Details
Stereochemistry | ACHIRAL |
Molecular Formula | C34H32N4O4.Fe.HO |
Molecular Weight | 633.495 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
[OH-].[Fe+3].CC1=C(CCC(O)=O)C2=CC3=NC(=CC4=C(C)C(C=C)=C([N-]4)C=C5N=C(C=C1[N-]2)C(C=C)=C5C)C(C)=C3CCC(O)=O
InChI
InChIKey=BMUDPLZKKRQECS-HXFTUNQESA-K
InChI=1S/C34H34N4O4.Fe.H2O/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;;/h7-8,13-16H,1-2,9-12H2,3-6H3,(H4,35,36,37,38,39,40,41,42);;1H2/q;+3;/p-3/b25-13-,26-13-,27-14-,28-15-,29-14-,30-15-,31-16-,32-16-;;
Molecular Formula | Fe |
Molecular Weight | 55.845 |
Charge | 3 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
Molecular Formula | C34H32N4O4 |
Molecular Weight | 560.6423 |
Charge | -2 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
Molecular Formula | HO |
Molecular Weight | 17.0073 |
Charge | -1 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
DescriptionCurator's Comment: Description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/17766326
Curator's Comment: Description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/17766326
Protoporphyrin IX, an effective photosensitizer. 5-ALA is a prodrug that can be converted by the heme biosynthetic pathway into protoporphyrin IX. Protoporphyrin (cobalt protoporphyrin IX ) was known to be a substrate for heme oxygenase (HO), now identified as a potent HO-1 inducer. Cobalt protoporphyrin IX has been shown to downregulate various cytochrome P450 isoforms, and various mechanisms of action have been attributed to its ability to induced HO- 1. It has also been used to promote endogenous carbon dioxide (CO) generation and protect against myocardial infarction in vivo. Cobalt protoporphyrin also participated in regulating the inflammatory response in CNS which mainly suppressed inflammatory component. It has been demonstrated that CoPP reduced LPS/Interleukin 13 (IL-13)-induced microglial death. It has being shown, that cobalt protoporphyrin upregulates Cyclooxygenase-2 expression through a heme oxygenase-independent mechanism.
CNS Activity
Sources: https://www.ncbi.nlm.nih.gov/pubmed/24952361
Curator's Comment: hemin improves barrier function and neurological outcome in experimental models of traumatic and ischemic CNS injury
Originator
Sources: http://adisinsight.springer.com/drugs/800002495http://www.nejm.org/doi/full/10.1056/NEJM194501042320103#t=article
Curator's Comment: Protoporphyrin was first found to be an iron-free derivative of hemoglobin by Kämmerer in 1923
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: Ultrasonically-induced cell damage Sources: https://www.ncbi.nlm.nih.gov/pubmed/20189622 |
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Target ID: CHEMBL243 Sources: https://www.ncbi.nlm.nih.gov/pubmed/1527792 |
200.0 µM [IC50] | ||
Target ID: CHEMBL2823 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26877238 |
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Target ID: CHEMBL2977 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26255181 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Prolmon Approved UseTreatment of liver disorders |
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Primary | Panhematin Approved UsePANHEMATIN (hemin for injection) is indicated for the amelioration of recurrent attacks of acute intermittent porphyria temporally related to the menstrual cycle in susceptible women. Manifestations such as pain, hypertension, tachycardia, abnormal mental status and mild to progressive neurologic signs may be controlled in selected patients with this disorder. Similar findings have been reported in other patients with acute intermittent porphyria, porphyria variegata and hereditary coproporphyria. PANHEMATIN is not indicated in porphyria cutanea tarda. |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
742 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9372622/ |
40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered: |
PROTOPORPHYRIN plasma | Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
9.6 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9372622/ |
40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered: |
PROTOPORPHYRIN plasma | Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9372622/ |
40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered: |
PROTOPORPHYRIN plasma | Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN |
PubMed
Title | Date | PubMed |
---|---|---|
[Thin layer chromatographic separation of porphyrins, hemin and lipids on Silica Gel H plates for the determination of the erythrocyte porphyrins as their methyl esters]. | 1968 Jun 4 |
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Iron protoporphyrin IX (hemin) but not tin or zinc protoporphyrin IX can stimulate gene expression in K562 cells from enhancer elements containing binding sites for NF-E2. | 1994 Aug 15 |
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Effects of combinations of stem cell factor and hemin on erythropoiesis after azidothymidine treatment of immunosuppressed mice. | 1996 Aug |
