 Home > Encyclopedia > lifitegrast

lifitegrast

lifitegrast structure

CAS No:
1025967-78-5
Formula:
C29H24Cl2N2O7S
Chemical Name:
lifitegrast
Synonyms:
CS-2633;Lifitegrast（API）;SAR-1118;SAR1118;Lifitegrast-d4;Lifitegrast Impurity;lifitegrast;Lifitegrast, SAR 1118;L-Phenylalanine,N-[[2-(6-benzofuranylcarbonyl)-5,7-dichloro-1,2,3,4-tetrahydro-6-isoquinolinyl]carbonyl]-3-(methylsulfonyl)-
Categories:
Pharmaceutical Intermediates > Bulk Drug Intermediates

Description

Lifitegrast is an N-acyl-L-alpha-amino acid obtained by formal condensation of the carboxy group of N-[2-(1-benzofuran-6-carbonyl)]-5,7-dichloro-1,2,3,4-tetrahydroisoquinoline-6-carboxylic acid with the amino group of 3-(methanesulfonyl)-L-phenylalanine. Used for treatment of keratoconjunctivitis sicca (dry eye syndrome). It has a role as an anti-inflammatory drug and a lymphocyte function-associated antigen-1 antagonist. It is a L-phenylalanine derivative, a sulfone, a N-acyl-L-alpha-amino acid, a member of isoquinolines and a member of 1-benzofurans.|Lifitegrast is a FDA approved drug for the treatment of keratoconjunctivitis sicca (dry eye syndrome). It is a tetrahydroisoquinoline derivative and lymphocyte function-associated antigen-1 ( LFA-1) antagonist that was discovered through the rational design process. The ophthalmic solution was approved in July, 2016 under the trade name Xiidra. It has shown to protect the corneal surface and alleviate the symptoms of dry eye syndrome with fast onset of action and well tolerated profile in both local and systemic setting.|Lifitegrast is a Lymphocyte Function-Associated Antigen-1 Antagonist. The mechanism of action of lifitegrast is as a Lymphocyte Function-Associated Antigen-1 Antagonist.

Lifitegrast (Xiidra; lifitegrast sodium; SAR1118; SHP606; SPD606) is a lymphocyte functionassociated antigen-1 (LFA-1) antagonist. It inhibits T-cell inflammation by blocking the binding of two key surface proteins (LFA-1 and ICAM-1) that mediate the chronic inflammatory cascade associated with dry eye disease. In a phase III clinical trial, lifitegrast 5% ophthalmic solution (50 mg/mL) is administered as a single 0.2mL eye drop twice a day into each eye for an 84 day treatment period.Lifitegrast does not currently have Marketing Authorisation in the EU for any indication. Lifitegrast is licensed for use in the USA for treatment of the signs and symptoms of dry eye disease. The most common adverse reactions (incidence 5-25%) reported following the use of lifitegrast are instillation site irritation, dysgeusia, and decreased visual acuity.

Lifitegrast is a white to off-white powder which is soluble in water.

lifitegrast Basic Attributes

Molecular Weight：

615.48

Exact Mass：

615.48

EC Number：

813-044-8

UNII：

038E5L962W

DSSTox ID：

DTXSID60145345

Color/Form：

White to Off-White

ATC Code：

S - Sensory organs

Characteristics

Density：

1.479±0.06 g/cm3(Predicted)

Melting Point：

>163°C (dec.)

Boiling Point：

811.9±65.0 °C(Predicted)

Water Solubility：

Soluble

PKA：

3.14±0.10(Predicted)

Critical Temperature & Pressure：

Hygroscopic, -20°C Freezer, Under inert atmosphere

Safety Information

GHS Classification：

|Warning|H361 (100%): Suspected of damaging fertility or the unborn child [Warning Reproductive toxicity]|P201, P202, P281, P308+P313, P405, and P501|Aggregated GHS information provided by 3 companies from 1 notifications to the ECHA C&L Inventory.

Toxicity

Toxicity Summary：

Some adverse effects in 5-25% of the patients include instillation site irritation, dysgeusia and reduced visual acuity. There is no evidence or reports of potential carcinogenic, mutagenic or fertility-altering effects of this drug.

Protein Binding：

Human plasma protein binding of lifitegrast was approximately 99%, independent of concentration (50 to 1000ng/mL). Binding to isolated human serum albumin was 95% to 98%, and 31.6% to 51.1% to human α1-acid glycoprotein.

Drug Information

Drug Indication：

For the treatment of signs and symptoms of keratoconjunctivitis sicca (dry eye syndrome).|FDA Label|Treatment of dry eye disease

Pharmacology：

Lifitegrast addresses both the symptoms and the resulting ocular surface damage by interfering with ocular inflammatory cycle. Lifitegrast is a lymphocyte function–associated antigen-1 antagonist through direct competitive antagonism and sequentially inhibits the T-cell recruitment, activation, and proinflammatory cytokine release associated with dry eye syndrome.

