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Details

Stereochemistry ACHIRAL
Molecular Formula C34H32N4O4.Cl.Fe
Molecular Weight 651.94
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of HEMIN

SMILES

[Cl-].[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)=C5C=C)C(C)=C3CCC(O)=O

InChI

InChIKey=BTIJJDXEELBZFS-HXFTUNQESA-K
InChI=1S/C34H34N4O4.ClH.Fe/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);1H;/q;;+3/p-3/b25-13-,26-13-,27-14-,28-15-,29-14-,30-15-,31-16-,32-16-;;

HIDE SMILES / InChI

Molecular Formula C34H30N4O4
Molecular Weight 558.6264
Charge -2
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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 ClH
Molecular Weight 36.461
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
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

Curator's Comment: hemin improves barrier function and neurological outcome in experimental models of traumatic and ischemic CNS injury

Originator

Curator's Comment: Protoporphyrin was first found to be an iron-free derivative of hemoglobin by Kämmerer in 1923

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: Ultrasonically-induced cell damage
200.0 µM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Prolmon

Approved Use

Treatment of liver disorders
Primary
Panhematin

Approved Use

PANHEMATIN (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

Cmax

ValueDoseCo-administeredAnalytePopulation
742 ng/mL
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

AUC

ValueDoseCo-administeredAnalytePopulation
9.6 μg × h/mL
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

T1/2

ValueDoseCo-administeredAnalytePopulation
4 h
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
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer

