T3DB: 1,10-Phenanthroline

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Gene Regulation Targets (6)XML

Targets (6)

Record Information

Version

2.0

Creation Date

2014-09-11 05:17:48 UTC

Update Date

2014-12-24 20:26:57 UTC

Accession Number

T3D4815

Identification

Common Name

1,10-Phenanthroline

Class

Small Molecule

Description

Phenanthroline is a heterocyclic organic compound. 1,10-Phenanthroline is an inhibitor of metallopeptidases, especially carboxypeptidase A. Inhibition of the enzyme occurs by removal and chelation of the metal ion required for catalytic activity, leaving an inactive apoenzyme. 1,10-Phenanthroline targets mainly zinc metallopeptidases, with a much lower affinity for calcium metallopeptidases.

Compound Type

Industrial/Workplace Toxin
Organic Compound
Synthetic Compound

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Not Available

Chemical Formula

C₁₂H₈N₂

Average Molecular Mass

180.205 g/mol

Monoisotopic Mass

180.069 g/mol

CAS Registry Number

66-71-7

IUPAC Name

1,10-phenanthroline

Traditional Name

phen

SMILES

C1=CC2=C(N=C1)C1=C(C=CC=N1)C=C2

InChI Identifier

InChI=1S/C12H8N2/c1-3-9-5-6-10-4-2-8-14-12(10)11(9)13-7-1/h1-8H

InChI Key

InChIKey=DGEZNRSVGBDHLK-UHFFFAOYSA-N

Chemical Taxonomy

Description

belongs to the class of organic compounds known as phenanthrolines. These are aromatic polycyclic compounds containing the phenanthroline skeleton, which is a derivative of phenanthrene, and consists of two pyridine rings non-linearly joined by a benzene ring.

Kingdom

Organic compounds

Super Class

Organoheterocyclic compounds

Class

Phenanthrolines

Sub Class

Not Available

Direct Parent

Phenanthrolines

Alternative Parents

Substituents

1,10-phenanthroline
Quinoline
Benzenoid
Pyridine
Heteroaromatic compound
Azacycle
Organic nitrogen compound
Organopnictogen compound
Hydrocarbon derivative
Organonitrogen compound
Aromatic heteropolycyclic compound

Molecular Framework

Aromatic heteropolycyclic compounds

External Descriptors

phenanthroline (CHEBI:44975 )
a small molecule (O-PHENANTHROLINE )

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Membrane

Biofluid Locations

Not Available

Tissue Locations

Not Available

Pathways

Not Available

Applications

Not Available

Biological Roles

Not Available

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	117°C
Boiling Point	> 300°C
Solubility	2690 mg/L (at 25°C)
LogP	1.78

