HEMATIN

US Approved Rx (1983)

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

Structure Search

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-;;

HIDE SMILES / InChI

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

Description
Sources: http://www.rxlist.com/panhematin-drug.htmhttps://www.ncbi.nlm.nih.gov/pubmed/26255181
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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Target ID: Ultrasonically-induced cell damage Sources: https://www.ncbi.nlm.nih.gov/pubmed/20189622	Activator 1404
Human immunodeficiency virus type 1 protease 35 Target ID: CHEMBL243 Sources: https://www.ncbi.nlm.nih.gov/pubmed/1527792	Inhibitor 8146	200.0 µM [IC50]
Heme oxygenase 1 15 Target ID: CHEMBL2823 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26877238	Activator 1404
Cyclooxygenase-2 191 Target ID: CHEMBL2977 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26255181	Activator 1404

Conditions

Condition	Modality	Highest Phase	Product
Diabetic neuropathy 23 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26730587	Primary	Basic research	Unknown Approved Use Unknown
Parkinson's disease 223 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26385576	Primary	Basic research	Unknown Approved Use Unknown
Type 1 diabetes mellitus 17 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26252059	Primary	Basic research	Unknown Approved Use Unknown
Liver diseases 14 Sources: http://211.103.242.133:8080/ziyuan/CDDPdf/med/base/%E8%8D%AF%E5%93%81hu/%E6%B6%88%E5%8C%96%E7%B3%BB%E7%BB%9F%E8%8D%AF%E7%89%A9/1013.pdf http://jglobal.jst.go.jp/public/20090422/200902091490310298	Primary	Approved 8307	Prolmon Approved Use Treatment of liver disorders
Acute intermittent porphyria 7 Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d84808a8-d039-6293-6e0d-782327f0a5c0	Primary	Approved 8307	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.

C_max

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

T_1/2

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

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	BCRP 545

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
BCRP 545	substrate 3264 Sources: https://www.tandfonline.com/doi/pdf/10.4161/cbt.4.2.1440\|https://pubmed.ncbi.nlm.nih.gov/28118809/	major

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:15430	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:15430
MolPort	MolPort-003-665-944	https://www.molport.com/shop/molecule-link/MolPort-003-665-944
eMolecules	18593072	https://www.emolecules.com/cgi-bin/more?vid=18593072
eMolecules	531182	https://www.emolecules.com/cgi-bin/more?vid=531182

