FOSDENOPTERIN HYDROBROMIDE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C10H14N5O8P.BrH.2H2O
Molecular Weight	480.163
Optical Activity	UNSPECIFIED
Defined Stereocenters	4 / 4
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O.O.Br.NC1=NC2=C(N[C@@H]3[C@H](N2)O[C@@H]4COP(O)(=O)O[C@@H]4C3(O)O)C(=O)N1

InChI

InChIKey=GGLKTKQOHMCQHF-UNHNTEMGSA-N

InChI=1S/C10H14N5O8P.BrH.2H2O/c11-9-14-6-3(7(16)15-9)12-4-8(13-6)22-2-1-21-24(19,20)23-5(2)10(4,17)18;;;/h2,4-5,8,12,17-18H,1H2,(H,19,20)(H4,11,13,14,15,16);1H;2*1H2/t2-,4-,5+,8-;;;/m1.../s1

HIDE SMILES / InChI

Molecular Formula	C10H14N5O8P
Molecular Weight	363.2206
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	4 / 4
E/Z Centers	0
Optical Activity	UNSPECIFIED

Molecular Formula	BrH
Molecular Weight	80.912
Charge	0
Count

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

Molecular Formula	H2O
Molecular Weight	18.0153
Charge	0
Count

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

Description
Sources: https://pubmed.ncbi.nlm.nih.gov/33909276|https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/214018s000lbl.pdf

Fosdenopterin (NulibryTM) is a synthetic cyclic pyranopterin monophosphate that is being developed by Origin Biosciences (a subsidiary of BridgeBio Pharma) for the treatment of molybdenum cofactor deficiency (MoCD) type A. Patients with MoCD Type A have mutations in the MOCS1 gene leading to deficient MOCS1A/B dependent synthesis of the intermediate substrate, cPMP. Substrate replacement therapy with NULIBRY provides an exogenous source of cPMP, which is converted to molybdopterin. Molybdopterin is then converted to molybdenum cofactor, which is needed for the activation of molybdenum-dependent enzymes, including sulfite oxidase (SOX), an enzyme that reduces levels of neurotoxic sulfites. Fosdenopterin was approved by the US FDA in February 2021 for use in reducing the risk of mortality in paediatric and adult patients with MoCD type A.

CNS Activity

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Molybdopterin synthase catalytic subunit 3 Target ID: O96007 Gene ID: 4338.0 Gene Symbol: MOCS2 Target Organism: Homo sapiens (Human) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/214018s000lbl.pdf	Substrate 661

Conditions

Condition	Modality	Targets	Highest Phase	Product
molybdenum cofactor deficiency Type A 3 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/214018s000lbl.pdf	Primary		Approved 8583	NULIBRY Approved Use NULIBRY is cyclic pyranopterin monophosphate (cPMP) indicated to reduce the risk of mortality in patients with molybdenum cofactor deficiency (MoCD) Type A. Launch Date 2021