Drug as victim

Drug as victim

PubMed

PubMed

TitleDatePubMed
The selective enhancing influence of hemin and products of human erythrocytes on colony formation by human multipotential (CFUGEMM) and erythroid (BFUE) progenitor cells in vitro.
1983 Sep
[Protoporphyrin IX level in erythrocytes of persons with alcoholic liver cirrhosis].
1985 Jul 15
Simultaneous quantification of erythrocyte zinc protoporphyrin and protoporphyrin IX by liquid chromatography.
1986 Dec
Prevention of anthracycline-induced cytotoxicity in hemopoietic cells by hemin.
1986 Jul
Evidence suggesting that the two forms of heme oxygenase are products of different genes.
1988 Mar 5
Effects of hemin on erythropoiesis.
1989
Protoporphyrin IX photosensitization of corneal endothelium.
1989 Oct
The synergistic effect of hemin and transforming growth factor-beta on hemoglobin accumulation in HEL erythroleukemia cells.
1991
Long-term intercalation of residual hemin in erythrocyte membranes distorts the cell.
1991 Feb 11
Development of refractoriness of induced human heme oxygenase-1 gene expression to reinduction by UVA irradiation and hemin.
1997 Oct
Pharmacokinetics of 5-aminolevulinic acid-induced protoporphyrin IX in skin and blood.
1997 Oct
Involvement of the tyrosine phosphorylation pathway in induction of human heme oxygenase-1 by hemin, sodium arsenite, and cadmium chloride.
1998 Sep
Comparative effect of ALA derivatives on protoporphyrin IX production in human and rat skin organ cultures.
1999 Jul
Suppression of heme oxygenase-1 mRNA expression by interferon-gamma in human glioblastoma cells.
1999 Jun
A screening assay for antiviral compounds targeted to the HIV-1 gp41 core structure using a conformation-specific monoclonal antibody.
1999 Jun
The heme synthesis and degradation pathways: role in oxidant sensitivity. Heme oxygenase has both pro- and antioxidant properties.
2000 Jan 15
Accumulation of protoporphyrin-IX (PpIX) in leukemic cell lines following induction by 5-aminolevulinic acid (ALA).
2000 Jul
A key role for the mitochondrial benzodiazepine receptor in cellular photosensitisation with delta-aminolaevulinic acid.
2000 Oct 13
[Determination of blood glucose by chemiluminescent flow-injection analysis with immobilized glucoxidase column].
2000 Sep
The influence of UV exposure on 5-aminolevulinic acid-induced protoporphyrin IX production in skin.
2001 Dec
Human NADPH-P450 oxidoreductase modulates the level of cytochrome P450 CYP2D6 holoprotein via haem oxygenase-dependent and -independent pathways.
2001 Jun 1
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
Selective regulation of blood pressure by heme oxygenase-1 in hypertension.
2002 Sep
Crystal structural analysis of human serum albumin complexed with hemin and fatty acid.
2003 Jul 7
Inhibition of lipopolysaccharide-induced nitric oxide production by flavonoids in RAW264.7 macrophages involves heme oxygenase-1.
2003 Nov 1
The role of endogenous heme synthesis and degradation domain cysteines in cellular iron-dependent degradation of IRP2.
2003 Sep-Oct
Metalloporphyrins inactivate caspase-3 and -8.
2005 Aug
Correlation between macroscopic fluorescence and protoporphyrin IX content in psoriasis and actinic keratosis following application of aminolevulinic acid.
2005 Oct
Novel lipid mediator aspirin-triggered lipoxin A4 induces heme oxygenase-1 in endothelial cells.
2005 Sep
Iron regulation and the cell cycle: identification of an iron-responsive element in the 3'-untranslated region of human cell division cycle 14A mRNA by a refined microarray-based screening strategy.
2006 Aug 11
Piceatannol upregulates endothelial heme oxygenase-1 expression via novel protein kinase C and tyrosine kinase pathways.
2006 Feb
Heme oxygenase-1 protects tumor cells against photodynamic therapy-mediated cytotoxicity.
2006 Jun 8
Accumulation of protoporphyrin-IX in rat Leydig cells following induction by 5-aminolevulinic acid and tramadol.
2007 Dec
Identification of heat shock protein 32 (Hsp32) as a novel survival factor and therapeutic target in neoplastic mast cells.
2007 Jul 15
JunB and JunD regulate human heme oxygenase-1 gene expression in renal epithelial cells.
2007 Mar 2
BACH1 is a specific repressor of HMOX1 that is inactivated by arsenite.
2008 Aug 15
Catalytic inactive heme oxygenase-1 protein regulates its own expression in oxidative stress.
2008 Mar 1
Cystathionine beta-synthase as a carbon monoxide-sensitive regulator of bile excretion.
2009 Jan
Sulfasalazine induces haem oxygenase-1 via ROS-dependent Nrf2 signalling, leading to control of neointimal hyperplasia.
2009 Jun 1
Arsenite down-regulates cytochrome P450 1A1 at the transcriptional and posttranslational levels in human HepG2 cells.
2010 May 15
DMF inhibits PDGF-BB induced airway smooth muscle cell proliferation through induction of heme-oxygenase-1.
2010 Oct 20
Transcriptional and posttranslational mechanisms modulating the expression of the cytochrome P450 1A1 gene by lead in HepG2 cells: a role of heme oxygenase.
2012 Jan 27
Inhibition of heme oxygenase-1 partially reverses the arsenite-mediated decrease of CYP1A1, CYP1A2, CYP3A23, and CYP3A2 catalytic activity in isolated rat hepatocytes.
2012 Mar
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
Small molecule activators of the Nrf2-HO-1 antioxidant axis modulate heme metabolism and inflammation in BV2 microglia cells.
2013 Oct
Changes in DNA methylation of erythroid-specific genes in K562 cells exposed to phenol and hydroquinone.
2013 Oct 4
Carbon Monoxide (CO) Released from Tricarbonyldichlororuthenium (II) Dimer (CORM-2) in Gastroprotection against Experimental Ethanol-Induced Gastric Damage.
2015
Neuroprotective role of prostaglandin PGE2 EP2 receptor in hemin-mediated toxicity.
2015 Jan
Transcriptional upregulation centra of HO-1 by EGB via the MAPKs/Nrf2 pathway in mouse C2C12 myoblasts.
2015 Mar
Key role of phosphodiesterase 4A (PDE4A) in autophagy triggered by yessotoxin.
2015 Mar 2
Patents

