DIMETHYL FUMARATE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C6H8O4
Molecular Weight	144.1253
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC(=O)\C=C\C(=O)OC

InChI

InChIKey=LDCRTTXIJACKKU-ONEGZZNKSA-N

InChI=1S/C6H8O4/c1-9-5(7)3-4-6(8)10-2/h3-4H,1-2H3/b4-3+

HIDE SMILES / InChI

Molecular Formula	C6H8O4
Molecular Weight	144.1253
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	1
Optical Activity	NONE

Description
Sources: http://onlinelibrary.wiley.com/doi/10.1002/047084289X.rd344/fullhttps://pubmed.ncbi.nlm.nih.gov/34057708|https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211855s000lbl.pdf|https://www.ema.europa.eu/en/documents/overview/vumerity-epar-medicine-overview_en.pdfhttps://www.ncbi.nlm.nih.gov/pubmed/12522577 | https://www.ncbi.nlm.nih.gov/pubmed/27614618 | https://www.ncbi.nlm.nih.gov/pubmed/20664170 | https://multiplesclerosisnewstoday.com/alks-8700-multiple-sclerosis/http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/204063s014lbl.pdf

Dimethyl fumarate (DMF) is the methyl ester of fumaric acid. DMF was initially recognized as a very effective hypoxic cell radiosensitizer. Later, DMF combined with three other fumaric acid esters (FAE) was licensed in Germany as oral therapy for psoriasis (trade name Fumaderm). Phase III clinical trials found that DMF (BG-12) successfully reduced relapse rate and increased time to progression of disability in multiple sclerosis (trade name Tecfidera). DMF is thought to have immunomodulatory properties without significant immunosuppression. The mechanism of action of dimethyl fumarate in multiple sclerosis is not well understood. It is thought to involve dimethyl fumarate degradation to its active metabolite monomethyl fumarate (MMF) then MMF up-regulates the Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway that is activated in response to oxidative stress. Dimethyl fumarate is marketed under the brand name Tecfidera.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
NRF2 pathway 7 Target ID: WP2884 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27614618	Activator 1447
pyroptosis 6 Target ID: GO:0070269 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26096886	Inhibitor 8504
Hydroxycarboxylic acid receptor 2 28 Target ID: CHEMBL4420 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20664170 \| http://en.pharmacodia.com/web/drug/1_5666.html	Activator 1447
Nuclear factor erythroid 2-related factor 2 15 Target ID: Q16236 Gene ID: 4780.0 Gene Symbol: NFE2L2 Target Organism: Homo sapiens (Human) Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/204063s014lbl.pdf	Activator 1447
Glutathione S-transferase 6 Target ID: Glutathione S-transferase Sources: https://www.ncbi.nlm.nih.gov/pubmed/1287182	Substrate 661

Conditions

Condition	Modality	Highest Phase	Product
Relapsing forms of multiple sclerosis 6 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/204063s014lbl.pdf	Secondary	Approved 8583	TECFIDERA Approved Use Indicated for the treatment of patients with relapsing forms of multiple sclerosis Launch Date 2013
Arthritis 87 Sources: https://www.ncbi.nlm.nih.gov/pubmed/28832396	Palliative	Preclinical	Unknown Approved Use Unknown
Multiple sclerosis 107 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204063Orig1s010.pdf	Primary	Approved 8583	TECFIDERA Approved Use TECFIDERA, dimethyl fumarate undergoes rapid presystemic hydrolysis by esterases and is converted to its active metabolite, monomethyl fumarate (MMF). TECFIDERA is indicated for the treatment of patients with relapsing forms of multiple sclerosis. Launch Date 2013
Ischemic stroke 35 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27614618	Preventing	Preclinical	Unknown Approved Use Unknown
Relapsing forms of multiple sclerosis 6 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211855s000lbl.pdf	Primary	Approved 8583	Vumerity Approved Use Indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults. Launch Date 2019
Unknown 2596

