/Other
`
`Products
`
`Not Available
`
`Not Available
`
`International
`Brands
`
`Show 10
`
` entries
`
`Name
`
`Bruxicam
`
`Dolonex
`
`Erazon
`
`Geldène
`
`Improntal
`
`Roxam
`
`Roxiden
`
`Search
`
`Company
`
`Not Available
`
`Not Available
`
`Not Available
`
`Not Available
`
`Not Available
`
`Bosnalijek
`
`Not Available
`
`Par Pharm., Inc.
`Exhibit 1059
`Page 002
`
`

`

`Sasulen
`
`Solocalm
`
`Trast
`
`Not Available
`
`Not Available
`
`Not Available
`
`Showing 1 to 10 of 10 entries
`
`Previous
`
`1
`
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`
`Brand mixtures
`
`Show 10
`
` entries
`
`Name
`
`Therafeldamine
`
`Search
`
`Labeller
`
`Ingredients
`
`Physician Therapeutics Llc
`
`gamma-Aminobutyric acid / Piroxicam
`
`Categories
`
`Showing 1 to 1 of 1 entries
`
`Previous
`
`1
`
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`
`Analgesics
`Analgesics, Non-Narcotic
`Anti-Inflammatory Agents
`Anti-Inflammatory Agents, Non-Steroidal
`Antiinflammatory and Antirheumatic Products
`Antiinflammatory and Antirheumatic Products, Non-Steroids
`Antirheumatic Agents
`Central Nervous System Agents
`Cyclooxygenase Inhibitors
`Cytochrome P-450 CYP2C8 Inhibitors
`Cytochrome P-450 CYP2C8 Substrates
`Cytochrome P-450 CYP2C9 Inhibitors
`Cytochrome P-450 CYP2C9 Substrates
`Enzyme Inhibitors
`Musculo-Skeletal System
`Oxicams
`Peripheral Nervous System Agents
`Sensory System Agents
`Sulfur Compounds
`Thiazines
`
`UNII
`
`13T4O6VMAM
`
`
`
`CAS number
`
`36322-90-4
`
`Weight
`
`Average: 331.346
`Monoisotopic: 331.062676609
`
`Chemical Formula
`
`C H N O S
`15 13 3 4
`
`InChI Key
`
`QYSPLQLAKJAUJT-UHFFFAOYSA-N
`
`InChI
`
`IUPAC Name
`
`InChI=1S/C15H13N3O4S/c1-18-13(15(20)17-12-8-4-5-9-16-12)14(19)10-6-2-3-7-11(10)23(18,21)22/h2-
`9,19H,1H3,(H,16,17,20)
`4-hydroxy-2-methyl-1,1-dioxo-N-(pyridin-2-yl)-2H-1λ⁶,2-benzothiazine-3-carboxamide
`
`SMILES
`
`CN1C(C(=O)NC2=NC=CC=C2)=C(O)C2=C(C=CC=C2)S1(=O)=O
`
`Pharmacology
`Pharmacology
`
`Indication
`
`For treatment of osteoarthritis and rheumatoid arthritis.
`
`Structured
`Indications
`
`
`
`Ankylosing Spondylitis (AS)
`Rheumatoid Arthritis
`Synovitis of osteoarthritis
`
`Pharmacodynamics Piroxicam is in a class of drugs called nonsteroidal anti-inflammatory drugs (NSAIDs). Piroxicam works by reducing
`hormones that cause inflammation and pain in the body. Piroxicam is used to reduce the pain, inflammation, and
`stiffness caused by rheumatoid arthritis and osteoarthritis.
`
`Mechanism of
`action
`
`The antiinflammatory effect of Piroxicam may result from the reversible inhibition of cyclooxygenase, causing the
`peripheral inhibition of prostaglandin synthesis. The prostaglandins are produced by an enzyme called Cox-1. Piroxicam
`blocks the Cox-1 enzyme, resulting into the disruption of production of prostaglandins. Piroxicam also inhibits the
`
`Par Pharm., Inc.
`Exhibit 1059
`Page 003
`
`

