FILGOTINIB HYDROCHLORIDE

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C21H23N5O3S.ClH.3H2O
Molecular Weight	516.011
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

O.O.O.Cl.O=C(NC1=NN2C(C=CC=C2C3=CC=C(CN4CCS(=O)(=O)CC4)C=C3)=N1)C5CC5

InChI

InChIKey=VLVWKOPMGYYNKV-UHFFFAOYSA-N

InChI=1S/C21H23N5O3S.ClH.3H2O/c27-20(17-8-9-17)23-21-22-19-3-1-2-18(26(19)24-21)16-6-4-15(5-7-16)14-25-10-12-30(28,29)13-11-25;;;;/h1-7,17H,8-14H2,(H,23,24,27);1H;3*1H2

HIDE SMILES / InChI

Description

Filgotinib (GLPG0634) is a highly selective JAK1 inhibitor. GLPG0634 is a promising drug candidate for the future treatment of autoimmune and inflammatory disorders. It is in phase III clinical trials (initiated mid-2016) for the treatment of rheumatoid arthritis, Crohn's disease and ulcerative colitis. Most common adverse events observed were infections, gastrointestinal disorders and nervous system disorders.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Tyrosine-protein kinase JAK1	Inhibitor	10.0 nM [IC50]
Tyrosine-protein kinase JAK2	Inhibitor	28.0 nM [IC50]
Tyrosine-protein kinase JAK3	Inhibitor	810.0 nM [IC50]
Tyrosine-protein kinase TYK2	Inhibitor	116.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Crohn's disease	Primary	Phase III	Unknown
Ulcerative colitis	Primary	Phase III	Unknown
Rheumatoid arthritis	Primary	Phase III	Unknown

C_max

Value	Dose	Analyte	Population
2580 ng/mL	450 mg 1 times / day multiple, oral	FILGOTINIB plasma	Homo sapiens
1160 ng/mL	200 mg single, oral	FILGOTINIB plasma	Homo sapiens
4.42 μg/mL	450 mg 1 times / day multiple, oral	FILGOTINIB plasma	Homo sapiens
565 ng/mL	100 mg single, oral	FILGOTINIB plasma	Homo sapiens
556 ng/mL	100 mg 2 times / day steady-state, oral	FILGOTINIB plasma	Homo sapiens

AUC

Value	Dose	Analyte	Population
10200 ng × h/mL	450 mg 1 times / day multiple, oral	FILGOTINIB plasma	Homo sapiens
4844 ng × h/mL	200 mg single, oral	FILGOTINIB plasma	Homo sapiens
16.3 μg × h/mL	450 mg 1 times / day multiple, oral	FILGOTINIB plasma	Homo sapiens
1743 ng × h/mL	100 mg single, oral	FILGOTINIB plasma	Homo sapiens
2380 ng × h/mL	100 mg 2 times / day steady-state, oral	FILGOTINIB plasma	Homo sapiens

T_1/2

Value	Dose	Analyte	Population
7.09 h	450 mg 1 times / day multiple, oral	FILGOTINIB plasma	Homo sapiens
5.68 h	200 mg single, oral	FILGOTINIB plasma	Homo sapiens
4.91 h	100 mg single, oral	FILGOTINIB plasma	Homo sapiens
5.87 h	100 mg 2 times / day steady-state, oral	FILGOTINIB plasma	Homo sapiens

F_unbound

Value	Dose	Co-administered	Analyte	Population
42.5%			FILGOTINIB plasma	Homo sapiens

Doses

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Dose	Population	Adverse events
450 mg 1 times / day multiple, oral Highest studied dose	healthy, ADULT	Disc. AE: Skin rash...

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AEs

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AE	Significance	Dose	Population
Skin rash	grade 1, 2.1% Disc. AE	450 mg 1 times / day multiple, oral Highest studied dose	healthy, ADULT

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Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inducer	inhibitor	inhibitor	inhibitor

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2A6 UGT1A1 UGT1A4 UGT1A6 CYP1A2 CYP2B6 CYP2E1 UGT1A9 CYP3A4/5 CYP2C8 CYP2C19 UGT2B7 P-gp OCT2 OCT1 OAT3 OAT1 OATP1B3 OCT3 BSEP OATP1B1 BCRP MATE1 OAT2 MATE2-K	CES1b CES1c CES2 P-gp BCRP OATP1B1 OATP1B3	CYP1A2 CYP2B6

Drug as perpetrator

Show entries

Target	Modality	Activity	Metabolite
OATP1B1	inhibitor	no [IC50 110 uM]
OCT1	inhibitor	no [IC50 140 uM]	GS-829845
OCT1	inhibitor	no [IC50 151.6 uM]
OATP1B3	inhibitor	no [IC50 158 uM]	GS-829845
OATP1B3	inhibitor	no [IC50 168 uM]

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Drug as victim

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Target	Modality	Activity
CES2	substrate	major
CES1b	substrate	minor
CES1c	substrate	minor
BCRP	substrate	no
OATP1B1	substrate	no

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Tox targets

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Target	Modality	Activity	Metabolite	Clinical evidence
hERG	inhibitor

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PubMed

Title	Date	PubMed
No data available in table

Patents

Sample Use Guides

In Vivo Use Guide

Daily dose range up to 200 mg

Route of Administration: Oral

In Vitro Use Guide

Filgotinib inhibited IL-2– and IL-4–induced JAK1/JAK3/γc signaling and IFN-αB2–induced JAK1/TYK2 type II receptor signaling most potently. IC50 values ranged from 150 to 760 nM.

Show entries

Name

Type

Language

FILGOTINIB HYDROCHLORIDE

Official Name

English

FILGOTINIB HYDROCHLORIDE [USAN]

Common Name

English

G146034_101

Code

English

GLPG-0634

Code

English

G-146034_101

Code

English

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Code System

Code

Type

Description

EVMPD

SUB197230

PRIMARY

FDA UNII

2CQ8Y0B8XQ

PRIMARY

ChEMBL

CHEMBL3301607

PRIMARY

CAS

1540859-07-1

PRIMARY

NCI_THESAURUS

C166565

PRIMARY

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ACTIVE MOIETY


					3XVL385Q0M

FILGOTINIB

SUBSTANCE RECORD


					2CQ8Y0B8XQ

FILGOTINIB HYDROCHLORIDE

SMILES

InChI

Originator

Approval Year

Targets

Conditions

Cmax

AUC

T1/2

Funbound

Doses

AEs

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

Tox targets

PubMed

Patents

Sample Use Guides

C_max

T_1/2

F_unbound

Drug as perpetrator