6/1/2018
`
`Latanoprost - DrugBank
`
`Latanoprost
`
`Targets (1)
`
`Transporters (2)
`
`Biointeractions (2)
`
`IDENTIFICATION
`
`Name
`
`Latanoprost
`
`Accession Number
`
`DB00654 (APRD01065)
`
`Type
`
`Small Molecule
`
`Groups
`
`Approved, Investigational
`
`Description
`
`Latanoprost ophthalmic solution is a topical medication used for controlling the progression
`of glaucoma or ocular hypertension, by reducing intraocular pressure. It is a prostaglandin
`analogue that works by increasing the outflow of aqueous fluid from the eyes.
`
`It is also known by the brand name of Xalatan manufactured by Pfizer.
`
`Structure
`
`HO
`
`HO
`
`OH
`
`O
`
`CH3
`
`O
`
`CH3
`
`https://www.drugbank.ca/drugs/DB00654
`
`1/24
`
`Micro Labs Exhibit 1052
`Micro Labs v. Santen Pharm. and Asahi Glass
`IPR2017-01434
`
`
`
`Latanoprost - DrugBank
`
`Latanoprost
`
`Targets (1)
`
`Transporters (2)
`
`Biointeractions (2)
`
`IDENTIFICATION
`
`Name
`
`Latanoprost
`
`Accession Number
`
`DB00654 (APRD01065)
`
`Type
`
`Small Molecule
`
`Groups
`
`Approved, Investigational
`
`Description
`
`Latanoprost ophthalmic solution is a topical medication used for controlling the progression
`of glaucoma or ocular hypertension, by reducing intraocular pressure. It is a prostaglandin
`analogue that works by increasing the outflow of aqueous fluid from the eyes.
`
`It is also known by the brand name of Xalatan manufactured by Pfizer.
`
`Structure
`
`HO
`
`HO
`
`OH
`
`O
`
`CH3
`
`O
`
`CH3
`
`https://www.drugbank.ca/drugs/DB00654
`
`1/24
`
`Micro Labs Exhibit 1052
`Micro Labs v. Santen Pharm. and Asahi Glass
`IPR2017-01434
`
`
`
`6/1/2018
`
`Latanoprost - DrugBank
`
`3D
`
` Similar Structures
`
`Synonyms
`
`Isopropyl (Z)-7-((1R,2R,3R,5S)-3,5-dihydroxy-2-((3R)-3-hydroxy-5-phenylpentyl)cyclopentyl)-5-heptenoate
`
`Latanoprost
`
`Latanoprostum
`
`PhXA 41
`
`Propan-2-yl (5Z)-7-{(1R,2R,3R,5S)-3,5-dihydroxy-2-[(3R)-3-hydroxy-5-phenylpentyl]cyclopentyl}hept-5-enoate
`
`External IDs
`
`PHXA 41 / PHXA-41 / PHXA41 / T-2345 / T2345 / XA 41 / XA-41 / XA41
`
`Prescription Products
`
`Search
`
`NAME
`+
`
`Act Latanoprost
`
`Solution
`
`50 mcg
`
`↑↓ DOSAGE ↑↓ STRENGTH ↑↓ ROUTE ↑↓ LABELLER
`
`↑↓
`
`MARKETING
`START
`
`↓
`
`2011-10-13
`
`Not applicable
`
`Not applicable
`
`Ophthalmic Actavis Pharma
`Company
`
`Ophthalmic Bausch & Lomb
`Inc
`
`Ophthalmic Laboratoire
`Riva Inc
`
`Bl Latanoprost
`
`Solution
`
`50 mcg
`
`Latanoprost
`
`Solution
`
`50 mcg
`
`Monoprost
`
`Solution
`
`50 mcg
`
`Sandoz Latanoprost
`
`Solution
`
`50 mcg
`
`+
`
`+
`
`+
`
`+
`
`+
`
`+
`
`+
`
`+
`
`Latanoprost
`Ophthalmic Solution
`
`Solution
`
`50 mcg
`
`Ophthalmic Sandoz Canada
`Incorporated
`
`Not applicable
`
`Ophthalmic Laboratoires
`Thea
`
`2018-01-03
`
`Ophthalmic Sandoz Canada
`Incorporated
`
`2011-12-06
`
`Ophthalmic Dispensing
`Solutions, Inc.
