LATANOPROST

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C26H40O5
Molecular Weight	432.5928
Optical Activity	UNSPECIFIED
Defined Stereocenters	5 / 5
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

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)CCC2=CC=CC=C2

InChI

InChIKey=GGXICVAJURFBLW-CEYXHVGTSA-N

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

HIDE SMILES / InChI

Molecular Formula	C26H40O5
Molecular Weight	432.5928
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	5 / 5
E/Z Centers	1
Optical Activity	UNSPECIFIED

Description

Latanoprost (free acid) is a metabolite of latanoprost which has been approved for use as an ocular hypotensive drug. Latanoprost is an isopropyl ester prodrug which is converted to the Latanoprost-acid by endogenous esterase enzymes. The free acid is pharmacologically active and is 200 times more potent than latanoprost as an agonist of the human recombinant Prostaglandin F receptor. However, the free Latanoprost-acid is more irritating and less effective than Latanoprost when applied directly to the eyes of human glaucoma patients.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Prostaglandin F2-alpha receptor 12	Agonist 2,752	3.6 nM [EC50]
Prostanoid FP receptor 21	Agonist 2,752
Prostanoid FP receptor 21	Agonist 2,752

Conditions

Condition	Modality	Highest Phase	Product
Open-angle glaucoma 53	Primary	Approved 8,583	VYZULTA
Ocular hypertension 52	Primary	Approved 8,583	VYZULTA
Open-angle glaucoma 53	Primary	Approved 8,583	VYZULTA
Ocular hypertension 52	Primary	Approved 8,583	VYZULTA
Open-angle glaucoma 53	Palliative	Approved 8,583	XALATAN
Ocular hypertension 52	Primary	Approved 8,583	XALATAN

C_max

Value	Dose	Co-administered	Analyte	Population
56.95 pg/mL	2 drop 1 times / day multiple, ocular		LATANOPROST ACID plasma	Homo sapiens
42.3 pg/mL	2 drop 1 times / day multiple, ocular		LATANOPROST ACID plasma	Homo sapiens
53 pg/mL	1.5 μg single, ocular		LATANOPROST ACID plasma	Homo sapiens
0.0636 ng × eq/mL	2.3 μg single, ocular		LATANOPROST plasma	Homo sapiens
12.43 ng × eq/mL	216.1 μg single, intravenous		LATANOPROST plasma	Homo sapiens
0.053 ng × eq/mL	2.3 μg single, ocular		LATANOPROST ACID plasma	Homo sapiens
11.6 ng × eq/mL	216.1 μg single, intravenous		LATANOPROST ACID plasma	Homo sapiens
30.4 ng/mL	1.5 μg single, ocular	TIMOLOL MALEATE	LATANOPROST ACID aqueous humor	Homo sapiens
19.77 pg/mL	2 drop 1 times / day multiple, ocular		LATANOPROST ACID plasma	Homo sapiens
18.47 pg/mL	2 drop 1 times / day multiple, ocular		LATANOPROST ACID plasma	Homo sapiens

AUC

Value	Dose	Co-administered	Analyte	Population
7.15 ng × h/mL	3 μg/kg bw single, intravenous		LATANOPROST ACID plasma	Homo sapiens
34 pg × h/mL	1.5 μg single, ocular		LATANOPROST ACID plasma	Homo sapiens
0.165 ng × eq × h/mL	2.3 μg single, ocular		LATANOPROST plasma	Homo sapiens
20.2 ng × eq × h/mL	216.1 μg single, intravenous		LATANOPROST plasma	Homo sapiens
0.0337 ng × eq × h/mL	2.3 μg single, ocular		LATANOPROST ACID plasma	Homo sapiens
7.15 ng × eq × h/mL	216.1 μg single, intravenous		LATANOPROST ACID plasma	Homo sapiens
206 ng × h/mL	1.5 μg single, ocular	TIMOLOL MALEATE	LATANOPROST ACID aqueous humor	Homo sapiens
6.15 pg × h/mL	2 drop 1 times / day multiple, ocular		LATANOPROST ACID plasma	Homo sapiens
4.97 pg × h/mL	2 drop 1 times / day multiple, ocular		LATANOPROST ACID plasma	Homo sapiens

