Details of the Drug

General Information of Drug (ID: DMGC287)

Drug Name

Heme

Synonyms

heme; protoheme; Haem; ferroprotoporphyrin; UNII-42VZT0U6YR; Iron protoporphyrin ix; Protohaem; Ferroheme; Reduced hematin; Ferrous protoheme; Iron protoporphyrin; Ferrous protoheme IX; Ferroprotoporphyrin IX; 14875-96-8; 42VZT0U6YR; Iron(II) protoporphyrin IX; Protoheme IX (VAN); Ferroheme (VAN); Heme (VAN); 85758-EP2305825A1; 85758-EP2305243A1; 85758-EP2270505A1; 85758-EP2270016A1; 3-[18-(2-carboxyethyl)-7,12-bis(ethenyl)-3,8,13,17-tetramethylporphyrin-21,23-diid-2-yl]propanoic acid; iron(2+); NSC 16669; NSC 267100; AC1L9FPJ; Hemin

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]
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Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski):
1

Molecular Weight

616.5

Logarithm of the Partition Coefficient

Not Available

Rotatable Bond Count

Hydrogen Bond Donor Count

Hydrogen Bond Acceptor Count

Chemical Identifiers

Formula: C34H32FeN4O4
IUPAC Name: 3-[18-(2-carboxyethyl)-8,13-bis(ethenyl)-3,7,12,17-tetramethylporphyrin-21,24-diid-2-yl]propanoic acid;iron(2+)
Canonical SMILES: CC1=C(C2=CC3=C(C(=C([N-]3)C=C4C(=C(C(=N4)C=C5C(=C(C(=N5)C=C1[N-]2)C)C=C)C)C=C)C)CCC(=O)O)CCC(=O)O.[Fe+2]
InChI: InChI=1S/C34H34N4O4.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);/q;+2/p-2
InChIKey: KABFMIBPWCXCRK-UHFFFAOYSA-L

Cross-matching ID

PubChem CID: 26945
CAS Number: 14875-96-8
TTD ID: D0UU1I
VARIDT ID: DR00298

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Albendazole monooxygenase (CYP3A4)	TTXV4FI	CP3A4_HUMAN	Inhibitor	[2]
Arachidonate 5-lipoxygenase (5-LOX)	TT2J34L	LOX5_HUMAN	Inhibitor	[2]
Bacterial Flavohemoglobin (Bact hmp)	TTNAW8S	HMP_ECOLI	Inhibitor	[2]
Bacterial Fumarate reductase flavoprotein (Bact frdA)	TTHDSE2	FRDA_HELPY	Inhibitor	[2]
Cystathionine beta-synthase (CBS)	TTVZJ7G	CBS_HUMAN	Inhibitor	[2]
Heme oxygenase 1 (HMOX1)	TTI6V2A	HMOX1_HUMAN	Inhibitor	[2]
Hemoglobin (HB)	TTQO71U	HBA_HUMAN	Inhibitor	[2]
Mycobacterium Cytochrome p450 121 (MycB cyp121)	TTBK0PU	CP121_MYCBO	Inhibitor	[2]
Nitric-oxide synthase brain (NOS1)	TTZUFI5	NOS1_HUMAN	Inhibitor	[2]
Nitric-oxide synthase endothelial (NOS3)	TTCM4B3	NOS3_HUMAN	Inhibitor	[2]
Nitric-oxide synthase inducible (NOS2)	TTF10I9	NOS2_HUMAN	Inhibitor	[2]
Prostaglandin G/H synthase 1 (COX-1)	TT8NGED	PGH1_HUMAN	Inhibitor	[2]
Prostaglandin G/H synthase 2 (COX-2)	TTVKILB	PGH2_HUMAN	Inhibitor	[2]

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Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
5-aminolevulinate synthase, non-specific, mitochondrial (ALAS1)	OTQY6ZSF	HEM1_HUMAN	Gene/Protein Processing	[3]
Albumin (ALB)	OTVMM513	ALBU_HUMAN	Protein Interaction/Cellular Processes	[4]
Amyloid-beta precursor protein (APP)	OTKFD7R4	A4_HUMAN	Drug Response	[5]
ATP-binding cassette sub-family B member 6 (ABCB6)	OTPGZFES	ABCB6_HUMAN	Gene/Protein Processing	[6]
C-C motif chemokine 3 (CCL3)	OTW2H3ND	CCL3_HUMAN	Protein Interaction/Cellular Processes	[7]
Interleukin-1 beta (IL1B)	OT0DWXXB	IL1B_HUMAN	Protein Interaction/Cellular Processes	[7]
Lysozyme C (LYZ)	OTD7H0G6	LYSC_HUMAN	Protein Interaction/Cellular Processes	[7]
Metallothionein-1A (MT1A)	OTKBH52X	MT1A_HUMAN	Drug Response	[8]
Microprocessor complex subunit DGCR8 (DGCR8)	OT62LXE4	DGCR8_HUMAN	Drug Response	[9]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Gene/Protein Processing	[10]

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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease

Discovery agent

ICD Disease Classification

N.A.