`

`migration of leukocytes into sites of inflammation and prevents the formation of thromboxane A2, an aggregating agent,
`by the platelets.
`
`Target
`
`Kind
`
`Pharmacological action
`
`Actions
`
`Organism UniProt ID
`
`details
`
`details
`
` 
`
`Prostaglandin G/H synthase 2
`
`Protein
`
`yes
`
`inhibitor
`
`Human
`
`P35354
`
`Prostaglandin G/H synthase 1
`
`Protein
`
`unknown
`
`inhibitor
`
`Human
`
`P23219
`
`Related Articles
`
`Absorption
`
`Well absorbed following oral administration.
`
`Volume of
`distribution
`
`0.14 L/kg
`
`Protein binding
`
`Not Available
`
`Metabolism
`
`Renal
`
`Substrate
`
`Enzymes
`
`Product
`
`Piroxicam
`
`
`Cytochrome P450 2C9
`
`5'-Hydroxypiroxicam
`
`Details
`
`Route of
`elimination
`
`Piroxicam and its biotransformation products are excreted in urine and feces, with about twice as much appearing in the
`urine as in the feces. Approximately 5% of a piroxicam dose is excreted unchanged. However, a substantial portion of
`piroxicam elimination occurs by hepatic metabolism. Piroxicam is excreted into human milk.
`
`Half life
`
`30 to 86 hours
`
`Clearance
`
`Not Available
`
`Toxicity
`
`Symptoms of overdose include drowsiness, nausea, stomach pain, and/or vomiting.
`
`Affected organisms
`
`Humans and other mammals
`
`Pathways
`
`Pathway
`
`Piroxicam Action Pathway
`
`Not Available
`
`Not Available
`
`SNP Mediated
`Effects
`
`SNP Mediated
`Adverse Drug
`Reactions
`
`Interactions
`Interactions
`
`Drug Interactions
`
`Show 10
`
` entries
`
`Category
`
`Drug action
`
`SMPDB ID
`
`SMP00077
`
`Search
`
`Drug
`
`Interaction
`
`16-
`Bromoepiandrosterone
`
`The risk or severity of adverse effects can be increased when Piroxicam is
`combined with 16-Bromoepiandrosterone.
`
`Drug group
`
`Investigational
`
`19-
`norandrostenedione
`
`The risk or severity of adverse effects can be increased when Piroxicam is
`combined with 19-norandrostenedione.
`
`Experimental, Illicit
`
`4-Androstenedione
`
`The risk or severity of adverse effects can be increased when Piroxicam is
`combined with 4-Androstenedione.
`
`Experimental, Illicit
`
`5-androstenedione
`
`The risk or severity of adverse effects can be increased when Piroxicam is
`combined with 5-androstenedione.
`
`Experimental, Illicit
`
`Abciximab
`
`Abiraterone
`
`Acebutolol
`
`Aceclofenac
`
`Piroxicam may increase the anticoagulant activities of Abciximab.
`
`The serum concentration of Piroxicam can be increased when it is combined
`with Abiraterone.
`
`Piroxicam may decrease the antihypertensive activities of Acebutolol.
`
`The risk or severity of adverse effects can be increased when Piroxicam is
`combined with Aceclofenac.
`
`Approved
`
`Approved
`
`Approved
`
`Approved
`
`Acenocoumarol
`
`Piroxicam may increase the anticoagulant activities of Acenocoumarol.
`
`Approved
`
`Par Pharm., Inc.
`Exhibit 1059
`Page 004
`
`

`

`Acetovanillone
`
`The risk or severity of adverse effects can be increased when Piroxicam is
`combined with Acetovanillone.
`
`Investigational
`
`Showing 1 to 10 of 474 entries
`
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`
`1
`
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`
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`
`4
`
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`
`…
`
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`
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`
`Food Interactions
`
`Take with food. Avoid alcohol.
`
`References
`References
`
`Synthesis
`Reference
`
`Paul D. Weeks, “3-Hydroxy 2-methyl benzisothiazolines as intermediates in production of piroxicam.” U.S. Patent
`US4376204, issued April, 1982.
`
`
`US4376204
`
`General References Not Available
`
`External Links
`
`Resource
`
`KEGG Drug
`
`KEGG Compound
`
`PubChem Compound
`
`PubChem Substance
`
`ChEBI
`
`ChEMBL
`
`Therapeutic Targets Database
`
`DAP000181
`
`ATC Codes
`
`PharmGKB
`
`PA450985
`
`
`
`Drug Product Database
`
`1996
`
`
`
`RxList
`
`Drugs.com
`
`PDRhealth
`
`Wikipedia
`
`http://www.rxlist.com/cgi/generic/piroxicam.htm
`
`
`
`http://www.drugs.com/cdi/piroxicam.html
`
`
`
`http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/fel1173.shtml
`
`
`
`Piroxicam
`
`
`
`M02AA07
`M02AA — Antiinflammatory preparations, non-steroids for topical use
`M02A — TOPICAL PRODUCTS FOR JOINT AND MUSCULAR PAIN
`M02 — TOPICAL PRODUCTS FOR JOINT AND MUSCULAR PAIN
`M — MUSCULO-SKELETAL SYSTEM
`S01BC06
`S01BC — Antiinflammatory agents, non-steroids
`S01B — ANTIINFLAMMATORY AGENTS
`S01 — OPHTHALMOLOGICALS
`S — SENSORY ORGANS
`M01AC01
`M01AC — Oxicams
`M01A — ANTIINFLAMMATORY AND ANTIRHEUMATIC PRODUCTS, NON-STEROIDS
`M01 — ANTIINFLAMMATORY AND ANTIRHEUMATIC PRODUCTS
`M — MUSCULO-SKELETAL SYSTEM
`
`AHFS Codes
`
`28:08.04.92
`
`PDB Entries
`
`Not Available
`
`FDA label
`
`Download (74.3 KB)
`
`MSDS
`
`Download (73.3 KB)
`
`Clinical Trials
`Clinical Trials
`
`Clinical Trials
`
`
`
`Show 10
`
` entries
`
`Phase
`
`1, 2
`
`2
`
`Search
`
`Status
`
`Purpose
`
`Conditions
`
`Recruiting Treatment Renal Colic
`
`Completed Not
`Available
`
`Postcoital Contraception
`
`Count
`
`1
`
`1
`
`Link
`
` 
`
`D00127
`
`C01608
`
` 
`
`54676228
`
`46505225
`
`8249
`
`
`
`CHEMBL527
`
` 
`
`Par Pharm., Inc.
`Exhibit 1059
`Page 005
`
`

