Target Information
| Target General Information | Top | |||||
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| Target ID |
T63068
(Former ID: TTDS00336)
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| Target Name |
Serum albumin (ALB)
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| Synonyms |
Serum albumin
Click to Show/Hide
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| Gene Name |
ALB
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 9 Target-related Diseases | + | ||||
| 1 | Aneurysm/dissection [ICD-11: BD50] | |||||
| 2 | Bowel habit change [ICD-11: ME05] | |||||
| 3 | Cholelithiasis [ICD-11: DC11] | |||||
| 4 | Inborn energy metabolism error [ICD-11: 5C53] | |||||
| 5 | Irritable bowel syndrome [ICD-11: DD91] | |||||
| 6 | Preprocedural examination [ICD-11: QA0B] | |||||
| 7 | Rheumatoid arthritis [ICD-11: FA20] | |||||
| 8 | Schizophrenia [ICD-11: 6A20] | |||||
| 9 | Unspecific body region injury [ICD-11: ND56] | |||||
| Function |
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloidal osmotic pressure of blood. Major zinc transporter in plasma, typically binds about 80% of all plasma zinc.
Click to Show/Hide
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| UniProt ID | ||||||
| Sequence |
MKWVTFISLLFLFSSAYSRGVFRRDAHKSEVAHRFKDLGEENFKALVLIAFAQYLQQCPF
EDHVKLVNEVTEFAKTCVADESAENCDKSLHTLFGDKLCTVATLRETYGEMADCCAKQEP ERNECFLQHKDDNPNLPRLVRPEVDVMCTAFHDNEETFLKKYLYEIARRHPYFYAPELLF FAKRYKAAFTECCQAADKAACLLPKLDELRDEGKASSAKQRLKCASLQKFGERAFKAWAV ARLSQRFPKAEFAEVSKLVTDLTKVHTECCHGDLLECADDRADLAKYICENQDSISSKLK ECCEKPLLEKSHCIAEVENDEMPADLPSLAADFVESKDVCKNYAEAKDVFLGMFLYEYAR RHPDYSVVLLLRLAKTYETTLEKCCAAADPHECYAKVFDEFKPLVEEPQNLIKQNCELFE QLGEYKFQNALLVRYTKKVPQVSTPTLVEVSRNLGKVGSKCCKHPEAKRMPCAEDYLSVV LNQLCVLHEKTPVSDRVTKCCTESLVNRRPCFSALEVDETYVPKEFNAETFTFHADICTL SEKERQIKKQTALVELVKHKPKATKEQLKAVMDDFAAFVEKCCKADDKETCFAEEGKKLV AASQAALGL Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| ADReCS ID | BADD_A00127 ; BADD_A02053 ; BADD_A02603 | |||||
| HIT2.0 ID | T18YXD | |||||
| Drugs and Modes of Action | Top | |||||
|---|---|---|---|---|---|---|
| Approved Drug(s) | [+] 9 Approved Drugs | + | ||||
| 1 | Albumin Human | Drug Info | Approved | Hypoalbuminemia | [2] | |
| 2 | Bismuth | Drug Info | Approved | Diarrhea | [3] | |
| 3 | EVANS BLUE | Drug Info | Approved | Abdominal aortic aneurysm | [4] | |
| 4 | Gadobenate Dimeglumine | Drug Info | Approved | Schizophrenia | [2], [5], [6] | |
| 5 | Gadofosveset | Drug Info | Approved | Imaging | [7] | |
| 6 | Iodipamide | Drug Info | Approved | Gallbladder disease | [2], [8], [9] | |
| 7 | Oxyphenbutazone | Drug Info | Approved | Arthritis | [2] | |
| 8 | Sodium lauryl sulfate | Drug Info | Approved | Constipation | [10] | |
| 9 | SPI-1005 | Drug Info | Approved | Reperfusion injury | [11] | |
| Clinical Trial Drug(s) | [+] 3 Clinical Trial Drugs | + | ||||
| 1 | Activated recombinant FVII-albumin fusion protein | Drug Info | Phase 2/3 | Hemophilia | [12] | |
| 2 | Vobarilizumab | Drug Info | Phase 2 | Rheumatoid arthritis | [13] | |
| 3 | RU-101 | Drug Info | Phase 1/2 | Xerophthalmia | [14] | |
| Mode of Action | [+] 3 Modes of Action | + | ||||
| Modulator | [+] 6 Modulator drugs | + | ||||
| 1 | Albumin Human | Drug Info | [15] | |||
| 2 | EVANS BLUE | Drug Info | [4] | |||
| 3 | Gadofosveset | Drug Info | [7] | |||
| 4 | Oxyphenbutazone | Drug Info | [18] | |||
| 5 | Activated recombinant FVII-albumin fusion protein | Drug Info | [21] | |||
| 6 | RU-101 | Drug Info | [23] | |||
| Binder | [+] 5 Binder drugs | + | ||||
| 1 | Bismuth | Drug Info | [16] | |||
| 2 | Gadobenate Dimeglumine | Drug Info | [1] | |||