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Expression of heme oxygenase isozyme mRNAs in the human brain and induction of heme oxygenase-1 by nitric oxide donors. | 1996 Aug |
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Development of refractoriness of induced human heme oxygenase-1 gene expression to reinduction by UVA irradiation and hemin. | 1997 Oct |
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Effect of lindane and heptachlor on delta-aminolaevulinate synthase and its regulation. | 1998 Nov |
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Involvement of the tyrosine phosphorylation pathway in induction of human heme oxygenase-1 by hemin, sodium arsenite, and cadmium chloride. | 1998 Sep |
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Comparative effect of ALA derivatives on protoporphyrin IX production in human and rat skin organ cultures. | 1999 Jul |
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Reactive carbonyl formation by oxidative and non-oxidative pathways. | 2001 Aug 1 |
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The influence of UV exposure on 5-aminolevulinic acid-induced protoporphyrin IX production in skin. | 2001 Dec |
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Human NADPH-P450 oxidoreductase modulates the level of cytochrome P450 CYP2D6 holoprotein via haem oxygenase-dependent and -independent pathways. | 2001 Jun 1 |
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Differential induction of heme oxygenase-1 in macrophages and hepatocytes during acetaminophen-induced hepatotoxicity in the rat: effects of hemin and biliverdin. | 2002 Jun 1 |
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Selective regulation of blood pressure by heme oxygenase-1 in hypertension. | 2002 Sep |
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Relationships and distinctions in iron-regulatory networks responding to interrelated signals. | 2003 May 1 |
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Inhibition of lipopolysaccharide-induced nitric oxide production by flavonoids in RAW264.7 macrophages involves heme oxygenase-1. | 2003 Nov 1 |
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Overexpression of transglutaminase 2 accelerates the erythroid differentiation of human chronic myelogenous leukemia K562 cell line through PI3K/Akt signaling pathway. | 2004 Nov 19 |
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Anti-inflammatory effect of heme oxygenase 1: glycosylation and nitric oxide inhibition in macrophages. | 2005 Feb |
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Distinct protective mechanisms of HO-1 and HO-2 against hydroperoxide-induced cytotoxicity. | 2005 Jan 1 |
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Nitric oxide-mediated nitrosation of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline potentiated by hemin and myeloperoxidase. | 2005 Jun |
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Alteration at translational but not transcriptional level of transferrin receptor expression following manganese exposure at the blood-CSF barrier in vitro. | 2005 Jun 1 |
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Novel lipid mediator aspirin-triggered lipoxin A4 induces heme oxygenase-1 in endothelial cells. | 2005 Sep |
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Piceatannol upregulates endothelial heme oxygenase-1 expression via novel protein kinase C and tyrosine kinase pathways. | 2006 Feb |
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Heme oxygenase 2 is neuroprotective against intracerebral hemorrhage. | 2006 Jun |
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Heme oxygenase-1 protects tumor cells against photodynamic therapy-mediated cytotoxicity. | 2006 Jun 8 |
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JWA, a novel signaling molecule, involved in the induction of differentiation of human myeloid leukemia cells. | 2006 Mar 10 |
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Curcumin reduces cold storage-induced damage in human cardiac myoblasts. | 2007 Apr 30 |
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Identification of heat shock protein 32 (Hsp32) as a novel survival factor and therapeutic target in neoplastic mast cells. | 2007 Jul 15 |
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BACH1 is a specific repressor of HMOX1 that is inactivated by arsenite. | 2008 Aug 15 |
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Carbon monoxide donors or heme oxygenase-1 (HO-1) overexpression blocks interleukin-18-mediated NF-kappaB-PTEN-dependent human cardiac endothelial cell death. | 2008 Feb 1 |
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Heme oxygenase-1 mediates the anti-inflammatory effect of Curcumin within LPS-stimulated human monocytes. | 2008 Jun |
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Protective effects of bilirubin against cyclophosphamide induced hemorrhagic cystitis in rats. | 2008 Mar |
