Stannsoporfin

Identification

Name
Stannsoporfin
Accession Number
DB04912
Type
Small Molecule
Groups
Investigational
Description

Stannsoporfin is a competitive heme oxygenase (HO) inhibitor being developed by InfaCare, a subsidiary of WellSpring Pharmaceuticals, for the prevention of hyperbilirubinemia in infants at risk of developing jaundice.

Structure
Thumb
Synonyms
  • SnMP
  • Tin (IV) mesoporphyrin IX dichloride
  • tin-mesoporphyrin
External IDs
B-992
International/Other Brands
Stanate
Categories
UNII
0KAE1U0G7Q
CAS number
106344-20-1
Weight
Average: 754.3
Monoisotopic: 754.113563
Chemical Formula
C34H36Cl2N4O4Sn
InChI Key
LLDZJTIZVZFNCM-UHEVNVKKSA-J
InChI
InChI=1S/C34H38N4O4.2ClH.Sn/c1-7-21-17(3)25-13-26-19(5)23(9-11-33(39)40)31(37-26)16-32-24(10-12-34(41)42)20(6)28(38-32)15-30-22(8-2)18(4)27(36-30)14-29(21)35-25;;;/h13-16H,7-12H2,1-6H3,(H4,35,36,37,38,39,40,41,42);2*1H;/q;;;+4/p-4/b25-13-,26-13-,27-14-,28-15-,29-14-,30-15-,31-16-,32-16-;;;
IUPAC Name
tin(4+) ion 5,9-bis(2-carboxyethyl)-14,19-diethyl-4,10,15,20-tetramethyl-21,22,23,24-tetraazapentacyclo[16.2.1.1^{3,6}.1^{8,11}.1^{13,16}]tetracosa-1(20),2,4,6(24),7,9,11,13(22),14,16,18-undecaene-21,23-diide dichloride
SMILES
[Cl-].[Cl-].[Sn+4].CCC1=C2[N-]C(\C=C3/N=C(/C=C4\[N-]\C(=C/C5=N/C(=C\2)/C(C)=C5CC)C(C)=C4CCC(O)=O)C(CCC(O)=O)=C3C)=C1C

Pharmacology

Indication

Investigated for use/treatment in liver disease, metabolic disease, and pediatric indications.

Structured Indications
Not Available
Pharmacodynamics

Stannsoporfin is a chemical compound being investigated for use as a medicament in the treatment of infant jaundice. Stannsoporfin is also known to inhibit heme metabolism in mammals, to control the rate of tryptophan metabolism in mammals, and to increase the rate at which heme is excreted by mammals.

Mechanism of action

Kernicterus is attributed to high levels of bilirubin, a by-product of heme metabolism. Bilirubin is a bile pigment, which is normally eliminated from the body after conversion into a water-soluble form by the liver. Stannsoporfin's mechanism of action specifically inhibits the enzyme that blocks the conversion of heme into bilirubin.

TargetActionsOrganism
UHeme oxygenase 1Not AvailableHuman
UHeme oxygenase 2Not AvailableHuman
Absorption

Not absorbed orally

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life

3.8 hours following i.v. administration of 1 mumole per kg body weight

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. Galbraith RA, Kappas A: Pharmacokinetics of tin-mesoporphyrin in man and the effects of tin-chelated porphyrins on hyperexcretion of heme pathway precursors in patients with acute inducible porphyria. Hepatology. 1989 Jun;9(6):882-8. [PubMed:2714739]
External Links
PubChem Compound
15978579
PubChem Substance
347827700
ChemSpider
7869402

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedNot AvailableJaundice / Neonatal Hyperbilirubinemia1
2CompletedTreatmentHyperbilirubinemia1
2CompletedTreatmentJaundice, Neonatal / Neonatal Hyperbilirubinemia1
2TerminatedTreatmentNeonatal Hyperbilirubinemia1
3CompletedPreventionNutritional and Metabolic Diseases1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0106 mg/mLALOGPS
logP5.4ALOGPS
logP7.05ChemAxon
logS-4.8ALOGPS
pKa (Strongest Acidic)3.73ChemAxon
pKa (Strongest Basic)5.04ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count8ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area126.16 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity164.94 m3·mol-1ChemAxon
Polarizability66.7 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Classification
Not classified