C_max

Value	Dose	Co-administered	Analyte	Population
1.57 μg/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211855Orig1s000ClinPharmR.pdf#page=10	462 mg single, oral dose: 462 mg route of administration: Oral experiment type: SINGLE co-administered:		MONOMETHYL FUMARATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
0.88 μg/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211855Orig1s000ClinPharmR.pdf#page=15	462 mg single, oral dose: 462 mg route of administration: Oral experiment type: SINGLE co-administered:		MONOMETHYL FUMARATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: HIGH-FAT
1.63 μg/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211855Orig1s000ClinPharmR.pdf#page=20	462 mg single, oral dose: 462 mg route of administration: Oral experiment type: SINGLE co-administered:		MONOMETHYL FUMARATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
0.955 μg/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211855Orig1s000ClinPharmR.pdf#page=21	462 mg single, oral dose: 462 mg route of administration: Oral experiment type: SINGLE co-administered:		MONOMETHYL FUMARATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: HIGH-FAT
0.9 μg/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211855Orig1s000ClinPharmR.pdf#page=23	462 mg single, oral dose: 462 mg route of administration: Oral experiment type: SINGLE co-administered: ALCOHOL	ALCOHOL	MONOMETHYL FUMARATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
1 μg/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211855Orig1s000ClinPharmR.pdf#page=23	462 mg single, oral dose: 462 mg route of administration: Oral experiment type: SINGLE co-administered: ALCOHOL	ALCOHOL	MONOMETHYL FUMARATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
0.6 μg/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211855Orig1s000ClinPharmR.pdf#page=23	462 mg single, oral dose: 462 mg route of administration: Oral experiment type: SINGLE co-administered: ALCOHOL	ALCOHOL	MONOMETHYL FUMARATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
2.11 mg/L DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211855s000lbl.pdf	462 mg 2 times / day multiple, oral dose: 462 mg route of administration: Oral experiment type: MULTIPLE co-administered:		MONOMETHYL FUMARATE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
1.87 mg/L DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204063lbl.pdf	240 mg 2 times / day multiple, oral dose: 240 mg route of administration: Oral experiment type: MULTIPLE co-administered:		MONOMETHYL FUMARATE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED

AUC

Value	Dose	Analyte	Population
3.57 μg × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211855Orig1s000ClinPharmR.pdf#page=10	462 mg single, oral dose: 462 mg route of administration: Oral experiment type: SINGLE co-administered:	MONOMETHYL FUMARATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
3.336 μg × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211855Orig1s000ClinPharmR.pdf#page=12	462 mg single, oral dose: 462 mg route of administration: Oral experiment type: SINGLE co-administered:	MONOMETHYL FUMARATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED
4.879 μg × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211855Orig1s000ClinPharmR.pdf#page=12	462 mg single, oral dose: 462 mg route of administration: Oral experiment type: SINGLE co-administered:	MONOMETHYL FUMARATE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED
4.939 μg × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211855Orig1s000ClinPharmR.pdf#page=12	462 mg single, oral dose: 462 mg route of administration: Oral experiment type: SINGLE co-administered:	MONOMETHYL FUMARATE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED
4.743 μg × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211855Orig1s000ClinPharmR.pdf#page=12	462 mg single, oral dose: 462 mg route of administration: Oral experiment type: SINGLE co-administered:	MONOMETHYL FUMARATE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED
2.83 μg × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211855Orig1s000ClinPharmR.pdf#page=15	462 mg single, oral dose: 462 mg route of administration: Oral experiment type: SINGLE co-administered:	MONOMETHYL FUMARATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: HIGH-FAT
3.09 μg × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211855Orig1s000ClinPharmR.pdf#page=20	462 mg single, oral dose: 462 mg route of administration: Oral experiment type: SINGLE co-administered:	MONOMETHYL FUMARATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
2.5 μg × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211855Orig1s000ClinPharmR.pdf#page=21	462 mg single, oral dose: 462 mg route of administration: Oral experiment type: SINGLE co-administered:	MONOMETHYL FUMARATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: HIGH-FAT
8.32 mg × h/L DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211855s000lbl.pdf	462 mg 2 times / day multiple, oral dose: 462 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MONOMETHYL FUMARATE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
8.21 mg × h/L DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204063lbl.pdf	240 mg 2 times / day multiple, oral dose: 240 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MONOMETHYL FUMARATE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED

T_1/2

Value	Dose	Co-administered	Analyte	Population
1 h OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211855Orig1s000ClinPharmR.pdf#page=8	single, oral		MONOMETHYL FUMARATE plasma	Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN
1 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204063lbl.pdf	240 mg 2 times / day multiple, oral dose: 240 mg route of administration: Oral experiment type: MULTIPLE co-administered:		MONOMETHYL FUMARATE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED

F_unbound

Value	Dose	Co-administered	Analyte	Population
75% OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211855Orig1s000ClinPharmR.pdf#page=8			MONOMETHYL FUMARATE plasma	Homo sapiens
64% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204063lbl.pdf	240 mg 2 times / day multiple, oral dose: 240 mg route of administration: Oral experiment type: MULTIPLE co-administered:		MONOMETHYL FUMARATE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED

Doses

Dose	Population	Adverse events
190 mg 2 times / day multiple, oral Highest studied dose Dose: 190 mg, 2 times / day Route: oral Route: multiple Dose: 190 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/210296s000lbl.pdf	unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/210296s000lbl.pdf	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/210296s000lbl.pdf
190 mg 2 times / day multiple, oral Highest studied dose Dose: 190 mg, 2 times / day Route: oral Route: multiple Dose: 190 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/32629403/	unhealthy, mean 37 years Health Status: unhealthy Age Group: mean 37 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/32629403/	Other AEs: Gastrointestinal disturbance... Other AEs: Gastrointestinal disturbance (53%) Sources: https://pubmed.ncbi.nlm.nih.gov/32629403/
462 mg 2 times / day multiple, oral Recommended Dose: 462 mg, 2 times / day Route: oral Route: multiple Dose: 462 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/31953790/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/31953790/	Disc. AE: Adverse event, Gastrointestinal adverse event... AEs leading to discontinuation/dose reduction: Adverse event (0.8%) Gastrointestinal adverse event (0.8%) Sources: https://pubmed.ncbi.nlm.nih.gov/31953790/
462 mg 2 times / day multiple, oral Recommended Dose: 462 mg, 2 times / day Route: oral Route: multiple Dose: 462 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/31680631/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/31680631/	Disc. AE: Adverse event, Gastrointestinal adverse event... AEs leading to discontinuation/dose reduction: Adverse event (5.6%) Gastrointestinal adverse event (0.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/31680631/
240 mg 2 times / day multiple, oral Studied dose Dose: 240 mg, 2 times / day Route: oral Route: multiple Dose: 240 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211855s000lbl.pdf	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211855s000lbl.pdf	Disc. AE: Gastrointestinal events, Elevated hepatic transaminases... AEs leading to discontinuation/dose reduction: Gastrointestinal events (4%) Elevated hepatic transaminases (<1%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211855s000lbl.pdf