T_1/2

Value	Dose	Co-administered	Analyte	Population
16.6 min	3 μg/kg bw single, intravenous		LATANOPROST ACID plasma	Homo sapiens
17 min	1.5 μg single, ocular		LATANOPROST ACID plasma	Homo sapiens
1.842 h	2.3 μg single, ocular		LATANOPROST plasma	Homo sapiens
1.471 h	216.1 μg single, intravenous		LATANOPROST plasma	Homo sapiens
17 min	2.3 μg single, ocular		LATANOPROST ACID plasma	Homo sapiens
16.6 min	216.1 μg single, intravenous		LATANOPROST ACID plasma	Homo sapiens
2.3 h	1.5 μg single, ocular	TIMOLOL MALEATE	LATANOPROST ACID aqueous humor	Homo sapiens
0.3 h	2 drop 1 times / day multiple, ocular		LATANOPROST ACID plasma	Homo sapiens
0.2 h	2 drop 1 times / day multiple, ocular		LATANOPROST ACID plasma	Homo sapiens

F_unbound

Value	Dose	Co-administered	Analyte	Population
47%			LATANOPROST plasma	Homo sapiens

Doses

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Dose	Population	Adverse events
10 ug 1 times / day multiple, topical Highest studied dose	healthy, ADULT	Other AEs: Ocular discomfort, Hyperemia...
10 ug single, topical Highest studied dose	healthy, ADULT	Other AEs: Hyperemia...
0.005 % 1 times / day multiple, topical Recommended	unhealthy, ADULT	Disc. AE: Eye irritation, Asthenopia...
0.005 % 1 times / day multiple, topical Recommended	unhealthy, ADULT	Disc. AE: Cystoid macular edema, Iritis...
0.005 % 1 times / day multiple, topical Recommended	unhealthy, ADULT	Disc. AE: Conjuncitivitis, Ocular hyperemia...

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AEs

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AE	Significance	Dose	Population
Hyperemia	50%	10 ug 1 times / day multiple, topical Highest studied dose	healthy, ADULT
Ocular discomfort	grade 1, 50%	10 ug 1 times / day multiple, topical Highest studied dose	healthy, ADULT
Hyperemia	grade 2	10 ug single, topical Highest studied dose	healthy, ADULT
Asthenopia	Disc. AE	0.005 % 1 times / day multiple, topical Recommended	unhealthy, ADULT
Eye irritation	Disc. AE	0.005 % 1 times / day multiple, topical Recommended	unhealthy, ADULT

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Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYPs 29 CYP450 25	CYP 303 OATP2B1 122 MRP1 113 MRP2 252 MRP5 41 P-gp 2,052 BCRP 697	CYPs 17 CYP450 32

Drug as perpetrator

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Target	Modality	Activity
CYPs 35	inhibitor 4,027	no
CYP450 41	inducer 1,966	unlikely
CYP450 41	inhibitor 4,027	unlikely
CYPs 35	inducer 1,966	unlikely

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Drug as victim

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Target	Modality	Activity
CYP 303	substrate 4,014	no
P-gp 2,052	substrate 4,014	no
BCRP 697	substrate 4,014	unlikely
OATP2B1 122	substrate 4,014	weak
MRP1 113	substrate 4,014	yes

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Sourcing

Sourcing

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Vendor/Aggregator	ID	URL
AA Blocks	AA00BXFY	https://www.aablocks.com/goods/Goods/detail?id=AA00BXFY
Aaron Chemicals	AR00BY7Q	http://www.aaronchem.com/41639-83-2
Achemtek	0104-022891	http://www.achemtek.com/41639-83-2
AK Scientific, Inc. (AKSCI)	Z6154	http://www.aksci.com/item_detail.php?cat=Z6154
Alfa Chemistry	AP41639832-A	https://reagents.alfa-chemistry.com/product/latanoprost-related-compound-e-cas-41639-83-2-11264.html

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PubMed

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Title	Date	PubMed
The utilization of recombinant prostanoid receptors to determine the affinities and selectivities of prostaglandins and related analogs.	2000 Jan 17	10634944
Efficacy and safety of latanoprost versus pilocarpine/timolol maleate fixed combination in patients with primary open-angle glaucoma or ocular hypertension.	2008 Dec	18721251
A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development.	2013 Nov	23956101
Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis.	2015 May 18	25811541

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Patents

Sample Use Guides

In Vivo Use Guide

One drop in the affected eye(s) once daily in the evening.

Route of Administration: Other

In Vitro Use Guide

Latanoprost above concentrations of 3.125 mg/l can induce dose- and time-dependent morphological abnormality, growth retardation, viability decline, and plasma membrane permeability elevation of human corneal stromal (HCS) cells. Moreover, latanoprost can arrest the cell cycle of these cells at S phase and induce PS externalization, DNA fragmentation, and apoptotic body formation of the cells. Furthermore, latanoprost can induce activation of caspase-3, -8 and -9; disruption of MTP; downregulation of anti-apoptotic Bcl-2; upregulation of pro-apoptotic Bax; and cytoplasmic cytochrome c release