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
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 Fri Dec 16 20:51:26 UTC 2022
Edited
by admin
on Fri Dec 16 20:51:26 UTC 2022
Record UNII
743LRP9S7N
Record Status Validated (UNII)
Record Version
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Name Type Language
HEMIN
MI   VANDF   WHO-DD  
Common Name English
Hemin [WHO-DD]
Common Name English
HEMIN [MI]
Common Name English
FERRIPROTOPORPHYRIN CHLORIDE
Common Name English
NSC-122707
Code English
HEMIN [JAN]
Common Name English
FERRATE(2-), CHLORO(7,12-DIETHENYL-3,8,13,17-TETRAMETHYL-21H,23H-PORPHINE-2,18-DIPROPANOATO(4-)-N21,N22,N23,N24)-, DIHYDROGEN
Common Name English
HEMIN [VANDF]
Common Name English
CHLOROHEMIN
Common Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 683
Created by admin on Fri Dec 16 20:51:26 UTC 2022 , Edited by admin on Fri Dec 16 20:51:26 UTC 2022
FDA ORPHAN DRUG 77393
Created by admin on Fri Dec 16 20:51:26 UTC 2022 , Edited by admin on Fri Dec 16 20:51:26 UTC 2022
Code System Code Type Description
DAILYMED
743LRP9S7N
Created by admin on Fri Dec 16 20:51:26 UTC 2022 , Edited by admin on Fri Dec 16 20:51:26 UTC 2022
PRIMARY
DRUG CENTRAL
5117
Created by admin on Fri Dec 16 20:51:26 UTC 2022 , Edited by admin on Fri Dec 16 20:51:26 UTC 2022
PRIMARY
DRUG BANK
DB03404
Created by admin on Fri Dec 16 20:51:26 UTC 2022 , Edited by admin on Fri Dec 16 20:51:26 UTC 2022
PRIMARY
ECHA (EC/EINECS)
240-140-1
Created by admin on Fri Dec 16 20:51:26 UTC 2022 , Edited by admin on Fri Dec 16 20:51:26 UTC 2022
PRIMARY
CAS
16009-13-5
Created by admin on Fri Dec 16 20:51:26 UTC 2022 , Edited by admin on Fri Dec 16 20:51:26 UTC 2022
PRIMARY
MESH
D006427
Created by admin on Fri Dec 16 20:51:26 UTC 2022 , Edited by admin on Fri Dec 16 20:51:26 UTC 2022
PRIMARY
EVMPD
SUB14075MIG
Created by admin on Fri Dec 16 20:51:26 UTC 2022 , Edited by admin on Fri Dec 16 20:51:26 UTC 2022
PRIMARY
FDA UNII
743LRP9S7N
Created by admin on Fri Dec 16 20:51:26 UTC 2022 , Edited by admin on Fri Dec 16 20:51:26 UTC 2022
PRIMARY
WIKIPEDIA
HEMIN
Created by admin on Fri Dec 16 20:51:26 UTC 2022 , Edited by admin on Fri Dec 16 20:51:26 UTC 2022
PRIMARY
MERCK INDEX
M5949
Created by admin on Fri Dec 16 20:51:26 UTC 2022 , Edited by admin on Fri Dec 16 20:51:26 UTC 2022
PRIMARY Merck Index
RXCUI
5175
Created by admin on Fri Dec 16 20:51:26 UTC 2022 , Edited by admin on Fri Dec 16 20:51:26 UTC 2022
PRIMARY RxNorm
CHEBI
50385
Created by admin on Fri Dec 16 20:51:26 UTC 2022 , Edited by admin on Fri Dec 16 20:51:26 UTC 2022
PRIMARY
NSC
122707
Created by admin on Fri Dec 16 20:51:26 UTC 2022 , Edited by admin on Fri Dec 16 20:51:26 UTC 2022
PRIMARY
EPA CompTox
DTXSID9037662
Created by admin on Fri Dec 16 20:51:26 UTC 2022 , Edited by admin on Fri Dec 16 20:51:26 UTC 2022
PRIMARY
Related Record Type Details
PARENT -> SALT/SOLVATE
Related Record Type Details
ACTIVE MOIETY