`
`Ophthalmic Pharmacia &
`Upjohn Inc
`
`1995-03-20
`
`1995-03-20
`
`Solution
`
`50 ug/mL
`
`Solution
`
`50 ug/mL
`
`Xalatan
`
`Xalatan
`
`Xalatan
`
`Solution
`
`50 mcg
`
`Ophthalmic Pfizer
`
`1997-07-28
`
`Showing 1 to 9 of 9 entries
`
`https://www.drugbank.ca/drugs/DB00654
`
`2/24
`
`Micro Labs Exhibit 1052-2
`
`
`
`6/1/2018
`
`Latanoprost - DrugBank
`‹
`›
`
`Generic Prescription Products
`
`Search
`
`↑↓ DOSAGE ↑↓ STRENGTH ↑↓ ROUTE ↑↓ LABELLER
`
`MARKETING
`START
`
`↓
`
`↑↓
`
`NAME
`+
`
`Apo-
`latanoprost
`
`Gd-
`latanoprost
`
`Jamp-
`latanoprost
`
`Latanoprost
`
`Latanoprost
`
`Latanoprost
`
`Latanoprost
`
`+
`
`+
`
`+
`
`+
`
`+
`
`+
`
`+
`+
`
`+
`
`Solution
`
`50 mcg
`
`Ophthalmic Apotex Corporation
`
`2011-10-03
`
`Solution
`
`50 mcg
`
`Solution
`
`50 mcg
`
`Ophthalmic Genmed A Division Of
`Pfizer Canada Inc
`
`2011-10-03
`
`Ophthalmic Jamp Pharma
`Corporation
`
`Not applicable
`
`Solution /
`drops
`
`Solution /
`drops
`
`Solution /
`drops
`
`Solution /
`drops
`
`50 ug/mL
`
`Ophthalmic Mwi
`
`2015-04-08
`
`50 ug/mL
`
`Ophthalmic Rebel Distributors
`
`2011-03-22
`
`50 ug/mL
`
`Ophthalmic A S Medication Solutions 2012-07-01
`
`50 ug/mL
`
`Ophthalmic Directrx
`
`2017-03-27
`
`2016-09-01
`
`2011-01-07
`
`Latanoprost
`
`Solution
`
`50 ug/mL
`
`Ophthalmic Fdc Limited
`
`Latanoprost
`
`Solution
`
`50 ug/mL
`
`Ophthalmic Sandoz
`
`Latanoprost
`
`Solution
`
`50 ug/mL
`
`Ophthalmic American Regent
`
`2011-08-02
`
`Showing 1 to 10 of 25 entries
`
`‹
`
`›
`
`Mixture Products
`
`Search
`
`NAME
`+
`
`Act
`Latanoprost/timolol
`https://www.drugbank.ca/drugs/DB00654
`
`↑↓
`
`INGREDIENTS
`
`DOSAGE ↑↓ ROUTE ↑↓ LABELLER
`
`↑↓
`
`Latanoprost
`(50 mcg) +
`
`Solution
`
`Ophthalmic Actavis Pharma
`Company
`
`MARKETING
`START
`
`↓
`
`2015-09-29
`
`3/24
`
`Micro Labs Exhibit 1052-3
`
`
`
`6/1/2018
`
`Latanoprost/timolol
`
`+
`
`Apo-latanoprost-
`timop
`
`+
`
`+
`
`+
`
`+
`
`+
`
`+
`
`+
`
`+
`
`Gd-
`latanoprost/timolol
`
`Jamp-
`latanoprost/timolol
`
`Med-latanoprost-
`timolol
`
`Mint-
`latanoprost/timolol
`
`Mylan-
`latanoprost/timolol
`
`PMS-latanoprost-
`timolol
`
`Riva-
`latanoprost/timolol
`
`Sandoz
`Latanoprost/timolol
`
`(50 mcg) +
`Timolol (5
`mg)
`
`Latanoprost
`(50 mcg) +
`Timolol (5
`mg)
`
`INGREDIENTS
`
`Latanoprost
`(50 mcg) +
`Timolol (5
`mg)
`
`Latanoprost
`(50 mcg) +
`Timolol (5
`mg)
`
`Latanoprost
`(50 mcg) +
`Timolol (5
`mg)
`
`Latanoprost
`(50 mcg) +
`Timolol (5
`mg)
`
`Latanoprost
`(50 mcg) +
`Timolol (5.0
`mg)
`
`Latanoprost
`(50 mcg) +
`Timolol (5
`mg)
`
`Latanoprost
`(50 mcg) +
`Timolol (5
`mg)
`
`Latanoprost
`(50 mcg) +
`Timolol (5
`mg)
`
`Latanoprost - DrugBank
`
`Company
`
`Solution
`
`Ophthalmic Apotex
`Corporation
`
`2014-07-02
`
`Solution
`
`Solution
`
`Ophthalmic Genmed A
`Division Of
`Pfizer Canada
`Inc
`
`Ophthalmic Jamp Pharma
`Corporation
`
`2013-05-01
`
`Not applicable
`
`Solution
`
`Ophthalmic Generic Medical
`Partners Inc
`
`Not applicable
`
`Solution
`
`Ophthalmic Mint
`Pharmaceuticals
`Inc
`
`Not applicable
`
`Solution
`
`Ophthalmic Mylan
`Pharmaceuticals
`
`Not applicable
`