| 3 | Iodipamide | Drug Info | [17] | |||
| 4 | Sodium lauryl sulfate | Drug Info | [19] | |||
| 5 | SPI-1005 | Drug Info | [20] | |||
| Inhibitor | [+] 1 Inhibitor drugs | + | ||||
| 1 | Vobarilizumab | Drug Info | [22] | |||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: Cisplatin | Ligand Info | |||||
| Structure Description | Crystal structure of HSA-Myr complex soaked with cisplatin for one week | PDB:7WOJ | ||||
| Method | X-ray diffraction | Resolution | 2.89 Å | Mutation | No | [24] |
| PDB Sequence |
VAHRFKDLGE
16 ENFKALVLIA26 FAQYLQQCPF36 EDHVKLVNEV46 TEFAKTCVAD56 ESAENCDLHT 68 LFGDKLCTVA78 TLRETYGEMA88 DCCAKQEPER98 NECFLQHKDD108 NPNLPRLVRP 118 EVDVMCTAFH128 DNEETFLKKY138 LYEIARRHPY148 FYAPELLFFA158 KRYKAAFTEC 168 CQAADKAACL178 LPKLDELRDE188 GKASSAKQRL198 KCASLQKFGE208 RAFKAWAVAR 218 LSQRFPKAEF228 AEVSKLVTDL238 TKVHTECCHG248 DLLECADDRA258 DLAKYICENQ 268 DSISSKLKEC278 CEKPLLEKSH288 CIAEVENDEM298 PADLPSLAAD308 FVESKDVCKN 318 YAEAKDVFLG328 MFLYEYARRH338 PDYSVVLLLR348 LAKTYETTLE358 KCCAAADPHE 368 CYFDEFKPLV381 EEPQNLIKQN391 CELFEQLGEY401 KFQNALLVRY411 TKKVPQVSTP 421 TLVEVSRNLG431 KVGSKCCKHP441 EAKRMPCAED451 YLSVVLNQLC461 VLHEKTPVSD 471 RVTKCCTESL481 VNRRPCFSAL491 EVDETYVPKE501 FNAETFTFHA511 DICTLSEKER 521 QIKKQTALVE531 LVKHKPKATK541 EQLKAVMDDF551 AAFVEKCETC567 FAEEGKKLVA 577 ASQAALG
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GLU86
3.804
MET87
4.492
GLN104
3.683
HIS105
1.817
ARG114
3.311
PHE127
3.839
HIS128
2.142
ILE142
4.827
ARG145
3.513
HIS146
1.943
CYS169
4.865
GLU188
4.771
LYS190
4.619
PHE228
3.287
CYS246
4.692
HIS247
2.304
MET298
2.096
ASP308
3.468
PHE309
3.521
PHE326
4.256
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: Diclofenac | Ligand Info | |||||
| Structure Description | Human serum albumin complexed with palmitic acid and diclofenac | PDB:4Z69 | ||||
| Method | X-ray diffraction | Resolution | 2.19 Å | Mutation | No | [25] |
| PDB Sequence |
HKSEVAHRFK
12 DLGEENFKAL22 VLIAFAQYLQ32 QCPFEDHVKL42 VNEVTEFAKT52 CVADESAENC 62 DKSLHTLFGD72 KLCTVATLRE82 TYGEMADCCA92 KQEPERNECF102 LQHKDDNPNL 112 PRLVRPEVDV122 MCTAFHDNEE132 TFLKKYLYEI142 ARRHPYFYAP152 ELLFFAKRYK 162 AAFTECCQAA172 DKAACLLPKL182 DELRDEGKAS192 SAKQRLKCAS202 LQKFGERAFK 212 AWAVARLSQR222 FPKAEFAEVS232 KLVTDLTKVH242 TECCHGDLLE252 CADDRADLAK 262 YICENQDSIS272 SKLKECCEKP282 LLEKSHCIAE292 VENDEMPADL302 PSLAADFVES 312 KDVCKNYAEA322 KDVFLGMFLY332 EYARRHPDYS342 VVLLLRLAKT352 YETTLEKCCA 362 AADPHECYAK372 VFDEFKPLVE382 EPQNLIKQNC392 ELFEQLGEYK402 FQNALLVRYT 412 KKVPQVSTPT422 LVEVSRNLGK432 VGSKCCKHPE442 AKRMPCAEDY452 LSVVLNQLCV 462 LHEKTPVSDR472 VTKCCTESLV482 NRRPCFSALE492 VDETYVPKEF502 NAETFTFHAD 512 ICTLSEKERQ522 IKKQTALVEL532 VKHKPKATKE542 QLKAVMDDFA552 AFVEKCCKAD 562 DKETCFAEEG572 KKLVAASQAA582 L
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ILE142
2.997
HIS146
2.823
PHE149
3.469
LEU154
3.456
PHE157
4.255
TYR161
2.534
LEU185
3.828
ARG186
3.168
GLY189
3.305
LYS190
3.106
SER193
4.372
LYS199
3.159
SER202
3.190
LEU203
3.257
PHE206
3.180
GLY207
3.938
ALA210
2.900
PHE211
2.995
TRP214
3.182
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| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
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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).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
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
Human Pathway Affiliation
Biological Network Descriptors
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There is no similarity protein (E value < 0.005) for this target
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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.