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Signal transducer activity
Specific Function
Heme oxygenase cleaves the heme ring at the alpha methene bridge to form biliverdin. Biliverdin is subsequently converted to bilirubin by biliverdin reductase. Under physiological conditions, the a...
Gene Name
HMOX1
Uniprot ID
P09601
Uniprot Name
Heme oxygenase 1
Molecular Weight
32818.345 Da
References
  1. Drummond GS, Kappas A: Chemoprevention of severe neonatal hyperbilirubinemia. Semin Perinatol. 2004 Oct;28(5):365-8. [PubMed:15686268]
  2. Cannon JB, Martin C, Drummond GS, Kappas A: Targeted delivery of a heme oxygenase inhibitor with a lyophilized liposomal tin mesoporphyrin formulation. Pharm Res. 1993 May;10(5):715-21. [PubMed:8321837]
  3. Boni RE, Huch Boni RA, Galbraith RA, Drummond GS, Kappas A: Tin-mesoporphyrin inhibits heme oxygenase activity and heme-iron absorption in the intestine. Pharmacology. 1993 Nov;47(5):318-29. [PubMed:8265722]
  4. Wagner KR, Hua Y, de Courten-Myers GM, Broderick JP, Nishimura RN, Lu SY, Dwyer BE: Tin-mesoporphyrin, a potent heme oxygenase inhibitor, for treatment of intracerebral hemorrhage: in vivo and in vitro studies. Cell Mol Biol (Noisy-le-grand). 2000 May;46(3):597-608. [PubMed:10872746]
  5. Nalos M, Vassilev D, Pittner A, Asfar P, Bruckner UB, Schneider EM, Georgieff M, Radermacher P, Froeba G: Tin-mesoporphyrin for inhibition of heme oxygenase during long-term hyperdynamic porcine endotoxemia. Shock. 2003 Jun;19(6):526-32. [PubMed:12785007]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Metal ion binding
Specific Function
Heme oxygenase cleaves the heme ring at the alpha methene bridge to form biliverdin. Biliverdin is subsequently converted to bilirubin by biliverdin reductase. Under physiological conditions, the a...
Gene Name
HMOX2
Uniprot ID
P30519
Uniprot Name
Heme oxygenase 2
Molecular Weight
36032.615 Da
References
  1. Drummond GS, Kappas A: Chemoprevention of severe neonatal hyperbilirubinemia. Semin Perinatol. 2004 Oct;28(5):365-8. [PubMed:15686268]
  2. Cannon JB, Martin C, Drummond GS, Kappas A: Targeted delivery of a heme oxygenase inhibitor with a lyophilized liposomal tin mesoporphyrin formulation. Pharm Res. 1993 May;10(5):715-21. [PubMed:8321837]
  3. Boni RE, Huch Boni RA, Galbraith RA, Drummond GS, Kappas A: Tin-mesoporphyrin inhibits heme oxygenase activity and heme-iron absorption in the intestine. Pharmacology. 1993 Nov;47(5):318-29. [PubMed:8265722]
  4. Wagner KR, Hua Y, de Courten-Myers GM, Broderick JP, Nishimura RN, Lu SY, Dwyer BE: Tin-mesoporphyrin, a potent heme oxygenase inhibitor, for treatment of intracerebral hemorrhage: in vivo and in vitro studies. Cell Mol Biol (Noisy-le-grand). 2000 May;46(3):597-608. [PubMed:10872746]
  5. Nalos M, Vassilev D, Pittner A, Asfar P, Bruckner UB, Schneider EM, Georgieff M, Radermacher P, Froeba G: Tin-mesoporphyrin for inhibition of heme oxygenase during long-term hyperdynamic porcine endotoxemia. Shock. 2003 Jun;19(6):526-32. [PubMed:12785007]

Drug created on October 21, 2007 16:23 / Updated on December 01, 2017 15:34