`Solution
`
`Ophthalmic Pharmascience
`Inc
`
`Not applicable
`
`Solution
`
`Ophthalmic Laboratoire Riva
`Inc
`
`2017-01-03
`
`Solution
`
`Ophthalmic Sandoz Canada
`Incorporated
`
`2013-03-04
`
`https://www.drugbank.ca/drugs/DB00654
`
`4/24
`
`Micro Labs Exhibit 1052-4
`
`
`
`6/1/2018
`
`Latanoprost - DrugBank
`
`Showing 1 to 10 of 12 entries
`
`‹
`
`›
`
`Unapproved/Other Products
`
`Search
`
`↑↓
`
`INGREDIENTS
`
`DOSAGE ↑↓ ROUTE ↑↓ LABELLER ↑↓
`
`NAME
`+
`
`Latanoprost
`PF
`
`Latanoprost (.05 mg/mL) Solution /
`drops
`
`Ophthalmic Imprimis Rx
`Nj
`
`MARKETING
`START
`
`↓
`
`2018-01-01
`
`+
`
`Tim-Brim-
`Dor-Lat
`
`+
`
`Tim-Dor-Lat
`
`Latanoprost (.05 mg/mL)
`+ Brimonidine tartrate
`(1.5 mg/mL) +
`Dorzolamide
`Hydrochloride (20
`mg/mL) + Timolol
`maleate (5 mg/mL)
`
`Latanoprost (.05 mg/mL)
`+ Dorzolamide
`Hydrochloride (20
`mg/mL) + Timolol
`maleate (5 mg/mL)
`
`+
`
`Tim-Lat -PF
`
`INGREDIENTS
`
`Latanoprost (.05 mg/mL)
`+ Timolol maleate (5
`mg/mL)
`
`Showing 1 to 4 of 4 entries
`
`Solution /
`drops
`
`Ophthalmic Imprimis Rx
`Nj
`
`2018-01-01
`
`Solution /
`drops
`
`Ophthalmic Imprimis Rx
`Nj
`
`2018-01-01
`
`Solution /
`drops
`
`Ophthalmic Imprimis Rx
`Nj
`
`2018-01-01
`
`‹
`
`›
`
`International/Other Brands
`
`Arulatan (Dr. Gerhard Mann) / Gaap (Sophia) / Gaap O(cid:813)eno (Sophia) / Gaax (Chile) / Glaucogesic (Atlas)
`/ Glaumax (Kevelt) / Glauprost (Arrow) / Hysite (Pfizer) / Iopize (SIFI) / Ioprost (FDC) / Ioptame (Cadila)
`/ Klonaprost (Klonal) / Lanoprost (Synpac-Kingdom) / Lanotan (Kuk Je) / Laprost (O(cid:813)almi) /
`Latacris (Sun-Farm) / Latalux (Jelfa) / Latan-Ophtal (Winzer) / Lataneau (Alapis Pharma) / Xalatan
`
`https://www.drugbank.ca/drugs/DB00654
`
`5/24
`
`Micro Labs Exhibit 1052-5
`
`
`
`6/1/2018
`
`Categories
`
`Antiglaucoma Preparations and Miotics
`
`Latanoprost - DrugBank
`
`Antihypertensive Agents
`
`Autacoids
`
`Biological Factors
`
`Cardiovascular Agents
`
`Eicosanoids
`
`Fatty Acids
`
`Fatty Acids, Unsaturated
`
`Inflammation Mediators
`
`Intraocular Pressure, drug effects
`
`Lipids
`
`Neuroprotective Agents
`
`Ophthalmologicals
`
`Prostaglandins
`
`Prostaglandins, Synthetic
`
`Sensory Organs
`
`UNII
`
`6Z5B6HVF6O
`
`CAS number
`
`130209-82-4
`
`Weight
`
`Average: 432.5928
`Monoisotopic: 432.28757439
`
`Chemical Formula
`
`C H O
`26 40 5
`
`I ChI K
`https://www.drugbank.ca/drugs/DB00654
`
`6/24
`
`Micro Labs Exhibit 1052-6
`
`
`
`6/1/2018
`InChI Key
`
`GGXICVAJURFBLW-CEYXHVGTSA-N
`
`Latanoprost - DrugBank
`
`InChI
`
`InChI=1S/C26H40O5/c1-19(2)31-26(30)13-9-4-3-8-12-22-23(25(29)18-24(22)28)17-16-21(27)15-14-20-10-6-5-7-11-20/h3,5-8,10
`-11,19,21-25,27-29H,4,9,12-18H2,1-2H3/b8-3-/t21-,22+,23+,24-,25+/m0/s1
`
`IUPAC Name
`
`propan-2-yl (5Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(3R)-3-hydroxy-5-phenylpentyl]cyclopentyl]hept-5-enoate
`
`SMILES
`
`CC(C)OC(=O)CCC\C=C/C[C@H]1[C@@H](O)C[C@@H](O)[C@@H]1CC[C@@H](O)CCC1=CC=CC=C1
`
`PHARMACOLOGY
`
`Indication
`
`For the reduction of elevated intraocular pressure in patients with open-angle glaucoma or
`ocular hypertension.
