Fosdenopterin (WHO-11150; ALXN 1101; Precursor Z; BBP-870; Nulibry) is a synthetic cyclic pyranopterin monophosphate (cPMP) that has been approved in 2021 as a medication to reduce the risk of mortality in patients with molybdenum cofactor deficiency Type A, which is a rare genetic disease.

Physicochemical Properties

Molecular Formula	C10H14N5O8P
Molecular Weight	363.22
Exact Mass	363.058
CAS #	150829-29-1
Related CAS #	2301083-34-9 (HBr);150829-29-1;
PubChem CID	135463437
Appearance	Typically exists as solid at room temperature
LogP	-4
Hydrogen Bond Donor Count	7
Hydrogen Bond Acceptor Count	11
Rotatable Bond Count	0
Heavy Atom Count	24
Complexity	722
Defined Atom Stereocenter Count	4
SMILES	NC1=NC(=O)C2NC3C(NC=2N1)OC1COP(OC1C3(O)O)(O)=O
InChi Key	CZAKJJUNKNPTTO-UHFFFAOYSA-N
InChi Code	InChI=1S/C10H14N5O8P/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)
Chemical Name	8-amino-2,12,12-trihydroxy-4a,5a,6,7,11,11a,12,12a-octahydro-[1,3,2]dioxaphosphinino[4',5'
Synonyms	Fosdenopterin ALXN1101 WHO11150 Nulibry ALXN-1101 WHO 11150ALXN 1101 WHO-11150
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ADME/Pharmacokinetics	Absorption, Distribution and Excretion In healthy adult subjects, the observed Cmax and AUC0-inf following the intravenous administration of 0.68 mg/kg (0.76x the maximum recommended dose) were 2800 ng/mL and 5960 ng*h/mL, respectively. Both Cmax and AUC0-inf appear to increase proportionally with increasing doses. Renal clearance of fosdenopterin accounts for approximately 40% of total clearance. The volume of distribution of fosdenopterin is approximately 300 mL/kg. Total body clearance of fosdenopterin ranges from 167 to 195 mL/h/kg. Metabolism / Metabolites Fosdenopterin metabolism occurs mainly via non-enzymatic degradation into Compound Z, which is a pharmacologically inactive product of endogenous cyclic pyranopterin monophosphate. Biological Half-Life The mean half-life of fosdenopterin ranges from 1.2 to 1.7 hours.
Toxicity/Toxicokinetics	Protein Binding Plasma protein binding ranges from 6 to 12%, though the specific proteins to which fosdenopterin binds have not been elucidated.
References	Fosdenopterin: First Approval. Drugs. 2021;81(8):953-956.
Additional Infomation	Pharmacodynamics Fosdenopterin replaces an intermediate substrate in the synthesis of molybdenum cofactor, a compound necessary for the activation of several molybdenum-dependent enzymes including sulfite oxidase (SOX). Given that SOX is responsible for detoxifying sulfur-containing acids and sulfites such as S-sulfocysteine (SSC), urinary levels of SSC can be used as a surrogate marker of efficacy for fosdenopterin. Long-term therapy with fosdenopterin has been shown to result in a sustained reduction in urinary SSC normalized to creatinine. Animal studies have identified a potential risk of phototoxicity in patients receiving fosdenopterin - these patients should avoid or minimize exposure to sunlight and/or artificial UV light. If sun exposure is necessary, use protective clothing, hats, and sunglasses, in addition to seeking shade whenever practical. Consider the use of a broad-spectrum sunscreen in patients 6 months of age or older.

Solubility Data

Solubility (In Vitro)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.7532 mL	13.7658 mL	27.5315 mL
	5 mM	0.5506 mL	2.7532 mL	5.5063 mL
	10 mM	0.2753 mL	1.3766 mL	2.7532 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.