`

`2
`
`4
`
`4
`
`4
`
`4
`
`Completed Treatment Osteoarthritis of the Knees
`
`Completed Supportive
`Care
`
`Cytochrome P450 CYP2C9 Enzyme Deficiency /
`Impacted Third Molar Tooth / Other Surgical
`Procedures / Pain
`
`Completed Treatment Dysmenorrhea
`
`Completed Treatment Hypertensive
`
`Completed Treatment Primary Dysmenorrhea
`
`Not Available
`
`Completed Diagnostic Dermatitis, Photocontact
`
`Showing 1 to 8 of 8 entries
`
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`
`1
`
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`
`1
`
`1
`
`1
`
`1
`
`1
`
`1
`
`Pharmacoeconomics
`Pharmacoeconomics
`
`Manufacturers
`
`Packagers
`
`Akorn inc
`Pfizer laboratories div pfizer inc
`Egis pharmaceuticals
`Genpharm pharmaceuticals inc
`Ivax pharmaceuticals inc sub teva pharmaceuticals usa
`Mutual pharmaceutical co inc
`Mylan pharmaceuticals inc
`Nostrum laboratories inc
`Roxane laboratories inc
`Scs pharmaceuticals
`Teva pharmaceuticals usa inc
`Teva pharmaceuticals usa
`Watson laboratories inc
`
`Advanced Pharmaceutical Services Inc.
`Aidarex Pharmacuticals LLC
`Akorn Inc.
`Amerisource Health Services Corp.
`AQ Pharmaceuticals Inc.
`A-S Medication Solutions LLC
`Bryant Ranch Prepack
`Corepharma LLC
`Direct Dispensing Inc.
`Dispensing Solutions
`Diversified Healthcare Services Inc.
`Egis Pharmaceuticals Public Ltd. Co.
`Goldline Laboratories Inc.
`Group Health Cooperative
`H.J. Harkins Co. Inc.
`Innoviant Pharmacy Inc.
`Keltman Pharmaceuticals Inc.
`Lake Erie Medical and Surgical Supply
`Liberty Pharmaceuticals
`Major Pharmaceuticals
`Medisca Inc.
`Mepha Ltd.
`Murfreesboro Pharmaceutical Nursing Supply
`Mylan
`Nostrum Laboratories Inc.
`Novopharm Ltd.
`Nucare Pharmaceuticals Inc.
`Pack Pharmaceuticals
`Palmetto Pharmaceuticals Inc.
`PD-Rx Pharmaceuticals Inc.
`Pfizer Inc.
`Pharmaceutical Utilization Management Program VA Inc.
`Pharmedix
`Physicians Total Care Inc.
`Preferred Pharmaceuticals Inc.
`Prepackage Specialists
`Prepak Systems Inc.
`Prescription Dispensing Service Inc.
`
`Par Pharm., Inc.
`Exhibit 1059
`Page 006
`
`