`
`Associated Conditions
`
`Ocular Hypertension
`
`Open-angle Glaucoma (OAG)
`
`Pharmacodynamics
`
`Latanoprost is an isopropyl ester prodrug which is inactive but which becomes active a(cid:813)er
`hydrolysis to the acid from. Latanoprost opthalmic solution is a topical medication used for
`controlling the progression of glaucoma or ocular hypertension, by reducing intraocular
`pressure. It is a prostaglandin analogue that works by increasing the outflow of aqueous fluid
`from the eyes.
`
`Mechanism of action
`
`Latanoprost is a prostaglandin F2a analogue. Specifically, Latanoprost is a prostanoid selective
`FP receptor agonist that is believed to reduce the intraocular pressure (IOP) by increasing the
`outflow of aqueous humor. Studies in animals and man suggest that the main mechanism of
`action is increased uveoscleral outflow. Elevated IOP represents a major risk factor for
`glaucomatous field loss. The higher the level of IOP, the greater the likelihood of optic nerve
`damage and visual field loss.
`https://www.drugbank.ca/drugs/DB00654
`
`7/24
`
`Micro Labs Exhibit 1052-7
`
`
`
`6/1/2018
`
`Latanoprost - DrugBank
`
`A Prostaglandin F2-alpha receptor
`
`agonist
`
`Human
`
`Absorption
`
`Latanoprost is well absorbed through the cornea where the isopropyl ester prodrug is
`hydrolyzed to the acid form. Peak concentration is reached 2 hrs a(cid:813)er topical administration.
`
`Volume of distribution
`
`Not Available
`
`Protein binding
`
`Not Available
`
`Metabolism
`
`Primarily hepatic (none except hydrolysis in the eye). Latanoprost is an isopropyl ester
`prodrug. It is hydrolyzed by esterases in the cornea to latanoprost acid, which is biologically
`active. The portion of the latanoprost acid that reaches the systemic circulation is
`metabolized primarily by the liver to 1,2-dinor and 1,2,3,4-tetranor metabolites by fatty acid
`beta-oxidation.
`
`Route of elimination
`
`Not Available
`
`Half life
`
`17 minutes
`
`Clearance
`
`7 mL/min/kg
`
`Toxicity
`
`Symptoms of overdose include bloodshot eyes and eye irritation.
`
`Affected organisms
`https://www.drugbank.ca/drugs/DB00654
`
`8/24
`
`Micro Labs Exhibit 1052-8
`
`
`
`6/1/2018
`
`Latanoprost - DrugBank
`
`Humans and other mammals
`
`Pathways
`
`Not Available
`
`Pharmacogenomic Effects/ADRs
`
`Not Available
`
`INTERACTIONS
`
`Drug Interactions
`
`Search
`
`DRUG
`
`(4R)-limonene
`
`↑↓ DRUG GROUP ↑↓
`↓ INTERACTION
`The therapeutic efficacy of Latanoprost can be decreased
`Investigational
`when used in combination with (4R)-limonene.
`
`7,8-Dichloro-1,2,3,4-
`tetrahydroisoquinoline
`
`7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline may increase
`the hypotensive activities of Latanoprost.
`
`Experimental
`
`Acebutolol
`
`Aceclofenac
`
`Acemetacin
`
`Latanoprost may increase the hypotensive activities of
`Acebutolol.
`
`Approved,
`Investigational
`
`The therapeutic efficacy of Latanoprost can be decreased
`when used in combination with Aceclofenac.
`
`Approved,
`Investigational
`
`The therapeutic efficacy of Latanoprost can be decreased
`when used in combination with Acemetacin.
`
`Approved,
`Experimental,
`Investigational
`
`Acetylsalicylic acid
`
`The therapeutic efficacy of Latanoprost can be decreased
`when used in combination with Acetylsalicylic acid.
`
`Approved, Vet
`Approved
`
`Adapalene
`
`Alclofenac
`
`Alfuzosin
`
`Aliskiren
`
`The therapeutic efficacy of Latanoprost can be decreased
`when used in combination with Adapalene.
`
`Approved
`
`The therapeutic efficacy of Latanoprost can be decreased
`when used in combination with Alclofenac.
`
`Approved,
`Withdrawn
`
`Alfuzosin may increase the hypotensive activities of
`Latanoprost.
`
`Latanoprost may increase the hypotensive activities of
`Aliskiren.