AEs

AE	Significance	Dose	Population
Gastrointestinal disturbance	53%	190 mg 2 times / day multiple, oral Highest studied dose Dose: 190 mg, 2 times / day Route: oral Route: multiple Dose: 190 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/32629403/	unhealthy, mean 37 years Health Status: unhealthy Age Group: mean 37 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/32629403/
Adverse event	0.8% Disc. AE	462 mg 2 times / day multiple, oral Recommended Dose: 462 mg, 2 times / day Route: oral Route: multiple Dose: 462 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/31953790/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/31953790/
Gastrointestinal adverse event	0.8% Disc. AE	462 mg 2 times / day multiple, oral Recommended Dose: 462 mg, 2 times / day Route: oral Route: multiple Dose: 462 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/31953790/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/31953790/
Gastrointestinal adverse event	0.7% Disc. AE	462 mg 2 times / day multiple, oral Recommended Dose: 462 mg, 2 times / day Route: oral Route: multiple Dose: 462 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/31680631/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/31680631/
Adverse event	5.6% Disc. AE	462 mg 2 times / day multiple, oral Recommended Dose: 462 mg, 2 times / day Route: oral Route: multiple Dose: 462 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/31680631/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/31680631/
Gastrointestinal events	4% Disc. AE	240 mg 2 times / day multiple, oral Studied dose Dose: 240 mg, 2 times / day Route: oral Route: multiple Dose: 240 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211855s000lbl.pdf	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211855s000lbl.pdf
Elevated hepatic transaminases	<1% Disc. AE	240 mg 2 times / day multiple, oral Studied dose Dose: 240 mg, 2 times / day Route: oral Route: multiple Dose: 240 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211855s000lbl.pdf	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211855s000lbl.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252 inducer 1087	inhibitor 2438	inhibitor 2507

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C19 2057 P-gp 1741 BCRP 910 MATE1 415 CYP2C8 1057 CYP2B6 926 CYP3A5 136 CYP1A2 2153 MATE2-K 77 OAT1 725 OAT3 747 OCT2 779 CYP 110	CYP 303 BCRP 697 CYP450 59	P-gp 301 CYP2B6 669 CYP1A2 832 CYP 74

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
BCRP 985	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211855Orig1s000ClinPharmR.pdf#page=22 Page: 22.0	no
BCRP 985	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211855Orig1s000ClinPharmR.pdf#page=22 Page: 22.0	no	2-hydroxyethyl succinimide (HES, RDC-6567) 6
CYP 150	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/210296s000lbl.pdf#page=10 Page: 10.0	no
CYP 150	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/210296s000lbl.pdf#page=10 Page: 10.0	no
CYP1A2 2333	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211855Orig1s000ClinPharmR.pdf#page=22 Page: 22.0	no
CYP1A2 2333	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211855Orig1s000ClinPharmR.pdf#page=22 Page: 22.0	no
CYP2B6 1160	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211855Orig1s000ClinPharmR.pdf#page=22 Page: 22.0	no
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211855Orig1s000ClinPharmR.pdf#page=22 Page: 22.0	no
CYP2C8 1117	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211855Orig1s000ClinPharmR.pdf#page=22 Page: 22.0	no
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211855Orig1s000ClinPharmR.pdf#page=22 Page: 22.0	no
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211855Orig1s000ClinPharmR.pdf#page=22 Page: 22.0	no
CYP3A4 2633	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211855Orig1s000ClinPharmR.pdf#page=22 Page: 22.0	no
CYP3A4 2633	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211855Orig1s000ClinPharmR.pdf#page=22 Page: 22.0	no
CYP3A5 201	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211855Orig1s000ClinPharmR.pdf#page=22 Page: 22.0	no
MATE1 416	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211855Orig1s000ClinPharmR.pdf#page=22 Page: 22.0	no	2-hydroxyethyl succinimide (HES, RDC-6567) 6
MATE2-K 77	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211855Orig1s000ClinPharmR.pdf#page=22 Page: 22.0	no	2-hydroxyethyl succinimide (HES, RDC-6567) 6
OAT1 730	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211855Orig1s000ClinPharmR.pdf#page=22 Page: 22.0	no	2-hydroxyethyl succinimide (HES, RDC-6567) 6
OAT3 749	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211855Orig1s000ClinPharmR.pdf#page=22 Page: 22.0	no	2-hydroxyethyl succinimide (HES, RDC-6567) 6
OCT2 782	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211855Orig1s000ClinPharmR.pdf#page=22 Page: 22.0	no	2-hydroxyethyl succinimide (HES, RDC-6567) 6
P-gp 1932	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/210296s000lbl.pdf#page=10 Page: 10.0	no
P-gp 1932	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211855Orig1s000ClinPharmR.pdf#page=22 Page: 22.0	no
P-gp 1932	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/210296s000lbl.pdf#page=10 Page: 10.0	no
CYP2B6 1160	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211855Orig1s000ClinPharmR.pdf#page=22 Page: 22.0	np
P-gp 1932	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211855Orig1s000ClinPharmR.pdf#page=22 Page: 22.0	yes [Inhibition 100 uM]		no (co-administration study) Comment: Decreased digoxin Cmax, AUClast, and AUCinf approximately 10% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211855Orig1s000ClinPharmR.pdf#page=22 Page: 22.0