Predicted Properties

Property	Value	Source
Water Solubility	0.13 g/L	ALOGPS
logP	2.31	ALOGPS
logP	2.29	ChemAxon
logS	-3.1	ALOGPS
pKa (Strongest Basic)	4.8	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	2	ChemAxon
Hydrogen Donor Count	0	ChemAxon
Polar Surface Area	25.78 Å²	ChemAxon
Rotatable Bond Count	0	ChemAxon
Refractivity	53.9 m³·mol⁻¹	ChemAxon
Polarizability	19.26 Å³	ChemAxon
Number of Rings	3	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	Deposition Date	View
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-0fai-1900000000-8bf54d7a505254cd0f42	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-003r-1900000000-bf66a4d49c83dd24535e	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-003r-4900000000-e878f31ffa5b4af39dfd	2017-09-12	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-001i-0900000000-eb76a0de05170e5f9dae	2021-09-23	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , positive	splash10-001i-0900000000-7bdef677e6a80f05aa75	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , positive	splash10-001i-0900000000-555e8d3f751a47049c5a	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , positive	splash10-001i-0900000000-c48df88a05c1dbab0adc	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , positive	splash10-001i-0900000000-07ee18512e76f5b25dd1	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , positive	splash10-0fb9-0900000000-7a08b5b37861250df6bd	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF , positive	splash10-001i-0900000000-94a0600a96f48f8aa145	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF , positive	splash10-0fc0-0900000000-0f2b71fb75d6e9f09b6c	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - ESI-ITFT , positive	splash10-001i-0900000000-29a83efe3a4c61b6e760	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - ESI-ITFT , positive	splash10-001i-0900000000-f6eedb340d4cf4ab269f	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - ESI-ITFT , positive	splash10-001i-0900000000-b8ee2e5a776aecb532ca	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - ESI-ITFT , positive	splash10-00di-0900000000-88682d0eaadc3985ae6f	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - ESI-ITFT , positive	splash10-001i-0900000000-5c3af3894358cf9d55fc	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - ESI-ITFT , positive	splash10-001i-0900000000-29a83efe3a4c61b6e760	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - ESI-ITFT , positive	splash10-001i-0900000000-e7952d19ca3578ac4501	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - ESI-ITFT , positive	splash10-001i-0900000000-e7952d19ca3578ac4501	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - ESI-ITFT , positive	splash10-001i-0900000000-62142b81fd0b92ba0c9d	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - ESI-ITFT , positive	splash10-001i-0900000000-9cbaa490715b11601fdc	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - ESI-ITFT , positive	splash10-001i-0900000000-7095641d365002c9b143	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - ESI-ITFT , positive	splash10-0f89-0900000000-c2a7113134a8fdaed496	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - ESI-ITFT , positive	splash10-0fb9-0900000000-b0fd72c65f3813200a20	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - ESI-ITFT , positive	splash10-004i-2900000000-4ffad714811e85731892	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - APCI-ITFT , positive	splash10-001i-0900000000-e090efe0cddbe7929cb2	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - APCI-ITFT , positive	splash10-001i-0900000000-4fc72504435ed95451ac	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - APCI-ITFT , positive	splash10-001i-0900000000-ea4fdf798419a11217f2	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - APCI-ITFT , positive	splash10-001i-0900000000-e090efe0cddbe7929cb2	2017-09-14	View Spectrum
MS	Mass Spectrum (Electron Ionization)	splash10-001i-1900000000-e3edab983e41e183110a	2014-09-20	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 300 MHz, CDCl₃, experimental)	Not Available	2014-09-20	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 25.16 MHz, CDCl₃, experimental)	Not Available	2014-09-23	View Spectrum

Toxicity Profile

Route of Exposure

Not Available

Mechanism of Toxicity

Not Available

Metabolism

Not Available

Toxicity Values

Not Available

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

No indication of carcinogenicity to humans (not listed by IARC).

Uses/Sources

Not Available

Minimum Risk Level

Not Available

Health Effects

Not Available

Symptoms

Not Available

Treatment

Not Available

Normal Concentrations

Not Available

Abnormal Concentrations

Not Available

External Links

DrugBank ID

DB02365

HMDB ID

Not Available

PubChem Compound ID

1318

ChEMBL ID

Not Available

ChemSpider ID

1278

KEGG ID

C00604

UniProt ID

Not Available

OMIM ID

ChEBI ID

476

BioCyc ID

Not Available

CTD ID

Not Available

Stitch ID

Not Available

PDB ID

Not Available

ACToR ID

Not Available

Wikipedia Link

Not Available

References

Synthesis Reference

Judith N. Burstyn, Omar Green, Bhavesh A. Gandhi, “BISCOPPER COMPLEXES, METHODS OF SYNTHESIS, AND USES THEROF.” U.S. Patent US20080206890, issued August 28, 2008.