`
`Approved,
`Investigational
`
`Approved,
`Investigational
`
`Sh
`i
`1 t 10 f 351
`https://www.drugbank.ca/drugs/DB00654
`
`t i
`
`9/24
`
`Micro Labs Exhibit 1052-9
`
`
`
`6/1/2018
`Showing 1 to 10 of 351 entries
`
`Latanoprost - DrugBank
`
`‹
`
`›
`
`Food Interactions
`
`Not Available
`
`REFERENCES
`
`Synthesis Reference
`
`Arie Gutman, "Process for the preparation of latanoprost." U.S. Patent US20030149294, issued
`August 07, 2003.
`US20030149294
`
`General References
`
`1. Hara T: [Increased iris pigmentation a(cid:813)er use of latanoprost in Japanese brown eyes]. Nippon Ganka
`Gakkai Zasshi. 2001 May;105(5):314-21. [PubMed:11406947]
`
`External Links
`
`Human Metabolome Database
`
`HMDB0014792
`
`KEGG Drug
`
`D00356
`
`PubChem Compound
`
`5311221
`
`PubChem Substance
`
`46506279
`
`ChemSpider
`
`4470740
`
`BindingDB
`
`50240648
`
`ChEBI
`
`6384
`
`h
`https://www.drugbank.ca/drugs/DB00654
`
`10/24
`
`Micro Labs Exhibit 1052-10
`
`
`
`6/1/2018
`ChEMBL
`
`CHEMBL1051
`
`Therapeutic Targets Database
`
`Latanoprost - DrugBank
`
`DAP001216
`
`PharmGKB
`
`PA164774763
`
`RxList
`
`RxList Drug Page
`
`Drugs.com
`
`Drugs.com Drug Page
`
`PDRhealth
`
`PDRhealth Drug Page
`
`Wikipedia
`
`Latanoprost
`
`ATC Codes
`
`S01EE01 — Latanoprost
`S01EE — Prostaglandin analogues
`S01E — ANTIGLAUCOMA PREPARATIONS AND MIOTICS
`S01 — OPHTHALMOLOGICALS
`S — SENSORY ORGANS
`
`AHFS Codes
`
`52:40.28 — Prostaglandin Analogs
`
`FDA label
`
`Download (502 KB)
`
`MSDS
`
`Download (21.1 KB)
`
`CLINICAL TRIALS
`
`Cli
`i
`l T i l
`https://www.drugbank.ca/drugs/DB00654
`
`11/24
`
`Micro Labs Exhibit 1052-11
`
`
`
`6/1/2018
`Clinical Trials
`
`Search
`
`Latanoprost - DrugBank
`
`PHASE ↑↓ STATUS ↑↓ PURPOSE ↑↓ CONDITIONS
`1
`Completed Not Available Glaucoma / Ocular Hypertension
`
`↑↓ COUNT ↑↓
`2
`
`1
`
`1
`
`1
`
`1
`
`1, 2
`
`1, 2
`
`1, 2
`
`2
`
`2
`
`Completed Treatment
`
`Glaucoma
`
`Completed Treatment
`
`Ocular Hypertension / Open-angle Glaucoma
`(OAG)
`
`Completed Treatment
`
`Open Angle Glaucoma -Ocular Hypertension
`
`Terminated Treatment
`
`Completed Treatment
`
`Glaucoma, Primary Open Angle (POAG) / Ocular
`Hypertension
`
`Glaucoma, Primary Open Angle (POAG) / Ocular
`Hypertension
`
`Completed Treatment
`
`Glaucoma / Ocular Hypertension
`
`Completed Treatment
`
`Ocular Hypertension / Open-angle Glaucoma
`(OAG)
`
`Active Not
`Recruiting
`
`Active Not
`Recruiting
`
`Treatment
`
`Childhood Glaucoma
`
`Treatment
`
`Menière's Disease
`
`1
`
`1
`
`1
`
`1
`
`1
`
`1
`
`1
`
`1
`
`1
`
`Showing 1 to 10 of 83 entries
`
`‹
`
`›
`
`PHARMACOECONOMICS
`
`Manufacturers
`
`Pharmacia and upjohn co
`
`Packagers
`
`Assia Chemical Industries Ltd.
`
`Cardinal Health
`
`Pfizer Inc.
`
`Pharmacia Inc.