Drug as victim

Target	Modality	Activity	Metabolite
BCRP 697	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211855Orig1s000ClinPharmR.pdf#page=22 Page: 22.0	no
CYP 303	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211855Orig1s000ClinPharmR.pdf#page=8 Page: 8.0	no	Monomethyl fumarate 6
CYP450 59	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/210296Orig1s000ClinPharmR.pdf#page=8 Page: 8.0	no

Sourcing

Vendor/Aggregator	ID	URL
3B Scientific (Wuhan) Corp	3B4-0303	http://www.3bsc.com/index/pro_info.php?id=18151
3B Scientific (Wuhan) Corp	3B4-2852	http://www.3bsc.com/index/pro_info.php?id=77486
Aaron Chemicals	AR002URG	http://www.aaronchem.com/2756-87-8
abcr GmbH	AB503712	http://www.abcr.com/shop/en/AB503712
abcr GmbH	AB558870	http://www.abcr.com/shop/en/AB558870
Achemtek	0104-021727	http://www.achemtek.com/2756-87-8
AK Scientific, Inc. (AKSCI)	O997	http://www.aksci.com/item_detail.php?cat=O997
Alfa Chemistry	AP2756878	https://reagents.alfa-chemistry.com/product/mono-methyl-fumarate-cas-2756-87-8-9093.html
Alichem	490019201	http://www.alichem.com/en/products/2756-87-8.html
Ambeed	A983659	https://www.ambeed.com/products/2756-87-8.html
Ambinter	Amb10071357	http://www.ambinter.com/reference/10071357
ApexBio Technology	B7674	http://www.apexbt.com/mmf.html
Aurora Fine Chemicals LLC	A01.295.615	http://online.aurorafinechemicals.com/info?ID=A01.295.615
Aurum Pharmatech LLC	M-3444	http://www.Aurumpharmatech.com/Product/ProductDetails/M_3444
Avantor Inc	TCM2413-5G	https://us.vwr.com/store/product/16813484/fumaric-acid-monomethyl-ester-98-0-by-gc
BioChemPartner	BCP18454	http://www.biochempartner.com/2756-87-8-BCP18454
BioSynth	J-017996	https://www.biosynth.com/en/products/all-products/products/J-017996.html
BioSynth	J-522708	https://www.biosynth.com/en/products/all-products/products/J-522708.html
BLD Pharm	BD00941719	http://www.bldpharm.com/products/2756-87-8.html
BLD Pharm	BD140326	http://www.bldpharm.com/products/2756-87-8.html
Chem Scene	CS-0026484	http://www.chemscene.com/2756-87-8.html
ChemMol	99067199	http://www.chemmol.com/chemmol/99067199.html
Chemspace	CSSB00011216927	https://chem-space.com/CSSB00011216927
CSNpharm	CSN22981	https://www.csnpharm.com/products/mmf.html
DC Chemicals	DC33842	http://www.dcchemicals.com//product_show-Monomethyl_Fumarate.html
eNovation Chemicals	D382932	http://www.enovationchem.com/productDetails.asp?productID=D382932
eNovation Chemicals	D533508	https://www.enovationchem.com/ProductDetails.asp?ProductID=D533508
eNovation Chemicals	D695687	https://www.enovationchem.com/ProductDetails.asp?ProductID=D695687
Hairui	MOJB01402	http://www.hairuichem.com/en/product/2756-87-8.html
iChemical	EBD2637923	http://www.ichemical.com/products/2756-87-8.html?utm_source=PubChem&utm_medium=website&utm_campaign=product%20catalogs
Lab Network	LN01310370	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01310370
LGC Standards	MM0352.03-0025	https://www.lgcstandards.com/US/en/p/MM0352.03-0025
MedChem Express	HY-103252	https://www.medchemexpress.com/monomethyl-fumarate.html
MuseChem	R058046	https://www.musechem.com/product/R058046.html
Oakwood	102026	http://www.oakwoodchemical.com/ProductsList.aspx?CategoryID=-2&txtSearch=170495&ExtHyperLink=1
Oakwood	94823	http://www.oakwoodchemical.com/ProductsList.aspx?CategoryID=-2&txtSearch=79997&ExtHyperLink=1
OChem	4292	http://www.ocheminc.com/index.php?act=psearch&pid=56M878
Selleck Chemicals	S6889	http://www.selleckchem.com/products/monomethyl-fumarate.html
Sigma-Aldrich	651419_ALDRICH	https://www.sigmaaldrich.com/catalog/product/aldrich/651419?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sigma-Aldrich	92571_SIAL	https://www.sigmaaldrich.com/catalog/product/sial/92571?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Smolecule	S536016	http://www.smolecule.com/products/s536016
Smolecule	S759551	https://www.smolecule.com/products/s759551
TCI (Tokyo Chemical Industry)	M2413	http://www.tcichemicals.com/eshop/en/us/commodity/M2413/index.html
THE BioTek	bt-275065	https://www.thebiotek.com/product/inhibitors/bt-275065
Tocris	4511	https://www.tocris.com/products/mmf_4511
VladaChem	VL278632-1G	https://www.vladachem.com/product.php?products=2756-87-8