MeSH：

Sterile solutions that are intended for instillation into the eye. It does not include solutions for cleaning eyeglasses or CONTACT LENS SOLUTIONS. (See all compounds classified as Ophthalmic Solutions.)

Absorption：

The mean peak plasma concentration (Cmax) of 1.70ng/mL was reached within 15 minutes of application. Quantifiable trough plasma concentrations ranged from 0.55 ng/mL to 3.74 ng/mL. Observations show limited systemic exposure that produces significant clinical outcomes.|Not possible to perform mass balance study to determine the main route of elimination.|Not possible to calculate clearance rate based on plasma concentrations of lifitegrast, but reported to be relatively fast in rat I.V. pharmacokinetics study. It is predicted that lifitegrast is cleared via nasal and subsequently gastrointestinal tract.

Metabolism/Metabolites：

Based on the findings of an in vitro metabolism study using fresh human hepatocytes, lifitegrast does not appear to undergo significant metabolism.

Biological Half-Life：

Not possible to calculate plasma elimination half-life based on plasma concentrations of lifitegrast, but reported to be relatively short in rat I.V. pharmacokinetics study.

Mechanism of Action：

Lifitegrast binds to the integrin lymphocyte function-associated antigen-1 (LFA-1), a cell surface protein found on leukocytes and blocks the interaction of LFA-1 with its cognate ligand intercellular adhesion molecule-1 (ICAM-1). ICAM-1 may be overexpressed in corneal and conjunctival tissues in dry eye disease. LFA-1/ICAM-1 interaction can contribute to the formation of an immunological synapse resulting in T-cell proliferation/activation and migration to target tissues. In vitro studies demonstrated that lifitegrast may inhibit T-cell adhesion to ICAM-1 in a human T-cell line and may inhibit secretion of inflammatory cytokines, inflammatory mediators, chemokines, TNF-α, and IL-1 in human peripheral blood mononuclear cells.

MeSH Entry Terms：

(2S)-2-(((2-(benzofuran-6-ylcarbonyl)-5,7-dichloro-1,2,3,4-tetrahydroisoquinolin-6- yl)carbonyl)amino)-3-(3-(methylsulfonyl)phenyl)propanoic acid

lifitegrast Use and Manufacturing

Uses

Lifitegrast is used for the treatment of signs and symptons of dry eye diseases. It also Inhibites corneal inflammation that is capable of causing pains, blurred vision and ocular discomfort in sufferer.

Use Classification：

Human Drugs -> EU pediatric investigation plans|Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients

Recommended Suppliers of lifitegrast

Hangzhou KieRay Chem Co.,LTD Contact Supplier

CN
5 YRS

Business licensed Certified factory

Manufactory Supplier of fine chemicals,pharmaceutical materials

lifitegrast

CAS No.: 1025967-78-5

Grade: industrial Grade

Content: 98%

Inquiry
Hangzhou Royalchem Co.,LTD Contact Supplier

CN
1 YR

Business licensed

Trader Supplier of Pharmaceutical intermediates

Lifitegrast RC00105

CAS No.: 1025967-78-5

Grade: Pharmaceutical Grade

Content: 95.0%

Inquiry
ROYAL PHARM Contact Supplier

CN
4 YRS

Business licensed

Trader Supplier of additives,pharmaceutical chemicals,organic intermediate,chemical intermediates,Pharmaceutical Intermediates,catalyst,API

Lifitegrast CAS No.1025967-78-5

CAS No.: 1025967-78-5

Grade: Pharmaceutical grade

Content: 99%

Inquiry
Shandong Airuike Chemical Co., Ltd. Contact Supplier

CN
3 YRS

Business licensed

Trader Supplier of api,Intermediates,Organic Chemistry,Inorganic Chemistry,Daily Chemicals,Cosmetic Raw Materals,CATALYST AND AUXILIARY,FLAVORS AND FRAGRANCES,Chemical Pesticides,ADDITIVE

cas1025967-78-5 Lifitegrast

CAS No.: 1025967-78-5

Grade: Pharmaceutical Grade

Content: 99%

Inquiry
Alicorn Pharmaceutical Contact Supplier

CN
4 YRS

Business licensed Certified factory

Manufactory Supplier of Betahistine Mesylate,Azilsartan Medoxomil Potassium,Pimavanserin Tartrate,Iguratimod

Lifitegrast api

CAS No.: 1025967-78-5

Grade: Pharmaceutical Grade

Content: 99%

Inquiry