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	4297976
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	8049443
Effects of combinations of stem cell factor and hemin on erythropoiesis after azidothymidine treatment of immunosuppressed mice.	1996 Aug	8856089
Expression of heme oxygenase isozyme mRNAs in the human brain and induction of heme oxygenase-1 by nitric oxide donors.	1996 Aug	8764571
Development of refractoriness of induced human heme oxygenase-1 gene expression to reinduction by UVA irradiation and hemin.	1997 Oct	9337616
Effect of lindane and heptachlor on delta-aminolaevulinate synthase and its regulation.	1998 Nov	9879810
Involvement of the tyrosine phosphorylation pathway in induction of human heme oxygenase-1 by hemin, sodium arsenite, and cadmium chloride.	1998 Sep	9722676
Comparative effect of ALA derivatives on protoporphyrin IX production in human and rat skin organ cultures.	1999 Jul	10408393
Reactive carbonyl formation by oxidative and non-oxidative pathways.	2001 Aug 1	11487471
The influence of UV exposure on 5-aminolevulinic acid-induced protoporphyrin IX production in skin.	2001 Dec	11783939
Human NADPH-P450 oxidoreductase modulates the level of cytochrome P450 CYP2D6 holoprotein via haem oxygenase-dependent and -independent pathways.	2001 Jun 1	11368792
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	12051994
Selective regulation of blood pressure by heme oxygenase-1 in hypertension.	2002 Sep	12215473
Relationships and distinctions in iron-regulatory networks responding to interrelated signals.	2003 May 1	12393473
Inhibition of lipopolysaccharide-induced nitric oxide production by flavonoids in RAW264.7 macrophages involves heme oxygenase-1.	2003 Nov 1	14563492
Overexpression of transglutaminase 2 accelerates the erythroid differentiation of human chronic myelogenous leukemia K562 cell line through PI3K/Akt signaling pathway.	2004 Nov 19	15556610
Anti-inflammatory effect of heme oxygenase 1: glycosylation and nitric oxide inhibition in macrophages.	2005 Feb	15316927
Distinct protective mechanisms of HO-1 and HO-2 against hydroperoxide-induced cytotoxicity.	2005 Jan 1	15589375
Nitric oxide-mediated nitrosation of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline potentiated by hemin and myeloperoxidase.	2005 Jun	15962939
Alteration at translational but not transcriptional level of transferrin receptor expression following manganese exposure at the blood-CSF barrier in vitro.	2005 Jun 1	15893546
Novel lipid mediator aspirin-triggered lipoxin A4 induces heme oxygenase-1 in endothelial cells.	2005 Sep	15901601
Piceatannol upregulates endothelial heme oxygenase-1 expression via novel protein kinase C and tyrosine kinase pathways.	2006 Feb	16243536
Heme oxygenase 2 is neuroprotective against intracerebral hemorrhage.	2006 Jun	16459095
Heme oxygenase-1 protects tumor cells against photodynamic therapy-mediated cytotoxicity.	2006 Jun 8	16462769
JWA, a novel signaling molecule, involved in the induction of differentiation of human myeloid leukemia cells.	2006 Mar 10	16430862
Curcumin reduces cold storage-induced damage in human cardiac myoblasts.	2007 Apr 30	17464175
Identification of heat shock protein 32 (Hsp32) as a novel survival factor and therapeutic target in neoplastic mast cells.	2007 Jul 15	17420286
BACH1 is a specific repressor of HMOX1 that is inactivated by arsenite.	2008 Aug 15	18550526
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	18215737
Heme oxygenase-1 mediates the anti-inflammatory effect of Curcumin within LPS-stimulated human monocytes.	2008 Jun	18357586
Protective effects of bilirubin against cyclophosphamide induced hemorrhagic cystitis in rats.	2008 Mar	18206168
Interaction among heme oxygenase, nuclear factor-kappaB, and transcription activating factors in cardiac hypertrophy in hypertension.	2008 Nov	18824663
Induction of heme oxygenase-1 with hemin attenuates hippocampal injury in rats after acute carbon monoxide poisoning.	2009 Aug 3	19520142
Protective effect of hemin against cadmium-induced testicular damage in rats.	2009 Mar 29	19150641
Upregulating the heme oxygenase system suppresses left ventricular hypertrophy in adult spontaneously hypertensive rats for 3 months.	2009 Sep	19700139
The heme oxygenase system attenuates pancreatic lesions and improves insulin sensitivity and glucose metabolism in deoxycorticosterone acetate hypertension.	2010 Jan	19864334
Astaxanthin protects against MPP(+)-induced oxidative stress in PC12 cells via the HO-1/NOX2 axis.	2012 Dec 29	23272707
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	22859313
A functional link between heme oxygenase-1 and tristetraprolin in the anti-inflammatory effects of nicotine.	2013 Dec	24095726
The role of catechol-O-methyltransferase in catechol-enhanced erythroid differentiation of K562 cells.	2013 Dec 15	24141029
Heme oxygenase-1 alleviates vascular complications associated with metabolic syndrome: Effect on endothelial dependent relaxation and NO production.	2014 Nov 5	25268984
Transcriptional upregulation centra of HO-1 by EGB via the MAPKs/Nrf2 pathway in mouse C2C12 myoblasts.	2015 Mar	25449124
Constitutive active/androstane receptor, peroxisome proliferator-activated receptor α, and cytotoxicity are involved in oxadiazon-induced liver tumor development in mice.	2016 Feb	26710982

Patents

Sample Use Guides

In Vivo Use Guide

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 15:52:06 UTC 2022` Edited by `admin` on `Fri Dec 16 15:52:06 UTC 2022`
Record UNII	0WP180G15G
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

HEMATIN

Official Name

English

PHENODIN

Common Name

English

FERRATE(2-), (7,12-DIETHENYL-3,8,13,17-TETRAMETHYL-21H,23H-PORPHINE-2,18-DIPROPANOATO(4-)-.KAPPA.N21,.KAPPA.N22,.KAPPA.N23,.KAPPA.N24)HYDROXY-, HYDROGEN (1:2), (SP-5-13)-

Systematic Name

English

FERRIHEME HYDROXIDE

Common Name

English

FERRIPROTOPORPHYRIN BASIC

Common Name

English

HEMATIN [INCI]

Common Name

English

Hematin [WHO-DD]

Common Name

English

HEMATIN [MI]

Common Name

English

FERRIPORPHYRIN HYDROXIDE

Common Name

English

HYDROXYHEMIN

Common Name

English

Classification Tree Code System Code

WHO-ATC

B06AB01