PubMed

Title	Date	PubMed
Efficacy and Safety Outcomes with Diroximel Fumarate After Switching from Prior Therapies or Continuing on DRF: Results from the Phase 3 EVOLVE-MS-1 Study.	2022-04	35211872
Diroximel Fumarate in Relapsing Forms of Multiple Sclerosis: A Profile of Its Use.	2021-06	34057708
Diroximel fumarate (DRF) in patients with relapsing-remitting multiple sclerosis: Interim safety and efficacy results from the phase 3 EVOLVE-MS-1 study.	2020-11	31680631
Diroximel fumarate to treat multiple sclerosis.	2020-07	32648853
Diroximel Fumarate Demonstrates an Improved Gastrointestinal Tolerability Profile Compared with Dimethyl Fumarate in Patients with Relapsing-Remitting Multiple Sclerosis: Results from the Randomized, Double-Blind, Phase III EVOLVE-MS-2 Study.	2020-02	31953790
Monomethyl fumarate treatment impairs maturation of human myeloid dendritic cells and their ability to activate T cells.	2019-01	29106333
Dual action by fumaric acid esters synergistically reduces adhesion to human endothelium.	2018-12	28984166
Dimethyl fumarate treatment alters NK cell function in multiple sclerosis.	2018-02	29108094
Multiple mechanisms of dimethyl fumarate in amyloid β-induced neurotoxicity in human neuronal cells.	2018-02	28990726
Dimethyl fumarate influences innate and adaptive immunity in multiple sclerosis.	2018-01	28958667
Monomethyl fumarate inhibits pain behaviors and amygdala activity in a rat arthritis model.	2017-12	28832396
Bioanalysis of monomethyl fumarate in human plasma by a sensitive and rapid LC-MS/MS method and its pharmacokinetic application.	2017-11-30	28873360
Role of Nuclear Factor (Erythroid-Derived 2)-Like 2 Signaling for Effects of Fumaric Acid Esters on Dendritic Cells.	2017	29312359
Recent advances in understanding NRF2 as a druggable target: development of pro-electrophilic and non-covalent NRF2 activators to overcome systemic side effects of electrophilic drugs like dimethyl fumarate.	2017	29263788
Small molecule activators of the Nrf2-HO-1 antioxidant axis modulate heme metabolism and inflammation in BV2 microglia cells.	2013-10	23942037
Structure-activity comparison of the cytotoxic properties of diethyl maleate and related molecules: identification of diethyl acetylenedicarboxylate as a thiol cross-linking agent.	2011-01-14	21105742
DMF inhibits PDGF-BB induced airway smooth muscle cell proliferation through induction of heme-oxygenase-1.	2010-10-20	20961405
Molecular mechanisms of Nrf2-mediated antioxidant response.	2009-02	18618599
The psoriasis drug monomethylfumarate is a potent nicotinic acid receptor agonist.	2008-10-31	18722346
Effect of inducers of DT-diaphorase on the haemolytic activity and nephrotoxicity of 2-amino-1,4-naphthoquinone in rats.	2005-08-15	16045903
Enhanced cytotoxicity of bioreductive antitumor agents with dimethyl fumarate in human glioblastoma cells.	2005-02	15655414
Identification of anti-inflammatory drugs according to their capacity to suppress type-1 and type-2 T cell profiles.	2004-12	15663561
Antifungal properties of 2-bromo-3-fluorosuccinic acid esters and related compounds.	1977-04	321785

