Target Information
Target General Information | Top | |||||
---|---|---|---|---|---|---|
Target ID |
T67801
(Former ID: TTDR01148)
|
|||||
Target Name |
Lactotransferrin (LTF)
|
|||||
Synonyms |
Talalactoferrin; Lactoferrin; LF; Growth-inhibiting protein 12; GIG12
Click to Show/Hide
|
|||||
Gene Name |
LTF
|
|||||
Target Type |
Clinical trial target
|
[1] | ||||
Disease | [+] 1 Target-related Diseases | + | ||||
1 | Diabetic foot ulcer [ICD-11: BD54] | |||||
Function |
Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate.
Click to Show/Hide
|
|||||
BioChemical Class |
Transferrin
|
|||||
UniProt ID | ||||||
EC Number |
EC 3.4.21.-
|
|||||
Sequence |
MKLVFLVLLFLGALGLCLAGRRRSVQWCAVSQPEATKCFQWQRNMRKVRGPPVSCIKRDS
PIQCIQAIAENRADAVTLDGGFIYEAGLAPYKLRPVAAEVYGTERQPRTHYYAVAVVKKG GSFQLNELQGLKSCHTGLRRTAGWNVPIGTLRPFLNWTGPPEPIEAAVARFFSASCVPGA DKGQFPNLCRLCAGTGENKCAFSSQEPYFSYSGAFKCLRDGAGDVAFIRESTVFEDLSDE AERDEYELLCPDNTRKPVDKFKDCHLARVPSHAVVARSVNGKEDAIWNLLRQAQEKFGKD KSPKFQLFGSPSGQKDLLFKDSAIGFSRVPPRIDSGLYLGSGYFTAIQNLRKSEEEVAAR RARVVWCAVGEQELRKCNQWSGLSEGSVTCSSASTTEDCIALVLKGEADAMSLDGGYVYT AGKCGLVPVLAENYKSQQSSDPDPNCVDRPVEGYLAVAVVRRSDTSLTWNSVKGKKSCHT AVDRTAGWNIPMGLLFNQTGSCKFDEYFSQSCAPGSDPRSNLCALCIGDEQGENKCVPNS NERYYGYTGAFRCLAENAGDVAFVKDVTVLQNTDGNNNEAWAKDLKLADFALLCLDGKRK PVTEARSCHLAMAPNHAVVSRMDKVERLKQVLLHQQAKFGRNGSDCPDKFCLFQSETKNL LFNDNTECLARLHGKTTYEKYLGPQYVAGITNLKKCSTSPLLEACEFLRK Click to Show/Hide
|
|||||
3D Structure | Click to Show 3D Structure of This Target | PDB |
Drugs and Modes of Action | Top | |||||
---|---|---|---|---|---|---|
Clinical Trial Drug(s) | [+] 2 Clinical Trial Drugs | + | ||||
1 | Talactoferrin | Drug Info | Phase 3 | Diabetic foot ulcer | [2] | |
2 | HLF 1-11 | Drug Info | Phase 1/2 | Bacterial infection | [3] | |
Discontinued Drug(s) | [+] 1 Discontinued Drugs | + | ||||
1 | Nimesulide | Drug Info | Terminated | Metastatic colorectal cancer | [4] | |
Mode of Action | [+] 2 Modes of Action | + | ||||
Inhibitor | [+] 8 Inhibitor drugs | + | ||||
1 | Parecoxib | Drug Info | [1] | |||
2 | Nimesulide | Drug Info | [7] | |||
3 | 3h-Indole-5,6-Diol | Drug Info | [8] | |||
4 | Alpha-D-Fucose | Drug Info | [8] | |||
5 | Alpha-D-Mannose | Drug Info | [8] | |||
6 | Fucose | Drug Info | [8] | |||
7 | Lauric Acid | Drug Info | [8] | |||
8 | Nitrilotriacetic Acid | Drug Info | [8] | |||
Modulator | [+] 2 Modulator drugs | + | ||||
1 | Talactoferrin | Drug Info | [5] | |||
2 | HLF 1-11 | Drug Info | [6] |
Cell-based Target Expression Variations | Top | |||||
---|---|---|---|---|---|---|
Cell-based Target Expression Variations |
Drug Binding Sites of Target | Top | |||||
---|---|---|---|---|---|---|
Ligand Name: Lauric acid | Ligand Info | |||||
Structure Description | Structure of C12-LF11 bound to the DPC micelles | PDB:2GMC | ||||
Method | Solution NMR | Resolution | N.A. | Mutation | No | [9] |
PDB Sequence |
FQWQRNIRKV
10 R
|
|||||
|
||||||
Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
Click to View More Binding Site Information of This Target with Different Ligands |
Different Human System Profiles of Target | Top |
---|---|
Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Tissue Distribution
Biological Network Descriptors
|
There is no similarity protein (E value < 0.005) for this target
|
Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
|
Degree | 1 | Degree centrality | 1.07E-04 | Betweenness centrality | 0.00E+00 |
---|---|---|---|---|---|
Closeness centrality | 1.82E-01 | Radiality | 1.30E+01 | Clustering coefficient | 0.00E+00 |
Neighborhood connectivity | 1.10E+01 | Topological coefficient | 1.00E+00 | Eccentricity | 12 |
Download | Click to Download the Full PPI Network of This Target | ||||
Drug Property Profile of Target | Top | |
---|---|---|
(1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
|
||
(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
|
||
(5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
|
||
"RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five |
Co-Targets | Top | |||||
---|---|---|---|---|---|---|
Co-Targets |
Target Regulators | Top | |||||
---|---|---|---|---|---|---|
Target-regulating microRNAs |
Target Affiliated Biological Pathways | Top | |||||
---|---|---|---|---|---|---|
NetPath Pathway | [+] 2 NetPath Pathways | + | ||||
1 | TGF_beta_Receptor Signaling Pathway | |||||
2 | TCR Signaling Pathway | |||||
Reactome | [+] 2 Reactome Pathways | + | ||||
1 | ROS production in response to bacteria | |||||
2 | Amyloid formation | |||||
WikiPathways | [+] 1 WikiPathways | + | ||||
1 | Latent infection of Homo sapiens with Mycobacterium tuberculosis |
References | Top | |||||
---|---|---|---|---|---|---|
REF 1 | The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. | |||||
REF 2 | ClinicalTrials.gov (NCT00706862) Safety and Efficacy of Talactoferrin in Addition to Standard Chemotherapy in Patients With Non-small Cell Lung Cancer. U.S. National Institutes of Health. | |||||
REF 3 | ClinicalTrials.gov (NCT00509847) A Study on the Tolerability and Early Efficacy of hLF1-11 in Patients With Bacteremia Due to S. Epidermidis. U.S. National Institutes of Health. | |||||
REF 4 | Clinical pipeline report, company report or official report of Genentech (2011). | |||||
REF 5 | Talactoferrin alfa, a recombinant human lactoferrin promotes healing of diabetic neuropathic ulcers: a phase 1/2 clinical study. Am J Surg. 2007 Jan;193(1):49-54. | |||||
REF 6 | The synthetic N-terminal peptide of human lactoferrin, hLF(1-11), is highly effective against experimental infection caused by multidrug-resistant Acinetobacter baumannii. Antimicrob Agents Chemother. 2004 Dec;48(12):4919-21. | |||||
REF 7 | Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. | |||||
REF 8 | How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | |||||
REF 9 | The acyl group as the central element of the structural organization of antimicrobial lipopeptide. J Am Chem Soc. 2007 Feb 7;129(5):1022-3. |
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.