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Interaction among heme oxygenase, nuclear factor-kappaB, and transcription activating factors in cardiac hypertrophy in hypertension. | 2008 Nov |
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Induction of heme oxygenase-1 with hemin attenuates hippocampal injury in rats after acute carbon monoxide poisoning. | 2009 Aug 3 |
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Protective effect of hemin against cadmium-induced testicular damage in rats. | 2009 Mar 29 |
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Upregulating the heme oxygenase system suppresses left ventricular hypertrophy in adult spontaneously hypertensive rats for 3 months. | 2009 Sep |
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The heme oxygenase system attenuates pancreatic lesions and improves insulin sensitivity and glucose metabolism in deoxycorticosterone acetate hypertension. | 2010 Jan |
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Astaxanthin protects against MPP(+)-induced oxidative stress in PC12 cells via the HO-1/NOX2 axis. | 2012 Dec 29 |
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Heme and heme biosynthesis intermediates induce heme oxygenase-1 and cytochrome P450 2A5, enzymes with putative sequential roles in heme and bilirubin metabolism: different requirement for transcription factor nuclear factor erythroid- derived 2-like 2. | 2012 Nov |
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A functional link between heme oxygenase-1 and tristetraprolin in the anti-inflammatory effects of nicotine. | 2013 Dec |
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The role of catechol-O-methyltransferase in catechol-enhanced erythroid differentiation of K562 cells. | 2013 Dec 15 |
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Heme oxygenase-1 alleviates vascular complications associated with metabolic syndrome: Effect on endothelial dependent relaxation and NO production. | 2014 Nov 5 |
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Transcriptional upregulation centra of HO-1 by EGB via the MAPKs/Nrf2 pathway in mouse C2C12 myoblasts. | 2015 Mar |
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Constitutive active/androstane receptor, peroxisome proliferator-activated receptor α, and cytotoxicity are involved in oxadiazon-induced liver tumor development in mice. | 2016 Feb |
Sample Use Guides
An intravenous infusion of PANHEMATIN containing a dose of 1 to 4 mg/kg/day of hematin should be given over a period of 10 to 15 minutes for 3 to 14 days based on the clinical signs. In more severe cases this dose may be repeated no earlier than every 12 hours. No more than 6 mg/kg of hematin should be given in any 24 hour period.
Route of Administration:
Intravenous
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/3559294
Hemin stimulates erythropoiesis and hemoglobin synthesis in vitro. It was cultured erythroid progenitor cells from normal individuals, patients with sickle cell anemia, and a patient with acute variegate porphyria who received intravenous hemin treatment, with 0-800 microM hemin added in vitro. Fifty to 200 microM hemin consistently stimulated colony growth from normal donors 2- to 8-fold, while concentrations of up to 400 microM were stimulatory in cultures from donors with sickle cell anemia. In vivo hemin decreased the number of blood BFU-e in the patient with porphyria, but did not abrogate the in vitro stimulatory effect of hemin. Hemin concentrations which increased colony numbers increased gamma globin synthesis in some studies and decreased it in others. Hemin thus has clearcut erythroid growth-potentiating activity, although a consistent effect on globin chain regulation is not apparent.
Substance Class |
Chemical
Created
by
admin
on
Edited
Fri Dec 16 15:52:06 UTC 2022
by
admin
on
Fri Dec 16 15:52:06 UTC 2022
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Record UNII |
0WP180G15G
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Record Status |
Validated (UNII)
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Record Version |
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WHO-ATC |
B06AB01
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WHO-VATC |
QB06AB01
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15489-90-4
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239-518-9
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4565
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CHEMBL3707238
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SUB12511MIG
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M5940
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PRIMARY | Merck Index | ||
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0WP180G15G
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DB13387
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36161
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