ARFOLITIXORIN

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C20H23N7O6
Molecular Weight	457.4399
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NC1=NC(=O)C2=C(NC[C@@H]3CN(CN23)C4=CC=C(C=C4)C(=O)N[C@@H](CCC(O)=O)C(O)=O)N1

InChI

InChIKey=QYNUQALWYRSVHF-OLZOCXBDSA-N

InChI=1S/C20H23N7O6/c21-20-24-16-15(18(31)25-20)27-9-26(8-12(27)7-22-16)11-3-1-10(2-4-11)17(30)23-13(19(32)33)5-6-14(28)29/h1-4,12-13H,5-9H2,(H,23,30)(H,28,29)(H,32,33)(H4,21,22,24,25,31)/t12-,13+/m1/s1

HIDE SMILES / InChI

Molecular Formula	C20H23N7O6
Molecular Weight	457.4399
Charge	0
Count

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

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/10720211 | https://clinicaltrials.gov/ct2/show/NCT02244632 | https://isofolmedical.com/arfolitixorin/ | https://www.ncbi.nlm.nih.gov/pubmed/26189513

METHYLENETETRAHYDROFOLIC ACID, L-(+), an endogenous biomodulator that was developed under the brand name modufolin or arfolitixorin by the Isofol Medical. Arfolitixorin is developed to increase the efficacy of standard of care chemotherapy for advanced colorectal cancer. This drug is currently being studied in a global phase 3 clinical trial. Besides, the drug successfully completed phase II as rescue therapy for osteosarcoma. 21 May 2019 Isofol Medical has received clinical patent protection for the arfolitixorinin USA. It relates to a method of increasing blood concentration of deoxyuridine, a blood biomarker for inhibition of tumor growth in human cancer treatment.

Approval Year

C_max

Value	Dose	Co-administered	Analyte	Population
2860 ng/mL EXPERIMENT https://www.sciencedirect.com/science/article/pii/S2059702922002198	30 mg/m² single, intravenous dose: 30 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: FLUOROURACIL	FLUOROURACIL	METHYLENETETRAHYDROFOLIC ACID, L-( )- plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
4410 ng/mL EXPERIMENT https://www.sciencedirect.com/science/article/pii/S2059702922002198	60 mg/m² single, intravenous dose: 60 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: FLUOROURACIL	FLUOROURACIL	METHYLENETETRAHYDROFOLIC ACID, L-( )- plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
21200 ng/mL EXPERIMENT https://www.sciencedirect.com/science/article/pii/S2059702922002198	240 mg/m² single, intravenous dose: 240 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: FLUOROURACIL	FLUOROURACIL	METHYLENETETRAHYDROFOLIC ACID, L-( )- plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
39.4 pmol/mL EXPERIMENT https://link.springer.com/article/10.2165/11532990-000000000-00000	416 μg/m² single, intravenous dose: 416 μg/m² route of administration: Intravenous experiment type: SINGLE co-administered: FLUOROURACIL	FLUOROURACIL	METHYLENETETRAHYDROFOLIC ACID, L-( )- plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
1460 ng × h/mL EXPERIMENT https://www.sciencedirect.com/science/article/pii/S2059702922002198	30 mg/m² single, intravenous dose: 30 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: FLUOROURACIL	FLUOROURACIL	METHYLENETETRAHYDROFOLIC ACID, L-( )- plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2370 ng × h/mL EXPERIMENT https://www.sciencedirect.com/science/article/pii/S2059702922002198	60 mg/m² single, intravenous dose: 60 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: FLUOROURACIL	FLUOROURACIL	METHYLENETETRAHYDROFOLIC ACID, L-( )- plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
10600 ng × h/mL EXPERIMENT https://www.sciencedirect.com/science/article/pii/S2059702922002198	240 mg/m² single, intravenous dose: 240 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: FLUOROURACIL	FLUOROURACIL	METHYLENETETRAHYDROFOLIC ACID, L-( )- plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
210 pmol × h/mL EXPERIMENT https://link.springer.com/article/10.2165/11532990-000000000-00000	416 μg/m² single, intravenous dose: 416 μg/m² route of administration: Intravenous experiment type: SINGLE co-administered: FLUOROURACIL	FLUOROURACIL	METHYLENETETRAHYDROFOLIC ACID, L-( )- plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

PubMed

Title	Date	PubMed
Molecular biology of 5,10-methylenetetrahydrofolate reductase.	2000 Jan-Feb	10720211
Formaldehyde-detoxifying role of the tetrahydromethanopterin-linked pathway in Methylobacterium extorquens AM1.	2003 Dec	14645276
Phase 1 dose de-escalation trial of the endogenous folate [6R]-5,10-methylene tetrahydrofolate in combination with fixed-dose pemetrexed as neoadjuvant therapy in patients with resectable rectal cancer.	2015 Oct	26189513

Sample Use Guides

In Vivo Use Guide

IV injection every second week for 8 weeks 30 to 240 mg/m2

Route of Administration: Intravenous

Substance Class	Chemical Created by `admin` on `Mon Mar 31 21:34:58 GMT 2025` Edited by `admin` on `Mon Mar 31 21:34:58 GMT 2025`
Record UNII	Z8R4A37V9Q
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

MODUFOLIN

Preferred Name

English

ARFOLITIXORIN

Official Name

English

ARFOLITIXORIN [USAN]

Common Name

English

(6R)-5,10-METHYLENETETRAHYDROFOLATE

Common Name

English

6R-MTHF

Common Name

English

D-N5,N10-METHYLENE-L-TETRAHYDROFOLIC ACID

Common Name

English

5,10-METHYLENE-(6R)-TETRAHYDROFOLIC ACID

Common Name

English

(6R)-5,10-METHYLENE-5,6,7,8-TETRAHYDROFOLIC ACID

Common Name

English

Arfolitixorin [WHO-DD]

Common Name

English

METHYLENETETRAHYDROFOLIC ACID, L-(+)-

Common Name

English

ISO-901

Code

English

L-(+)-METHYLENETETRAHYDROFOLIC ACID

Common Name

English

arfolitixorin [INN]

Common Name

English

N-(4-((6AR)-3-AMINO-1-OXO-1,2,5,6,6A,7-HEXAHYDROIMIDAZO(1,5-F)PTERIDIN-8(9H)- YL)BENZOYL)-L-GLUTAMIC ACID

Systematic Name

English

L-GLUTAMIC ACID, N-(4-((6AR)-3-AMINO-1,2,5,6,6A,7-HEXAHYDRO-1-OXOIMIDAZO(1,5-F)PTERIDIN-8(9H)-YL)BENZOYL)-

Systematic Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

189304