`

`Qualitest
`Ranbaxy Laboratories
`Rebel Distributors Corp.
`Redpharm Drug
`Remedy Repack
`Sandhills Packaging Inc.
`Southwood Pharmaceuticals
`St Mary's Medical Park Pharmacy
`Teva Pharmaceutical Industries Ltd.
`UDL Laboratories
`United Research Laboratories Inc.
`Va Cmop Dallas
`Show 10
` entries
`
`Dosage forms
`
`Form
`
`Capsule
`
`Capsule
`
`Suppository
`
`Suppository
`
`Capsule
`
`Capsule
`
`Tablet
`
`Kit
`
`Search
`
`Route
`
`Oral
`
`Oral
`
`Rectal
`
`Rectal
`
`Oral
`
`Oral
`
`Oral
`
`Strength
`
`10 mg
`
`20 mg
`
`10 mg
`
`20 mg
`
`10 mg/1
`
`20 mg/1
`
`10 mg
`
`Prices
`
`Show 10
`
` entries
`
`Showing 1 to 8 of 8 entries
`
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`
`Unit description
`
`Piroxicam powder
`
`Akten 3.5% drops
`
`Feldene 20 mg capsule
`
`Feldene 10 mg capsule
`
`Piroxicam 20 mg capsule
`
`Pms-Piroxicam 20 mg Suppository
`
`Piroxicam 10 mg capsule
`
`Apo-Piroxicam 20 mg Capsule
`
`Novo-Pirocam 20 mg Capsule
`
`Nu-Pirox 20 mg Capsule
`
`Cost
`
`13.16USD
`
`7.5USD
`
`4.93USD
`
`2.82USD
`
`2.69USD
`
`1.82USD
`
`1.44USD
`
`0.75USD
`
`0.75USD
`
`0.75USD
`
`Unit
`
`g
`
`ml
`
`capsule
`
`capsule
`
`capsule
`
`suppository
`
`capsule
`
`capsule
`
`capsule
`
`capsule
`
`Showing 1 to 10 of 14 entries
`
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`
`1
`
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`
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`
`
`
` DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
`
`Patents
`
`Properties
`Properties
`
`State
`
`Experimental
`Properties
`
`Not Available
`
`Solid
`
`Property
`
`Value
`
`melting point
`
`198-200 °C
`
`Source
`
`PhysProp
`
`water solubility
`
`23 mg/L (at 22 °C)
`
`YALKOWSKY,SH & DANNENFELSER,RM (1992)
`
`logP
`
`3.06
`
`AVDEEF,A (1997)
`
`Par Pharm., Inc.
`Exhibit 1059
`Page 007
`
`

`

`Predicted
`Properties
`
`logS
`Property
`Caco2 permeability
`
`pKa
`
`Property
`
`Water Solubility
`
`logP
`
`logP
`
`logS
`
`pKa (Strongest Acidic)
`
`pKa (Strongest Basic)
`
`Physiological Charge
`
`Hydrogen Acceptor Count
`
`Hydrogen Donor Count
`
`Polar Surface Area
`
`Rotatable Bond Count
`
`Refractivity
`
`Polarizability
`
`Number of Rings
`
`Bioavailability
`
`Rule of Five
`
`Ghose Filter
`
`Veber's Rule
`
`MDDR-like Rule
`
`-4.16
`Value
`-4.45
`
`6.3
`
`ADME Research, USCD
`Source
`ADME Research, USCD
`
`SANGSTER (1994)
`
`Value
`
`0.143 mg/mL
`
`2.2
`
`0.6
`
`-3.4
`
`4.76
`
`3.79
`
`-1
`
`5
`
`2
`
`99.6 Å
`
`2
`
`2
`
`3
`87.04 m ·mol
`
`-1
`
`32.27 Å
`
`3
`
`3
`
`1
`
`Yes
`
`Yes
`
`Yes
`
`Yes
`
`Source
`
`ALOGPS
`
`ALOGPS
`
`ChemAxon
`
`ALOGPS
`
`ChemAxon
`
`ChemAxon
`
`ChemAxon
`
`ChemAxon
`
`ChemAxon
`
`ChemAxon
`
`ChemAxon
`
`ChemAxon
`
`ChemAxon
`
`ChemAxon
`
`ChemAxon
`
`ChemAxon
`
`ChemAxon
`
`ChemAxon
`
`ChemAxon
`
`Predicted ADMET
`features
`
`Property
`
`Human Intestinal Absorption
`
`Blood Brain Barrier
`
`Caco-2 permeable
`
`P-glycoprotein substrate
`
`P-glycoprotein inhibitor I
`
`P-glycoprotein inhibitor II
`
`Renal organic cation transporter
`
`CYP450 2C9 substrate
`
`CYP450 2D6 substrate
`
`CYP450 3A4 substrate
`
`CYP450 1A2 substrate
`
`CYP450 2C9 inhibitor
`
`CYP450 2D6 inhibitor
`
`CYP450 2C19 inhibitor
`
`CYP450 3A4 inhibitor
`
`Value
`
`+
`
`-
`
`+
`
`Substrate
`
`Non-inhibitor
`
`Non-inhibitor
`
`Non-inhibitor
`
`Substrate
`
`Non-substrate
`
`Non-substrate
`
`Non-inhibitor
`
`Inhibitor
`
`Non-inhibitor
`
`Non-inhibitor
`
`Non-inhibitor
`
`CYP450 inhibitory promiscuity
`
`Low CYP Inhibitory Promiscuity
`
`Ames test
`
`Carcinogenicity
`
`Biodegradation
`
`Rat acute toxicity
`
`hERG inhibition (predictor I)
`
`hERG inhibition (predictor II)
`
`Non AMES toxic
`
`Non-carcinogens
`
`Not ready biodegradable
`
`3.1545 LD50, mol/kg
`
`Weak inhibitor
`
`Non-inhibitor
`
`Probability
`
`0.9898
`
`0.9659
`
`0.8867
`
`0.5786
`
`0.7285
`
`0.7453
`
`0.9437
`
`0.6437
`
`0.9116
`
`0.7356
`
`0.9045
`
`0.9086
`
`0.9231
`
`0.9025
`
`0.8789
`
`0.8709
`
`0.8767
`
`0.7612
`
`0.923
`
`Not applicable
`
`0.9589
`
`0.8311
`
`Par Pharm., Inc.
`Exhibit 1059
`Page 008
`
`