C_max

Value	Dose	Analyte	Population
285 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214018Orig1s000IntegratedR.pdf#page=93	0.075 mg/kg single, intravenous dose: 0.075 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	CYCLIC PYRANOPTERIN MONOPHOSPHATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
873 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214018Orig1s000IntegratedR.pdf#page=93	0.25 mg/kg single, intravenous dose: 0.25 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	CYCLIC PYRANOPTERIN MONOPHOSPHATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
2800 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214018Orig1s000IntegratedR.pdf#page=93	0.68 mg/kg single, intravenous dose: 0.68 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	CYCLIC PYRANOPTERIN MONOPHOSPHATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
523 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214018Orig1s000IntegratedR.pdf#page=93	0.075 mg/kg single, intravenous dose: 0.075 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	CYCLIC PYRANOPTERIN MONOPHOSPHATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
1790 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214018Orig1s000IntegratedR.pdf#page=93	0.25 mg/kg single, intravenous dose: 0.25 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	CYCLIC PYRANOPTERIN MONOPHOSPHATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
5960 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214018Orig1s000IntegratedR.pdf#page=93	0.68 mg/kg single, intravenous dose: 0.68 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	CYCLIC PYRANOPTERIN MONOPHOSPHATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
1.22 h OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214018Orig1s000IntegratedR.pdf#page=93	0.075 mg/kg single, intravenous dose: 0.075 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	CYCLIC PYRANOPTERIN MONOPHOSPHATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
1.67 h OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214018Orig1s000IntegratedR.pdf#page=93	0.25 mg/kg single, intravenous dose: 0.25 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	CYCLIC PYRANOPTERIN MONOPHOSPHATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
1.64 h OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214018Orig1s000IntegratedR.pdf#page=93	0.68 mg/kg single, intravenous dose: 0.68 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	CYCLIC PYRANOPTERIN MONOPHOSPHATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
87.6% OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214018Orig1s000IntegratedR.pdf#page=29 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214018Orig1s000IntegratedR.pdf#page=186			CYCLIC PYRANOPTERIN MONOPHOSPHATE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
1300 ug/kg/day 1 times / day multiple, intravenous Studied dose Dose: 1300 ug/kg/day, 1 times / day Route: intravenous Route: multiple Dose: 1300 ug/kg/day, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214018Orig1s000IntegratedR.pdf	unhealthy, NEWBORN\|CHILD Health Status: unhealthy Age Group: NEWBORN\|CHILD Sex: M+F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214018Orig1s000IntegratedR.pdf	Disc. AE: Adverse event, Adverse event... Other AEs: Respiratory tract infection, Pyrexia... AEs leading to discontinuation/dose reduction: Adverse event (0%) Adverse event (0%) Varicella (Serious, 1 pt) Stomatitis (Serious, 1 pt) Staphylococcal sepsis (Serious, 1 pt) Staphylococcal infection (Serious, 1 pt) Respiratory distress (Serious, 1 pt) Respiratory syncytial virus pneumonitis (Serious, 1 pt) Pleural effusion (Serious, 1 pt) Necrotizing colitis (Serious, 1 pt) Myoclonus (Serious, 1 pt) Irritability (Serious, 1 pt) Febrile infection (Serious, 1 pt) Other AEs: Respiratory tract infection (Serious, 2 patients) Pyrexia (Serious, 2 patients) Device issue (Serious, 2 patients) Device moved (Serious, 2 patients) Device related infection (Serious, 3 patients) Device related sepsis (Serious, 2 patients) Sepsis (Serious, 2 patients) Respiratory tract infection (Serious, 1 patient) Infection (Serious, 1 pt) Upper resp tract infection (Serious, 1 pt) Subdural effusion (Serious, 1 pt) Device leakage (Serious, 1 pt) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214018Orig1s000IntegratedR.pdf

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
	substrate 1193 inducer 440 inhibitor 2438	inhibitor 2507 substrate 1388	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
BCRP 910 CYP2B6 926 OATP1B3 961 CYP2C19 2057 OCT2 779 OATP1B1 1079 CYP3A4/5 296 OAT1 725 CYP1A2 2153 P-gp 1741 CYP2C8 1057 MATE2-K 77 MATE1 415 OAT3 747 Cav1.2 58 Nav1.5 116	CYP1A2 1197 CYP2B6 776 CYP2C8 810 BCRP 697 OAT3 391 OCT2 434 OATP1B1 503 CYP2C19 1119 MATE2-K 33 CYP3A4/5 91 OAT1 395 P-gp 2052 OATP1B3 435 MATE1 182	CYP1A2 832 CYP3A4/5 133 CYP2C19 329 CYP2C8 198 CYP2B6 669