`
`https://www.drugbank.ca/drugs/DB00654
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`12/24
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`Micro Labs Exhibit 1052-12
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`6/1/2018
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`Latanoprost - DrugBank
`
`Dosage forms
`
`Search
`
`FORM
`
`Solution
`
`Solution / drops
`
`Solution / drops
`
`Solution / drops
`
`Solution
`
`Solution
`
`↑↓
`
`↑↓ ROUTE
`Ophthalmic
`
`Ophthalmic
`
`Ophthalmic
`
`Ophthalmic
`
`Ophthalmic
`
`Ophthalmic
`
`↑↓ STRENGTH
`50 ug/mL
`
`50 ug/mL
`
`.05 mg/mL
`
`50 mcg
`
`Showing 1 to 6 of 6 entries
`
`‹
`
`›
`
`Prices
`
`Search
`
`UNIT DESCRIPTION
`
`Xalatan 0.005% Solution 2.5ml Bottle
`
`↑↓ COST
`93.59USD
`
`↑↓ UNIT
`bottle
`
`↑↓
`
`Xalatan 0.005% eye drops
`
`Xalatan 0.005 % Solution
`
`Showing 1 to 3 of 3 entries
`
`45.06USD
`
`12.18USD
`
`ml
`
`ml
`
`‹
`
`›
`
`DrugBank does not sell nor buy drugs. Pricing information is supplied for informational
`purposes only.
`
`Patents
`
`Search
`
`PATENT NUMBER ↑↓ PEDIATRIC EXTENSION ↑↓ APPROVED ↑↓ EXPIRES (ESTIMATED) ↑↓
`US5296504
`No
`1994-03-22
`2011-03-22
`
`↑↓
`
`https://www.drugbank.ca/drugs/DB00654
`
`13/24
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`Micro Labs Exhibit 1052-13
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`
`
`Latanoprost - DrugBank
`1992-09-06
`
`1997-07-29
`
`2009-09-06
`
`2014-07-29
`
`‹
`
`›
`
`VALUE
`
`8 mg/mL
`
`4.4
`
`SOURCE
`
`Not Available
`
`Not Available
`
`6/1/2018
`US6429226
`
`CA1339132
`
`No
`
`No
`
`Showing 1 to 3 of 3 entries
`
`PROPERTIES
`
`State
`
`Liquid
`
`Experimental Properties
`
`PROPERTY
`
`water solubility
`
`logP
`
`Predicted Properties
`
`Water Solubility
`
`0.0129 mg/mL
`
`ALOGPS
`
`logP
`
`4.16
`
`ALOGPS
`
`logP
`
`3.98
`
`ChemAxon
`
`logS
`
`-4.5
`
`ALOGPS
`
`pKa (Strongest Acidic)
`
`14 47
`https://www.drugbank.ca/drugs/DB00654
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`14/24
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`Micro Labs Exhibit 1052-14
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`6/1/2018
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`14.47
`
`Latanoprost - DrugBank
`
`ChemAxon
`
`pKa (Strongest Basic)
`
`-2.7
`
`ChemAxon
`
`Physiological Charge
`
`0 C
`
`hemAxon
`
`Hydrogen Acceptor Count
`
`4 C
`
`hemAxon
`
`Hydrogen Donor Count
`
`3 C
`
`hemAxon
`
`Polar Surface Area
`
`86.99 Å2
`
`ChemAxon
`
`Rotatable Bond Count
`
`14
`
`ChemAxon
`
`Refractivity
`
`3
`-1
`124.34 m ·mol
`
`ChemAxon
`
`Polarizability
`
`50.71 Å3
`
`ChemAxon
`
`Number of Rings
`
`2 C
`
`hemAxon
`
`Bioavailability
`
`1
`https://www.drugbank.ca/drugs/DB00654
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`15/24
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`Micro Labs Exhibit 1052-15
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`
`
`Latanoprost - DrugBank
`
`1 C
`
`hemAxon
`
`Rule of Five
`
`Yes
`
`ChemAxon
`
`Ghose Filter
`
`No
`
`ChemAxon
`
`Veber's Rule
`
`No
`
`ChemAxon
`
`MDDR-like Rule
`
`No
`
`ChemAxon
`
`6/1/2018
`
`Predicted ADMET features
`
`Human Intestinal Absorption
`
`+ B
`
`lood Brain Barrier
`
`+ C
`
`aco-2 permeable
`
`+ P
`
`-glycoprotein substrate
`
`Substrate
`
`P-glycoprotein inhibitor I
`
`Non-inhibitor
`
`P-glycoprotein inhibitor II
`
`Non-inhibitor
`
`Renal organic cation transporter
`
`Non-inhibitor
`
`CYP450 2C9 substrate
`https://www.drugbank.ca/drugs/DB00654
`
`16/24
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`Micro Labs Exhibit 1052-16
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`
`
`Latanoprost - DrugBank
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`6/1/2018
`
`CYP450 2C9 substrate
`
`Non-substrate
`
`CYP450 2D6 substrate
`
`Non-substrate
`
`CYP450 3A4 substrate
`
`Substrate
`
`CYP450 1A2 substrate
`
`Non-inhibitor
`
`CYP450 2C9 inhibitor
`
`Non-inhibitor
`
`CYP450 2D6 inhibitor
`
`Non-inhibitor