`

`
`
` ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. ( 23092397
`
`
`
`)
`
`Spectra
`Spectra
`
`Mass Spec (NIST)
`
`Not Available
`
`Spectra
`
`Spectrum Type
`
`Description
`
`Predicted LC-MS/MS
`
`Predicted LC-MS/MS Spectrum - 10V, Positive
`
`Predicted LC-MS/MS
`
`Predicted LC-MS/MS Spectrum - 20V, Positive
`
`Predicted LC-MS/MS
`
`Predicted LC-MS/MS Spectrum - 40V, Positive
`
`Predicted LC-MS/MS
`
`Predicted LC-MS/MS Spectrum - 10V, Negative
`
`Predicted LC-MS/MS
`
`Predicted LC-MS/MS Spectrum - 20V, Negative
`
`Predicted LC-MS/MS
`
`Predicted LC-MS/MS Spectrum - 40V, Negative
`
`Splash Key
`
`Not Available
`
`Not Available
`
`Not Available
`
`Not Available
`
`Not Available
`
`Not Available
`
`Taxonomy
`Taxonomy
`
`Description
`
`This compound belongs to the class of organic compounds known as benzothiazines. These are organic compounds
`containing a benzene fused to a thiazine ring (a six-membered ring with four carbon atoms, one nitrogen atom and one
`sulfur atom).
`
`Kingdom
`
`Organic compounds
`
`
`
`Super Class
`
`Organoheterocyclic compounds
`
`
`
`Class
`
`Benzothiazines
`
`
`
`Sub Class
`
`Not Available
`
`Direct Parent
`
`Benzothiazines
`
`
`
`Alternative Parents
`
`Substituents
`
`
`
`
`
`Alpha amino acids and derivatives
`
`Pyridines and derivatives
`
`Organosulfonamides
`
`1,2-thiazines
`
`Benzenoids
`
`Imidolactams
`
`Heteroaromatic compounds
`Secondary carboxylic acid amides
`
`Azacyclic compounds
`
`Carboximidic acids
`Hydrocarbon derivatives
`
`Carbonyl compounds
`
`Organic oxides
`
`Organic zwitterions
`
`Organonitrogen compounds
`
`Organopnictogen compounds
`
`
`
`Alpha-amino acid or derivatives
`Benzothiazine
`Ortho-thiazine
`Pyridine
`Organosulfonic acid amide
`Benzenoid
`Imidolactam
`Organic sulfonic acid or derivatives
`Organosulfonic acid or derivatives
`Heteroaromatic compound
`Secondary carboxylic acid amide
`Carboxylic acid derivative
`Carboximidic acid
`Azacycle
`Hydrocarbon derivative
`Organic oxygen compound
`Organic nitrogen compound
`Organic oxide
`Organooxygen compound
`Organonitrogen compound
`Carbonyl group
`Organopnictogen compound
`
`Par Pharm., Inc.
`Exhibit 1059
`Page 009
`
`