Drug as perpetrator

Target	Modality	Activity
BCRP 985	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214018Orig1s000IntegratedR.pdf#page=30 Page: 30 \| 66 \| 75 \| 91	no [IC50 >200 uM]
MATE1 416	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214018Orig1s000IntegratedR.pdf#page=30 Page: 30 \| 66 \| 75 \| 91	no [IC50 >200 uM]
OAT3 749	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214018Orig1s000IntegratedR.pdf#page=30 Page: 30 \| 66 \| 75 \| 91	no [IC50 >200 uM]
OATP1B1 1095	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214018Orig1s000IntegratedR.pdf#page=30 Page: 30 \| 66 \| 75 \| 91	no [IC50 >200 uM]
OATP1B3 970	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214018Orig1s000IntegratedR.pdf#page=30 Page: 30 \| 66 \| 75 \| 91	no [IC50 >200 uM]
OCT2 782	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214018Orig1s000IntegratedR.pdf#page=30 Page: 30 \| 66 \| 75 \| 91	no [IC50 >200 uM]
P-gp 1932	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214018Orig1s000IntegratedR.pdf#page=30 Page: 30 \| 66 \| 75 \| 91	no [IC50 >200 uM]
CYP1A2 2333	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214018Orig1s000IntegratedR.pdf#page=30 Page: 30 \| 66 \| 75	no [IC50 >500 uM]
CYP2B6 1160	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214018Orig1s000IntegratedR.pdf#page=30 Page: 30 \| 66 \| 75	no [IC50 >500 uM]
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214018Orig1s000IntegratedR.pdf#page=30 Page: 30 \| 66 \| 75	no [IC50 >500 uM]
CYP2C8 1117	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214018Orig1s000IntegratedR.pdf#page=30 Page: 30 \| 66 \| 75	no [IC50 >500 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214018Orig1s000IntegratedR.pdf#page=30 Page: 30 \| 66 \| 75	no [IC50 >500 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214018Orig1s000IntegratedR.pdf#page=30 Page: 30 \| 66 \| 75	no [IC50 >500 uM]
CYP3A4/5 357	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214018Orig1s000IntegratedR.pdf#page=30 Page: 30 \| 66 \| 75	no [IC50 >500 uM]
CYP1A2 2333	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214018Orig1s000IntegratedR.pdf#page=30 Page: 30 \| 66 \| 75 \| 90	no
CYP2B6 1160	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214018Orig1s000IntegratedR.pdf#page=30 Page: 30 \| 66 \| 75 \|90	no
CYP2C19 2141	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214018Orig1s000IntegratedR.pdf#page=30 Page: 30 \| 66	no
CYP2C8 1117	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214018Orig1s000IntegratedR.pdf#page=30 Page: 30 \| 66	no
CYP2C9 2497	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214018Orig1s000IntegratedR.pdf#page=30 Page: 30 \| 66	no
CYP3A4/5 357	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214018Orig1s000IntegratedR.pdf#page=30 Page: 30 \| 66 \| 75 \| 90	no
MATE2-K 77	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214018Orig1s000IntegratedR.pdf#page=30 Page: 30 \| 66 \| 75 \| 91	weak [Inhibition 200 uM]
OAT1 730	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214018Orig1s000IntegratedR.pdf#page=30 Page: 30 \| 66 \| 75	weak [Inhibition 200 uM]