`
`CYP450 2C19 inhibitor
`
`Non-inhibitor
`
`CYP450 3A4 inhibitor
`
`Non-inhibitor
`
`CYP450 inhibitory promiscuity
`
`Low CYP Inhibitory Promiscuity
`
`Ames test
`
`Non AMES toxic
`
`Carcinogenicity
`
`Non-carcinogens
`
`Biodegradation
`
`Not ready biodegradable
`
`Rat acute toxicity
`
`4.3748 LD50, mol/kg
`
`hERG inhibition (predictor I)
`
`Weak inhibitor
`
`hERG inhibition (predictor II)
`
`Non-inhibitor
`
`https://www.drugbank.ca/drugs/DB00654
`
`17/24
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`Micro Labs Exhibit 1052-17
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`
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`6/1/2018
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`Latanoprost - DrugBank
`ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET
`properties. (23092397)
`
`SPECTRA
`
`Mass Spec (NIST)
`
`Not Available
`
`Spectra
`
`Predicted GC-MS Spectrum - GC-MS
`
`Predicted MS/MS Spectrum - 10V, Positive (Annotated)
`
`Predicted MS/MS Spectrum - 20V, Positive (Annotated)
`
`Predicted MS/MS Spectrum - 40V, Positive (Annotated)
`
`Predicted MS/MS Spectrum - 10V, Negative (Annotated)
`
`Predicted MS/MS Spectrum - 20V, Negative (Annotated)
`
`Predicted MS/MS Spectrum - 40V, Negative (Annotated)
`
`LC-MS/MS Spectrum - LC-ESI-qTof , Positive
`
`MS/MS Spectrum - , positive
`
`TAXONOMY
`
`Description
`
`This compound belongs to the class of organic compounds known as prostaglandins and
`related compounds. These are unsaturated carboxylic acids consisting of a 20 carbon skeleton
`that also contains a five member ring, and are based upon the fatty acid arachidonic acid.
`
`Kingdom
`
`Organic compounds
`
`Super Class
`
`Lipids and lipid-like molecules
`
`Class
`
`Fatty Acyls
`https://www.drugbank.ca/drugs/DB00654
`
`18/24
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`Micro Labs Exhibit 1052-18
`
`
`
`Latanoprost - DrugBank
`
`6/1/2018
`
`y
`
`y
`
`Sub Class
`
`Eicosanoids
`
`Direct Parent
`
`Prostaglandins and related compounds
`
`Alternative Parents
`
`Fatty acid esters / Cyclopentanols / Benzene and substituted derivatives / Cyclic alcohols and derivatives
`/ Carboxylic acid esters / Monocarboxylic acids and derivatives / Organic oxides /
`Hydrocarbon derivatives / Carbonyl compounds
`
`Substituents
`
`Prostaglandin skeleton / Fatty acid ester / Monocyclic benzene moiety / Cyclopentanol / Benzenoid /
`Cyclic alcohol / Carboxylic acid ester / Secondary alcohol / Carboxylic acid derivative /
`Monocarboxylic acid or derivatives
`
`Molecular Framework
`
`Aromatic homomonocyclic compounds
`
`External Descriptors
`
`carboxylic ester, prostaglandins Falpha, triol (CHEBI:6384)
`
`TARGETS
`
`1. Prostaglandin F2-alpha receptor
`
`Kind
`
`Protein
`
`Organism
`
`Human
`
`Pharmacological action
`
`Yes
`https://www.drugbank.ca/drugs/DB00654
`
`19/24
`
`Micro Labs Exhibit 1052-19
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`
`
`6/1/2018
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`Latanoprost - DrugBank
`
`Actions
`
`Agonist
`General Function
`
`Prostaglandin f receptor activity
`
`Specific Function
`
`Receptor for prostaglandin F2-alpha (PGF2-alpha). The activity of this receptor is
`mediated by G proteins which activate a phosphatidylinositol-calcium second
`messenger system. Initiates luteolysis...
`
`Gene Name
`
`PTGFR
`
`Uniprot ID
`
`P43088
`
`Uniprot Name
`
`Prostaglandin F2-alpha receptor
`
`Molecular Weight
`
`40054.1 Da
`
`References
`
`1. Ota T, Aihara M, Narumiya S, Araie M: The effects of prostaglandin analogues on IOP in
`prostanoid FP-receptor-deficient mice. Invest Ophthalmol Vis Sci. 2005 Nov;46(11):4159-63.
`[PubMed:16249494]
`2. Nakajima T, Matsugi T, Goto W, Kageyama M, Mori N, Matsumura Y, Hara H: New
`fluoroprostaglandin F(2alpha) derivatives with prostanoid FP-receptor agonistic activity as
`potent ocular-hypotensive agents. Biol Pharm Bull. 2003 Dec;26(12):1691-5.
