PRADIGASTAT

Details

Stereochemistry	ACHIRAL
Molecular Formula	C25H24F3N3O2
Molecular Weight	455.4722
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC(=O)C[C@H]1CC[C@@H](CC1)C2=CC=C(C=C2)C3=CC=C(NC4=CC=C(N=C4)C(F)(F)F)C=N3

InChI

InChIKey=GXALXAKNHIROPE-QAQDUYKDSA-N

InChI=1S/C25H24F3N3O2/c26-25(27,28)23-12-10-21(15-30-23)31-20-9-11-22(29-14-20)19-7-5-18(6-8-19)17-3-1-16(2-4-17)13-24(32)33/h5-12,14-17,31H,1-4,13H2,(H,32,33)/t16-,17-

HIDE SMILES / InChI

Molecular Formula	C25H24F3N3O2
Molecular Weight	455.4722
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.rareconnect.org/uploads/documents/lcq908-pradigastat-for-familial-chylomicronaemia-syndrome-first-line.pdf
Curator's Comment: Description was created based on several sources, including http://adisinsight.springer.com/drugs/800030516

LCQ908 (Pradigastat) is a diacylglycerol acyltransferase-1 (DGAT-1) inhibitor. DGAT-1 is one of the two DGAT enzymes that catalyse the formation of triglycerides from diacylglycerol and acyl- coenzyme A. DGAT-1 catalyses the final committed step in processing dietary fatty acids into triglycerides carried on chylomicrons for transport around the body. Pradigastat may decrease the level of triglycerides in the blood and is intended for the first line treatment of FCS. It is administered orally at 10-40mg daily in addition to a low fat diet. Pradigastat is also in phase II clinical trials for type 2 diabetes and severe hypertriglyceridaemia (familial hyperchylomicronaemia phenotypes I and V). Pradigastat is a designated orphan drug in the EU. In a phase III clinical trial.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Diacylglycerol O-acyltransferase 1 7 Target ID: CHEMBL6009 Sources: https://www.rareconnect.org/uploads/documents/lcq908-pradigastat-for-familial-chylomicronaemia-syndrome-first-line.pdf	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Familial chylomicronemia syndrome 2 Sources: https://clinicaltrials.gov/ct2/show/NCT01514461	Primary		Phase III 656	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
1065 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25854859	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	PRADIGASTAT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FASTED
184 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25627776	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:	PRADIGASTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
10500 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27274009	115 mg single, intravenous dose: 115 mg route of administration: Intravenous experiment type: SINGLE co-administered:	PRADIGASTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
18561 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25854859	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	PRADIGASTAT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FASTED
37200 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25627776	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:	PRADIGASTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
428000 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27274009	115 mg single, intravenous dose: 115 mg route of administration: Intravenous experiment type: SINGLE co-administered:	PRADIGASTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
80.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25854859	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	PRADIGASTAT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FASTED
145 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25627776	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:	PRADIGASTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
109 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27274009	115 mg single, intravenous dose: 115 mg route of administration: Intravenous experiment type: SINGLE co-administered:	PRADIGASTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
0.6% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25627776	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:		PRADIGASTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

Doses

Dose	Population	Adverse events
300 mg single, oral Highest studied dose Dose: 300 mg Route: oral Route: single Dose: 300 mg Sources: https://pubmed.ncbi.nlm.nih.gov/25854859 Page: p.1037	unhealthy, ADULT n = 8 Health Status: unhealthy Condition: obesity Age Group: ADULT Sex: M Food Status: FASTED Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/25854859 Page: p.1037	Sources: https://pubmed.ncbi.nlm.nih.gov/25854859 Page: p.1037
115 mg single, intravenous Studied dose Dose: 115 mg Route: intravenous Route: single Dose: 115 mg Sources: https://pubmed.ncbi.nlm.nih.gov/27274009 Page: p.9	healthy, ADULT n = 9 Health Status: healthy Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 9 Sources: https://pubmed.ncbi.nlm.nih.gov/27274009 Page: p.9	Sources: https://pubmed.ncbi.nlm.nih.gov/27274009 Page: p.9

Sourcing

Vendor/Aggregator	ID	URL
Compound Cloud	53387034
Compound Cloud	53387035
Hairui	PRSA022	http://www.hairuichem.com/en/product/search.do?q=PRSA022
Synovel	SN-0620	http://www.synovellab.com/?s=SN-0620&submit=Search
eMolecules	275134991	https://orderbb.emolecules.com/search/#?query=275134991
eMolecules	300766254	https://orderbb.emolecules.com/search/#?query=300766254

PubMed

Title	Date	PubMed

Patents

Sample Use Guides

In Vivo Use Guide

Experimental: LCQ908 (Pradigastat) 20 mg In period II (0-12 weeks) double-blind treatment: one LCQ908 (Pradigastat) 20 mg active tablet, once daily In period III (12-52 weeks) double blind treatment: Without down titration, the period II dosing regimen will follow. Following decision to down titrate: one LCQ908 (Pradigastat) 10 mg active tablet, once daily.

Route of Administration: Oral

In Vitro Use Guide

Unknown

Substance Class	Chemical Created by `admin` on `Sat Dec 16 00:14:08 GMT 2023` Edited by `admin` on `Sat Dec 16 00:14:08 GMT 2023`
Record UNII	2U23G6VNUZ
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

PRADIGASTAT

Official Name

English

LCQ-908-NXA

Code

English

LCQ-908NXA

Code

English

LCQ-908

Common Name

English

LCQ908-NXA

Code

English

LCQ908 - DGAT-1-INHIBITOR

Common Name

English

pradigastat [INN]

Common Name

English

PRADIGASTAT [USAN]

Common Name

English

CYCLOHEXANEACETIC ACID, 4-(4-(5-((6-(TRIFLUOROMETHYL)-3-PYRIDINYL)AMINO)-2-PYRIDINYL)PHENYL)-, TRANS-

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

335711