`

`Organic zwitterion
`Aromatic heteropolycyclic compound
`Aromatic heteropolycyclic compounds
`
`monocarboxylic acid amide (CHEBI:8249
`
`pyridines (CHEBI:8249
`)
`benzothiazine (CHEBI:8249
`
`
`
`)
`
`
`
`)
`
`Molecular
`Framework
`
`External
`Descriptors
`
`Targets
`
`1. Prostaglandin G/H synthase 2
`
`
`
` Details
`
`Kind
`Protein
`Organism
`Human
`Pharmacological action
`yes
`Actions
`
`inhibitor
`
`General Function:
`Prostaglandin-endoperoxide synthase activity
`Specific Function:
`Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Constitutively expressed in some tissues
`in physiological conditions, such as the endothelium, kidney and brain, and in pathological conditions, such as in cancer. PTGS2 is
`responsible for production of inflammatory prostaglandins. Up-regulation of PTGS2 is also associated with increased cell adhesion, p...
`Gene Name:
`PTGS2
`Uniprot ID:
`
`P35354
`Molecular Weight:
`68995.625 Da
`
`References
`
`1. Blanco FJ, Guitian R, Moreno J, de Toro FJ, Galdo F: Effect of antiinflammatory drugs on COX-1 and COX-2 activity in human articular
`
`chondrocytes. J Rheumatol. 1999 Jun;26(6):1366-73. [PubMed:10381057
`]
`2. Bugajski J, Glod R, Gadek-Michalska A, Bugajski AJ: Involvement of constitutive (COX-1) and inducible cyclooxygenase (COX-2) in the
`
`adrenergic-induced ACTH and corticosterone secretion. J Physiol Pharmacol. 2001 Dec;52(4 Pt 2):795-809. [PubMed:11785774
`]
`3. Fackovcova D, Kristova V, Kriska M: Renal damage induced by the treatment with non-opioid analgesics--theoretical assumption or clinical
`
`significance. Bratisl Lek Listy. 2000;101(8):417-22. [PubMed:11153163
`]
`4. Raju J, Bird RP: Differential modulation of transforming growth factor-betas and cyclooxygenases in the platelet lysates of male F344 rats by
`
`dietary lipids and piroxicam. Mol Cell Biochem. 2002 Feb;231(1-2):139-46. [PubMed:11952155
`]
`5. Veiga AP, Duarte ID, Avila MN, da Motta PG, Tatsuo MA, Francischi JN: Prevention by celecoxib of secondary hyperalgesia induced by
`
`formalin in rats. Life Sci. 2004 Oct 22;75(23):2807-17. [PubMed:15464832
`]
`
`6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352
`
`]
`
`2. Prostaglandin G/H synthase 1
`
`
`
` Details
`
`Kind
`Protein
`Organism
`Human
`Pharmacological action
`unknown
`Actions
`
`inhibitor
`
`General Function:
`Prostaglandin-endoperoxide synthase activity
`Specific Function:
`Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Involved in the constitutive production
`of prostanoids in particular in the stomach and platelets. In gastric epithelial cells, it is a key step in the generation of prostaglandins,
`such as prostaglandin E2 (PGE2), which plays an important role in cytoprotection. In platelets, it is involved in the gener...
`Gene Name:
`
`Par Pharm., Inc.
`Exhibit 1059
`Page 010
`
`