`[PubMed:14646172]
`3. Takagi Y, Nakajima T, Shimazaki A, Kageyama M, Matsugi T, Matsumura Y, Gabelt BT, Kaufman
`PL, Hara H: Pharmacological characteristics of AFP-168 (tafluprost), a new prostanoid FP
`receptor agonist, as an ocular hypotensive drug. Exp Eye Res. 2004 Apr;78(4):767-76.
`[PubMed:15037111]
`4. Ocklind A: Effect of latanoprost on the extracellular matrix of the ciliary muscle. A study on
`cultured cells and tissue sections. Exp Eye Res. 1998 Aug;67(2):179-91. [PubMed:9733584]
`5. Maxey KM, Johnson JL, LaBrecque J: The hydrolysis of bimatoprost in corneal tissue
`generates a potent prostanoid FP receptor agonist. Surv Ophthalmol. 2002 Aug;47 Suppl
`1:S34-40. [PubMed:12204699]
`
`6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan
`1;30(1):412-5. [PubMed:11752352]
`
`https://www.drugbank.ca/drugs/DB00654
`
`20/24
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`Micro Labs Exhibit 1052-20
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`
`
`6/1/2018
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`Latanoprost - DrugBank
`
`TRANSPORTERS
`
`1. Solute carrier organic anion transporter family member 2B1
`
`Kind
`
`Protein
`
`Organism
`
`Human
`
`Pharmacological action
`
`Unknown
`
`Actions
`
`Substrate
`General Function
`
`Sodium-independent organic anion transmembrane transporter activity
`
`Specific Function
`
`Mediates the Na(+)-independent transport of organic anions such as taurocholate, the
`prostaglandins PGD2, PGE1, PGE2, leukotriene C4, thromboxane B2 and iloprost.
`
`Gene Name
`
`SLCO2B1
`
`Uniprot ID
`
`O94956
`
`Uniprot Name
`
`Solute carrier organic anion transporter family member 2B1
`
`Molecular Weight
`
`76709.98 Da
`
`References
`
`1. Kra(cid:813) ME, Glaeser H, Mandery K, Konig J, Auge D, Fromm MF, Schlotzer-Schrehardt U, Welge-
`Lussen U, Kruse FE, Zolk O: The prostaglandin transporter OATP2A1 is expressed in human
`l
`ti
`d t
`t th
`ti
`l
`t
`id l t
`t I
`t O hth l
`https://www.drugbank.ca/drugs/DB00654
`
`l
`
`21/24
`
`Micro Labs Exhibit 1052-21
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`
`
`6/1/2018
`
`Latanoprost - DrugBank
`ocular tissues and transports the antiglaucoma prostanoid latanoprost. Invest Ophthalmol
`Vis Sci. 2010 May;51(5):2504-11. doi: 10.1167/iovs.09-4290. Epub 2009 Dec 17.
`[PubMed:20019365]
`
`2. Solute carrier family 22 member 1
`
`Kind
`
`Protein
`
`Organism
`
`Human
`
`Pharmacological action
`
`Unknown
`General Function
`
`Secondary active organic cation transmembrane transporter activity
`
`Specific Function
`
`Translocates a broad array of organic cations with various structures and molecular
`weights including the model compounds 1-methyl-4-phenylpyridinium (MPP),
`tetraethylammonium (TEA), N-1-methylnico...
`
`Gene Name
`
`SLC22A1
`
`Uniprot ID
`
`O15245
`
`Uniprot Name
`
`Solute carrier family 22 member 1
`
`Molecular Weight
`
`61153.345 Da
`
`References
`
`1. Kimura H, Takeda M, Narikawa S, Enomoto A, Ichida K, Endou H: Human organic anion
`transporters and human organic cation transporters mediate renal transport of
`l di
`h
`l
`h
`( )
`[ b
`d
`]
`https://www.drugbank.ca/drugs/DB00654
`
`22/24
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`Micro Labs Exhibit 1052-22
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`
`
`6/1/2018
`
`Latanoprost - DrugBank
`prostaglandins. J Pharmacol Exp Ther. 2002 Apr;301(1):293-8. [PubMed:11907186]
`
`Drug created on June 13, 2005 07:24 / Updated on May 31, 2018 10:03
`
`About
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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 funding from the federal government. Maintenance,
`support, and commercial licensing is provided by OMx Personal Health Analytics, Inc. Designed by Educe
`Design & Innovation Inc.
`
`https://www.drugbank.ca/drugs/DB00654
`
`23/24
`
`Micro Labs Exhibit 1052-23
`
`
`
`6/1/2018
`
`Latanoprost - DrugBank
`
`https://www.drugbank.ca/drugs/DB00654
`
`24/24
`
`Micro Labs Exhibit 1052-24
`
`
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