Patents

Sample Use Guides

In Vivo Use Guide

Male and female weanling Sprague-Dawley rats were used for activity evaluation. The experiment was a three-factor, two-bytwo- by-two design with two dietary variables; arsenic as Na2HAsO4 7H20, 0 or 0.5 mkg/g, and DEM (Dimethyl maleate), 0 or 0.25%; gender was the third variable. The rats were fed their respective diets for 10 wk, fasted for 16 h, weighed, then decapitated subsequent to ether anesthesia and a cardiac blood draw with a heparin-coated syringe and needle.

Route of Administration: Oral

In Vitro Use Guide

Hepatic microsomal fractions were isolated from Male, Sprague-Dawley rats. Reaction mixtures contained 50 mkM of phosphate buffer (p11 7.4)) 15 mkM of magnesium chloride, 10 mkM of DL-isocitric acid, 1 mkM of NADP+, 1 unit of isocitrate dehydrogenase (Sigma), varying amounts of substrates and diethyl maleate and approximately 3 mg of microsomal protein in a final volume of 3.0 ml. Reaction mixtures were incubated for 15 min at 37°C.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:20:10 GMT 2025` Edited by `admin` on `Mon Mar 31 18:20:10 GMT 2025`
Record UNII	FO2303MNI2
Record Status	`Validated (UNII)`
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Name

Type

Language

DIMETHYL FUMARATE

Official Name

English

FUMARIC ACID DIMETHYL ESTER

Preferred Name

English

FAG-201

Code

English

NSC-167432

Code

English

BG-00012

Code

English

BG 12

Code

English

2-BUTENEDIOIC ACID, (2E)-, DIMETHYL ESTER

Common Name

English

FP187

Code

English

DIMETHYL FUMARATE [JAN]

Common Name

English

BG00012

Code

English

DIMETHYL FUMARATE [MI]

Common Name

English

LAS-41008

Code

English

DIMETHYL FUMARATE [ORANGE BOOK]

Common Name

English

AZL-O-211089

Code

English

LAS41008

Code

English

BG 00012

Code

English

DIMETHYL FUMARATE [HSDB]

Common Name

English

DIMETHYL FUMARATE [USAN]

Common Name

English

NSC-25942

Code

English

TECFIDERA

Brand Name

English

FP-187

Code

English

AZL O 211089

Code

English

BG-12

Code

English

PANACLAR

Brand Name

English

DIMETHYL FUMARATE [VANDF]

Common Name

English

Dimethyl (2E)-but-2-enedioate

Systematic Name

English

AZL-0211089

Code

English

Dimethyl fumarate [WHO-DD]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C29708