`

`PTGS1
`Uniprot ID:
`
`P23219
`Molecular Weight:
`68685.82 Da
`
`References
`
`1. Blanco FJ, Guitian R, Moreno J, de Toro FJ, Galdo F: Effect of antiinflammatory drugs on COX-1 and COX-2 activity in human articular
`
`chondrocytes. J Rheumatol. 1999 Jun;26(6):1366-73. [PubMed:10381057
`]
`2. Bugajski J, Glod R, Gadek-Michalska A, Bugajski AJ: Involvement of constitutive (COX-1) and inducible cyclooxygenase (COX-2) in the
`
`adrenergic-induced ACTH and corticosterone secretion. J Physiol Pharmacol. 2001 Dec;52(4 Pt 2):795-809. [PubMed:11785774
`]
`3. Fackovcova D, Kristova V, Kriska M: Renal damage induced by the treatment with non-opioid analgesics--theoretical assumption or clinical
`
`significance. Bratisl Lek Listy. 2000;101(8):417-22. [PubMed:11153163
`]
`4. Raju J, Bird RP: Differential modulation of transforming growth factor-betas and cyclooxygenases in the platelet lysates of male F344 rats by
`
`dietary lipids and piroxicam. Mol Cell Biochem. 2002 Feb;231(1-2):139-46. [PubMed:11952155
`]
`5. Veiga AP, Duarte ID, Avila MN, da Motta PG, Tatsuo MA, Francischi JN: Prevention by celecoxib of secondary hyperalgesia induced by
`
`formalin in rats. Life Sci. 2004 Oct 22;75(23):2807-17. [PubMed:15464832
`]
`
`Enzymes
`
`1. Cytochrome P450 2C9
`
`Kind
`Protein
`Organism
`Human
`Pharmacological action
`unknown
`Actions
`
`substrate
`
`inhibitor
`
`
`
` Details
`
`General Function:
`Steroid hydroxylase activity
`Specific Function:
`Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-
`dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and
`xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac,
`phenyto...
`Gene Name:
`CYP2C9
`Uniprot ID:
`
`P11712
`Molecular Weight:
`55627.365 Da
`
`References
`
`1. Zhou SF, Zhou ZW, Yang LP, Cai JP: 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. Epub 2009 Sep 1. [PubMed:19515014
`]
`2. Pelkonen O, Maenpaa J, Taavitsainen P, Rautio A, Raunio H: Inhibition and induction of human cytochrome P450 (CYP) enzymes. Xenobiotica.
`
`1998 Dec;28(12):1203-53. [PubMed:9890159
`]
`3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a
`comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010
`
`Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256
`]
`4. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
`
`2. Cytochrome P450 2C8
`
`Kind
`Protein
`Organism
`Human
`Pharmacological action
`unknown
`
`
`
` Details
`
`Par Pharm., Inc.
`Exhibit 1059
`Page 011
`
`

`

`Actions
`
`substrate
`
`inhibitor
`
`General Function:
`Steroid hydroxylase activity
`Specific Function:
`Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-
`dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and
`xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal
`enzyme...
`Gene Name:
`CYP2C8
`Uniprot ID:
`
`P10632
`Molecular Weight:
`55824.275 Da
`
`References
`
`1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a
`comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010
`
`Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256
`]
`
`Carriers
`
`1. Serum albumin
`
`Kind
`Protein
`Organism
`Human
`Pharmacological action
`unknown
`
`
`
` Details
`
`General Function:
`Toxic substance binding
`Specific Function:
`Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin
`and drugs. Its main function is the regulation of the colloidal osmotic pressure of blood. Major zinc transporter in plasma, typically binds
`about 80% of all plasma zinc.
`Gene Name:
`ALB
`Uniprot ID:
`
`P02768
`Molecular Weight:
`69365.94 Da
`
`References
`
`1. Bertucci C, Wainer IW: Improved chromatographic performance of a modified human albumin based stationary phase. Chirality.
`
`1997;9(4):335-40. [PubMed:9275312
`]
`
`Transporters
`
`1. Solute carrier family 22 member 6
`
`
`
` Details
`
`Kind
`Protein
`Organism
`Human
`Pharmacological action
`unknown
`
`Par Pharm., Inc.
`Exhibit 1059
`Page 012
`
`