Drug as victim

Target	Modality	Activity
BCRP 697	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214018Orig1s000IntegratedR.pdf#page=29 Page: 29 \| 66 \| 75	no
CYP1A2 1197	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214018Orig1s000IntegratedR.pdf#page=29 Page: 29.0	no
CYP2B6 776	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214018Orig1s000IntegratedR.pdf#page=29 Page: 29.0	no
CYP2C19 1119	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214018Orig1s000IntegratedR.pdf#page=29 Page: 29.0	no
CYP2C8 810	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214018Orig1s000IntegratedR.pdf#page=29 Page: 29.0	no
CYP2C9 1193	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214018Orig1s000IntegratedR.pdf#page=29 Page: 29.0	no
CYP2D6 1388	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214018Orig1s000IntegratedR.pdf#page=29 Page: 29.0	no
CYP3A4/5 91	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214018Orig1s000IntegratedR.pdf#page=29 Page: 29.0	no
MATE2-K 33	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214018Orig1s000IntegratedR.pdf#page=29 Page: 29 \| 66 \| 75	no
OAT1 395	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214018Orig1s000IntegratedR.pdf#page=29 Page: 29 \| 66 \| 75 \| 91	no
OAT3 391	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214018Orig1s000IntegratedR.pdf#page=29 Page: 29 \| 66 \| 75 \| 91	no
OATP1B1 503	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214018Orig1s000IntegratedR.pdf#page=29 Page: 29 \| 66 \| 75 \| 91	no
OATP1B3 435	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214018Orig1s000IntegratedR.pdf#page=29 Page: 29 \| 66 \| 75 \| 91	no
OCT2 434	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214018Orig1s000IntegratedR.pdf#page=29 Page: 29 \| 66 \| 75 \| 91	no
P-gp 2052	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214018Orig1s000IntegratedR.pdf#page=29 Page: 29 \| 66 \| 75 \| 91	no
MATE1 182	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214018Orig1s000IntegratedR.pdf#page=29 Page: 29 \| 66 \| 75	weak

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
Cav1.2 63	inhibitor 2237 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214018Orig1s000IntegratedR.pdf#page=74 Page: 74 \| 185
Nav1.5 119	inhibitor 2237 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214018Orig1s000IntegratedR.pdf#page=74 Page: 74 \| 185
hERG 2263	inhibitor 2237 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214018Orig1s000IntegratedR.pdf#page=74 Page: 74 \| 185

PubMed

Title	Date	PubMed
Regulatory news: Nulibry (fosdenopterin) approved to reduce the risk of mortality in patients with molybdenum cofactor deficiency type A: FDA approval summary.	2021-09	34337775
Fosdenopterin: First Approval.	2021-06	33909276

Patents

Sample Use Guides

In Vivo Use Guide

Administer as an intravenous infusion once daily at a rate of 1.5 mL/minute with non-DEHP tubing with a 0.2 micron filter. Volumes below 2 mL may require syringe administration through slow intravenous push. Initial dosage (preterm neonates): 0.4 mg/kg once daily; Initial dosage (term neonates): 0.55 mg/kg once daily; Month 1 (preterm neonates): 0.7 mg/kg once daily; Month 1 (term neonates): 0.75 mg/kg once daily; Month 3 (preterm neonates): 0.9 mg/kg once daily; Month 3 (term neonates): 0.9 mg/kg once daily.

Route of Administration: Intravenous

In Vitro Use Guide

Fosdenopterin had no inhibitory effect on a variety of ion channels tested in an in vitro panel, with IC50 values >300uM.

Substance Class	Chemical Created by `admin` on `Wed Apr 02 13:40:18 GMT 2025` Edited by `admin` on `Wed Apr 02 13:40:18 GMT 2025`
Record UNII	X41B5W735T
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

NULIBRY

Preferred Name

English

FOSDENOPTERIN HYDROBROMIDE

Official Name

English

ALXN-1101 HYDROBROMIDE DIHYDRATE

Code

English

FOSDENOPTERIN HYDROBROMIDE [USAN]

Common Name

English

CYCLIC PYRANOPTERIN MONOPHOSPHATE MONOHYDROBROMIDE DIHYDRATE

Common Name

English

FOSDENOPTERIN HYDROBROMIDE [ORANGE BOOK]

Common Name

English

FOSDENOPTERIN HYDROBROMIDE DIHYDRATE

Common Name

English

1,3,2-DIOXAPHOSPHORINO(4',5':5,6)PYRANO(3,2-G)PTERIDIN-10(4H)-ONE, 8-AMINO-4A,5A,6,9,11,11A,12,12A-OCTAHYDRO-2,12,12-TRIHYDROXY-, 2-OXIDE, HYDROBROMIDE, HYDRATE (1:1:2), (4AR,5AR,11AR,12AS)-

Systematic Name

English

Fosdenopterin hydrobromide dihydrate [WHO-DD]

Common Name

English

Code System Code Type Description

NCI_THESAURUS

C174941