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Prostaglandin G/H synthase 2 (COX-2)	DTT	PTGS2	7.93E-04	-0.29	-0.34
Prostaglandin G/H synthase 1 (COX-1)	DTT	PTGS1	3.97E-03	0.16	0.43

Molecular Expression Atlas (MEA)

MEA Detail

Jump to Detail Molecular Expression Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Heme (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Inotersen	DMJ93CT	Moderate	Increased risk of bleeding by the combination of Heme and Inotersen.	Amyloidosis [5D00]	[11]
Trastuzumab Emtansine	DMU1LXS	Moderate	Increased risk of bleeding by the combination of Heme and Trastuzumab Emtansine.	Breast cancer [2C60-2C6Y]	[11]
Regorafenib	DMHSY1I	Moderate	Increased risk of bleeding by the combination of Heme and Regorafenib.	Colorectal cancer [2B91]	[11]
Intedanib	DMSTA36	Moderate	Increased risk of bleeding by the combination of Heme and Intedanib.	Colorectal cancer [2B91]	[11]
Ardeparin	DMYRX8B	Moderate	Increased risk of bleeding by the combination of Heme and Ardeparin.	Coronary thrombosis [BA43]	[11]
Rivaroxaban	DMQMBZ1	Moderate	Increased risk of bleeding by the combination of Heme and Rivaroxaban.	Deep vein thrombosis [BD71]	[11]
Tazemetostat	DMWP1BH	Moderate	Increased risk of bleeding by the combination of Heme and Tazemetostat.	Follicular lymphoma [2A80]	[11]
Avapritinib	DMK2GZX	Moderate	Increased risk of bleeding by the combination of Heme and Avapritinib.	Gastrointestinal stromal tumour [2B5B]	[11]
Acalabrutinib	DM7GCVW	Moderate	Increased risk of bleeding by the combination of Heme and Acalabrutinib.	Mature B-cell lymphoma [2A85]	[11]
Ibrutinib	DMHZCPO	Moderate	Increased risk of bleeding by the combination of Heme and Ibrutinib.	Mature B-cell lymphoma [2A85]	[11]
Ponatinib	DMYGJQO	Moderate	Increased risk of bleeding by the combination of Heme and Ponatinib.	Mature B-cell lymphoma [2A85]	[11]
Panobinostat	DM58WKG	Moderate	Increased risk of bleeding by the combination of Heme and Panobinostat.	Multiple myeloma [2A83]	[11]
Fedratinib	DM4ZBK6	Moderate	Increased risk of bleeding by the combination of Heme and Fedratinib.	Myeloproliferative neoplasm [2A20]	[11]
Ruxolitinib	DM7Q98D	Moderate	Increased risk of bleeding by the combination of Heme and Ruxolitinib.	Myeloproliferative neoplasm [2A20]	[11]
Prasugrel	DM7MT6E	Moderate	Increased risk of bleeding by the combination of Heme and Prasugrel.	Myocardial infarction [BA41-BA43]	[11]
Vorapaxar	DMA16BR	Moderate	Increased risk of bleeding by the combination of Heme and Vorapaxar.	Myocardial infarction [BA41-BA43]	[11]
Caplacizumab	DMPUKA7	Moderate	Increased risk of bleeding by the combination of Heme and Caplacizumab.	Thrombocytopenia [3B64]	[11]
Apixaban	DM89JLN	Moderate	Increased risk of bleeding by the combination of Heme and Apixaban.	Thrombosis [DB61-GB90]	[11]
Cangrelor	DM8JRH0	Moderate	Increased risk of bleeding by the combination of Heme and Cangrelor.	Thrombosis [DB61-GB90]	[11]
Brilinta	DMBR01X	Moderate	Increased risk of bleeding by the combination of Heme and Brilinta.	Thrombosis [DB61-GB90]	[11]
Cabozantinib	DMIYDT4	Moderate	Increased risk of bleeding by the combination of Heme and Cabozantinib.	Thyroid cancer [2D10]	[11]
Betrixaban	DM2C4RF	Moderate	Increased risk of bleeding by the combination of Heme and Betrixaban.	Venous thromboembolism [BD72]	[11]
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⏷ Show the Full List of 22 DDI Information of This Drug

References

1	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 4349).
2	The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
3	Lon peptidase 1 (LONP1)-dependent breakdown of mitochondrial 5-aminolevulinic acid synthase protein by heme in human liver cells. J Biol Chem. 2011 Jul 29;286(30):26424-30. doi: 10.1074/jbc.M110.215772. Epub 2011 Jun 9.
4	Allosteric modulation of anti-HIV drug and ferric heme binding to human serum albumin. FEBS J. 2005 Dec;272(24):6287-96. doi: 10.1111/j.1742-4658.2005.05015.x.
5	Key roles for tyrosine 10 in a-heme complexes and its relevance to oxidative stress. Chem Res Toxicol. 2015 Mar 16;28(3):365-72. doi: 10.1021/tx5003035. Epub 2014 Sep 24.
6	Identification of a mammalian mitochondrial porphyrin transporter. Nature. 2006 Oct 5;443(7111):586-9. doi: 10.1038/nature05125. Epub 2006 Sep 27.
7	Role of 15-hydroxyeicosatetraenoic acid in hemozoin-induced lysozyme release from human adherent monocytes. Biofactors. 2013 May-Jun;39(3):304-14. doi: 10.1002/biof.1071. Epub 2013 Jan 28.
8	Metallothionein protects retinal pigment epithelial cells against apoptosis and oxidative stress. Exp Eye Res. 2002 Jan;74(1):83-92.
9	DiGeorge critical region 8 (DGCR8) is a double-cysteine-ligated heme protein. J Biol Chem. 2011 May 13;286(19):16716-25. doi: 10.1074/jbc.M110.180844. Epub 2011 Mar 21.
10	Cytotoxic effects of metal protoporphyrins in glioblastoma cells: roles of albumin, reactive oxygen species, and heme oxygenase-1. Toxicol Lett. 2008 Mar 15;177(2):97-107. doi: 10.1016/j.toxlet.2008.01.004. Epub 2008 Jan 15.
11	Product Information. Panhematin (hemin). Recordati Rare Diseases Inc, Lebanon, NJ.