`

`Actions
`
`inhibitor
`
`General Function:
`Sodium-independent organic anion transmembrane transporter activity
`Specific Function:
`Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake
`of one molecule of organic anion is coupled with an efflux of one molecule of endogenous dicarboxylic acid (glutarate, ketoglutarate,
`etc). Mediates the sodium-independent uptake of 2,3-dimercapto-1-propanesulfonic acid (DMPS) (By similarity). Mediates the sodium-
`in...
`Gene Name:
`SLC22A6
`Uniprot ID:
`
`Q4U2R8
`Molecular Weight:
`61815.78 Da
`
`References
`
`1. Mulato AS, Ho ES, Cihlar T: Nonsteroidal anti-inflammatory drugs efficiently reduce the transport and cytotoxicity of adefovir mediated by
`
`the human renal organic anion transporter 1. J Pharmacol Exp Ther. 2000 Oct;295(1):10-5. [PubMed:10991954
`]
`2. Jung KY, Takeda M, Kim DK, Tojo A, Narikawa S, Yoo BS, Hosoyamada M, Cha SH, Sekine T, Endou H: Characterization of ochratoxin A
`
`transport by human organic anion transporters. Life Sci. 2001 Sep 21;69(18):2123-35. [PubMed:11669456
`]
`3. Takeda M, Khamdang S, Narikawa S, Kimura H, Hosoyamada M, Cha SH, Sekine T, Endou H: Characterization of methotrexate transport and
`
`its drug interactions with human organic anion transporters. J Pharmacol Exp Ther. 2002 Aug;302(2):666-71. [PubMed:12130730
`]
`4. Apiwattanakul N, Sekine T, Chairoungdua A, Kanai Y, Nakajima N, Sophasan S, Endou H: Transport properties of nonsteroidal anti-
`inflammatory drugs by organic anion transporter 1 expressed in Xenopus laevis oocytes. Mol Pharmacol. 1999 May;55(5):847-54.
`
`[PubMed:10220563
`]
`5. Tsuda M, Sekine T, Takeda M, Cha SH, Kanai Y, Kimura M, Endou H: Transport of ochratoxin A by renal multispecific organic anion transporter
`
`1. J Pharmacol Exp Ther. 1999 Jun;289(3):1301-5. [PubMed:10336520
`]
`
`2. Solute carrier family 22 member 8
`
`
`
` Details
`
`Kind
`Protein
`Organism
`Human
`Pharmacological action
`unknown
`Actions
`
`inhibitor
`
`General Function:
`Sodium-independent organic anion transmembrane transporter activity
`Specific Function:
`Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and
`kidney. Involved in the transport basolateral of steviol, fexofenadine. Transports benzylpenicillin (PCG), estrone-3-sulfate (E1S),
`cimetidine (CMD), 2,4-dichloro-phenoxyacetate (2,4-D), p-amino-hippurate (PAH), acyclovir (ACV) and ochratoxin (OTA).
`Gene Name:
`SLC22A8
`Uniprot ID:
`
`Q8TCC7
`Molecular Weight:
`59855.585 Da
`
`References
`
`1. Jung KY, Takeda M, Kim DK, Tojo A, Narikawa S, Yoo BS, Hosoyamada M, Cha SH, Sekine T, Endou H: Characterization of ochratoxin A
`
`transport by human organic anion transporters. Life Sci. 2001 Sep 21;69(18):2123-35. [PubMed:11669456
`]
`2. Takeda M, Khamdang S, Narikawa S, Kimura H, Hosoyamada M, Cha SH, Sekine T, Endou H: Characterization of methotrexate transport and
`its drug interactions with human organic anion transporters. J Pharmacol Exp Ther. 2002 Aug;302(2):666-71. [PubMed:12130730
`]
`3. Kusuhara H, Sekine T, Utsunomiya-Tate N, Tsuda M, Kojima R, Cha SH, Sugiyama Y, Kanai Y, Endou H: Molecular cloning and characterization
`of a new multispecific organic anion transporter from rat brain. J Biol Chem. 1999 May 7;274(19):13675-80. [PubMed:10224140
`]
`
` 
`
`3. Solute carrier family 22 member 11
`
`
`
` Details
`
`Par Pharm., Inc.
`Exhibit 1059
`Page 013
`
`

`

`Kind
`Protein
`Organism
`Human
`Pharmacological action
`unknown
`Actions
`
`inhibitor
`
`General Function:
`Sodium-independent organic anion transmembrane transporter activity
`Specific Function:
`Mediates saturable uptake of estrone sulfate, dehydroepiandrosterone sulfate and related compounds.
`Gene Name:
`SLC22A11
`Uniprot ID:
`
`Q9NSA0
`Molecular Weight:
`59970.945 Da
`
`References
`
`1. Babu E, Takeda M, Narikawa S, Kobayashi Y, Enomoto A, Tojo A, Cha SH, Sekine T, Sakthisekaran D, Endou H: Role of human organic anion
`
`transporter 4 in the transport of ochratoxin A. Biochim Biophys Acta. 2002 Jun 12;1590(1-3):64-75. [PubMed:12063169
`]
`2. Takeda M, Khamdang S, Narikawa S, Kimura H, Hosoyamada M, Cha SH, Sekine T, Endou H: Characterization of methotrexate transport and
`
`its drug interactions with human organic anion transporters. J Pharmacol Exp Ther. 2002 Aug;302(2):666-71. [PubMed:12130730
`]
`
`Comments
`
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`Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23
`
`ABOUT US
`
`About DrugBank
`Wishart Research Group
`
`Par Pharm., Inc.
`Exhibit 1059
`Page 014
`
`

`

`SUPPORT
`
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`Help
`
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`
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`
`This project is supported by the Canadian Institutes of Health Research (award #111062), Alberta Innovates - Health Solutions, and by The Metabolomics Innovation
`Centre (TMIC), a nationally-funded research and core facility that supports a wide range of cutting-edge metabolomic studies. TMIC is funded by Genome Alberta,
`Genome British Columbia, and Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $900 million in funding from the
`federal government. Maintenance, support, and commercial licensing is provided by OMx Personal Health Analytics, Inc.
`
`Par Pharm., Inc.
`Exhibit 1059
`Page 015
`
`