FILGOTINIB MALEATE

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C21H23N5O3S.C4H4O4
Molecular Weight	541.576
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

SMILES

OC(=O)\C=C/C(O)=O.O=C(NC1=NN2C(C=CC=C2C3=CC=C(CN4CCS(=O)(=O)CC4)C=C3)=N1)C5CC5

InChI

InChIKey=BFENHEAPFWQJFL-BTJKTKAUSA-N

InChI=1S/C21H23N5O3S.C4H4O4/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;5-3(6)1-2-4(7)8/h1-7,17H,8-14H2,(H,23,24,27);1-2H,(H,5,6)(H,7,8)/b;2-1-

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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 38	Inhibitor 8,297	10.0 nM [IC50]
Tyrosine-protein kinase JAK2 55	Inhibitor 8,297	28.0 nM [IC50]
Tyrosine-protein kinase JAK3 27	Inhibitor 8,297	810.0 nM [IC50]
Tyrosine-protein kinase TYK2 16	Inhibitor 8,297	116.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Crohn's disease 42	Primary	Phase III 656	Unknown
Ulcerative colitis 123	Primary	Phase III 656	Unknown
Rheumatoid arthritis 316	Primary	Phase III 656	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 781	inhibitor 1,767	inhibitor 1,852	inhibitor 1,612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2A6 707 UGT1A1 204 UGT1A4 77 UGT1A6 108 CYP1A2 1,524 CYP2B6 810 CYP2E1 882 UGT1A9 116 CYP3A4/5 278 CYP2C8 911 CYP2C19 1,478 UGT2B7 146 P-gp 1,461 OCT2 647 OCT1 512 OAT3 642 OAT1 599 OATP1B3 706 OCT3 150 BSEP 402 OATP1B1 788 BCRP 699 MATE1 306 OAT2 145 MATE2-K 9	CES1b 4 CES1c 4 CES2 28 P-gp 1,537 BCRP 561 OATP1B1 406 OATP1B3 350	CYP1A2 701 CYP2B6 547

Drug as perpetrator

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Target	Modality	Activity	Metabolite
OATP1B1 803	inhibitor 3,277	no [IC50 110 uM]
OCT1 543	inhibitor 3,277	no [IC50 140 uM]	GS-829845 4
OCT1 543	inhibitor 3,277	no [IC50 151.6 uM]
OATP1B3 715	inhibitor 3,277	no [IC50 158 uM]	GS-829845 4
OATP1B3 715	inhibitor 3,277	no [IC50 168 uM]

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Drug as victim

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Target	Modality	Activity
CES2 28	substrate 3,367	major
CES1b 4	substrate 3,367	minor
CES1c 4	substrate 3,367	minor
BCRP 561	substrate 3,367	no
OATP1B1 406	substrate 3,367	no

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Tox targets

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Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1,647	inhibitor 1,626

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PubMed

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Title	Date	PubMed
Preclinical characterization of GLPG0634, a selective inhibitor of JAK1, for the treatment of inflammatory diseases.	2013 Oct 1	24006460

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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 MALEATE

Official Name

English

FILGOTINIB MALEATE [JAN]

Common Name

English

Filgotinib maleate [WHO-DD]

Common Name

English

CYCLOPROPANECARBOXAMIDE, N-(5-(4-((1,1-DIOXIDO-4-THIOMORPHOLINYL)METHYL)PHENYL)(1,2,4)TRIAZOLO(1,5-A)PYRIDIN-2-YL)-, (2Z)-2-BUTENEDIOATE (1:1)

Common Name

English

GS-6034

Code

English

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Classification Tree

Code System

Code

Designated/Withdrawn

FDA ORPHAN DRUG

588017

Designated/Withdrawn

FDA ORPHAN DRUG

604517

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Code System

Code

Type

Description

SMS_ID

100000182936

PRIMARY

PUBCHEM

131801100

PRIMARY

NCI_THESAURUS

C171929

PRIMARY

CAS

1802998-75-9

PRIMARY

EVMPD

SUB197232

PRIMARY

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ACTIVE MOIETY


					3XVL385Q0M

FILGOTINIB

SUBSTANCE RECORD


					JG8OB4UL9Y

FILGOTINIB MALEATE

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