MSDS

T3D4815.pdf

General References

Not Available

Gene Regulation

Up-Regulated Genes

Not Available

Down-Regulated Genes

Not Available

Targets

Target Details

1. Thyroid hormone receptor alpha

General Function:: Zinc ion binding
Specific Function:: Isoform Alpha-1: Nuclear hormone receptor that can act as a repressor or activator of transcription. High affinity receptor for thyroid hormones, including triiodothyronine and thyroxine.Isoform Alpha-2: Does not bind thyroid hormone and functions as a weak dominant negative inhibitor of thyroid hormone action.
Gene Name:: THRA
Uniprot ID:: P10827
Molecular Weight:: 54815.055 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
AC50	0.238 uM	NVS_NR_hTRa	Novascreen

References

Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]

Target Details

2. Androgen receptor

General Function:: Zinc ion binding
Specific Function:: Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Transcription factor activity is modulated by bound coactivator and corepressor proteins. Transcription activation is down-regulated by NR0B2. Activated, but not phosphorylated, by HIPK3 and ZIPK/DAPK3.
Gene Name:: AR
Uniprot ID:: P10275
Molecular Weight:: 98987.9 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
AC50	0.528 uM	Tox21_AR_BLA_Antagonist_ratio	Tox21/NCGC

References

Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]

Target Details

3. Estrogen receptor

General Function:: Zinc ion binding
Specific Function:: Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Isoform 3 is involved in activation of NOS3 and endothelial nitric oxide production. Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full length receptor. Essential for MTA1-mediated transcriptional regulation of BRCA1 and BCAS3. Isoform 3 can bind to ERE and inhibit isoform 1.
Gene Name:: ESR1
Uniprot ID:: P03372
Molecular Weight:: 66215.45 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
AC50	3.21 uM	Tox21_ERa_BLA_Antagonist_ratio	Tox21/NCGC
AC50	3.83 uM	Tox21_ERa_LUC_BG1_Antagonist	Tox21/NCGC

References

Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]

Target Details

4. Aromatase

General Function:: Oxygen binding
Specific Function:: Catalyzes the formation of aromatic C18 estrogens from C19 androgens.
Gene Name:: CYP19A1
Uniprot ID:: P11511
Molecular Weight:: 57882.48 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
AC50	3.22 uM	Tox21_Aromatase_Inhibition	Tox21/NCGC

References

Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]

Target Details

5. Hypoxia-inducible factor 1-alpha

General Function:: Ubiquitin protein ligase binding
Specific Function:: Functions as a master transcriptional regulator of the adaptive response to hypoxia. Under hypoxic conditions, activates the transcription of over 40 genes, including erythropoietin, glucose transporters, glycolytic enzymes, vascular endothelial growth factor, HILPDA, and other genes whose protein products increase oxygen delivery or facilitate metabolic adaptation to hypoxia. Plays an essential role in embryonic vascularization, tumor angiogenesis and pathophysiology of ischemic disease. Binds to core DNA sequence 5'-[AG]CGTG-3' within the hypoxia response element (HRE) of target gene promoters. Activation requires recruitment of transcriptional coactivators such as CREBPB and EP300. Activity is enhanced by interaction with both, NCOA1 or NCOA2. Interaction with redox regulatory protein APEX seems to activate CTAD and potentiates activation by NCOA1 and CREBBP. Involved in the axonal distribution and transport of mitochondria in neurons during hypoxia.
Gene Name:: HIF1A
Uniprot ID:: Q16665
Molecular Weight:: 92669.595 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
AC50	7.27 uM	ATG_HIF1a_CIS	Attagene

References

Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]

Target Details

6. Oxysterols receptor LXR-beta

General Function:: Zinc ion binding
Specific Function:: Nuclear receptor. Binds preferentially to double-stranded oligonucleotide direct repeats having the consensus half-site sequence 5'-AGGTCA-3' and 4-nt spacing (DR-4). Regulates cholesterol uptake through MYLIP-dependent ubiquitination of LDLR, VLDLR and LRP8; DLDLR and LRP8. Interplays functionally with RORA for the regulation of genes involved in liver metabolism (By similarity). Exhibits a ligand-dependent transcriptional activation activity (PubMed:25661920).
Gene Name:: NR1H2
Uniprot ID:: P55055
Molecular Weight:: 50973.375 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
AC50	8.04 uM	ATG_LXRb_TRANS	Attagene

References

Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]

1,10-Phenanthroline (T3D4815)

Structure for T3D4815: 1,10-Phenanthroline

Targets

Binding/Activity Constants

References

Binding/Activity Constants

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Binding/Activity Constants

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Binding/Activity Constants

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