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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| Thyroid hormone synthesis | hsa04918 | Affiliated Target |
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| Class: Organismal Systems => Endocrine system | Pathway Hierarchy | ||
| Degree | 22 | Degree centrality | 2.36E-03 | Betweenness centrality | 2.72E-03 |
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| Closeness centrality | 2.20E-01 | Radiality | 1.39E+01 | Clustering coefficient | 6.49E-02 |
| Neighborhood connectivity | 1.60E+01 | Topological coefficient | 5.81E-02 | Eccentricity | 11 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "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 | |||||
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| Co-Targets | ||||||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Regulators | Top | |||||
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| Target-regulating microRNAs | ||||||
| Target Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| PID Pathway | [+] 1 PID Pathways | + | ||||
| 1 | FOXA2 and FOXA3 transcription factor networks | |||||
| Reactome | [+] 4 Reactome Pathways | + | ||||
| 1 | Platelet degranulation | |||||
| 2 | Recycling of bile acids and salts | |||||
| 3 | HDL-mediated lipid transport | |||||
| 4 | Scavenging of heme from plasma | |||||
| WikiPathways | [+] 8 WikiPathways | + | ||||
| 1 | Human Complement System | |||||
| 2 | Binding and Uptake of Ligands by Scavenger Receptors | |||||
| 3 | Lipid digestion, mobilization, and transport | |||||
| 4 | Transport of vitamins, nucleosides, and related molecules | |||||
| 5 | Bile acid and bile salt metabolism | |||||
| 6 | Folate Metabolism | |||||
| 7 | Vitamin B12 Metabolism | |||||
| 8 | Selenium Micronutrient Network | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Protocol design for high relaxivity contrast agents in MR imaging of the CNS. Eur Radiol. 2006 Nov;16 Suppl 7:M3-7. | |||||
| REF 2 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
| REF 3 | The effect of histamine H2-receptor blockade on bismuth absorption from three ulcer-healing compounds. Gastroenterology. 1991 Oct;101(4):889-94. | |||||
| REF 4 | The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954. | |||||
| REF 5 | 2004 approvals: the demise of the blockbuster. Nat Rev Drug Discov. 2005 Feb;4(2):93-4. | |||||
| REF 6 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 021357. | |||||
| REF 7 | 2008 FDA drug approvals. Nat Rev Drug Discov. 2009 Feb;8(2):93-6. | |||||
| REF 8 | 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: 7400). | |||||
| REF 9 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 009321. | |||||
| REF 10 | Drug information of Sodium lauryl sulfate, 2008. eduDrugs. | |||||
| REF 11 | Advances in ischemic stroke treatment: neuroprotective and combination therapies. Expert Opin Emerg Drugs. 2007 Mar;12(1):97-112. | |||||
| REF 12 | ClinicalTrials.gov (NCT02484638) Study of Recombinant Factor VIIa Fusion Protein (rVIIa-FP, CSL689) for On-demand Treatment of Bleeding Episodes in Patients With Hemophilia A or B With Inhibitors. | |||||
| REF 13 | ClinicalTrials.gov (NCT02518620) An Open-Label Extension Study Assessing the Long-Term Efficacy and Safety of ALX-0061 in Subjects With Rheumatoid Arthritis. U.S. National Institutes of Health. | |||||
| REF 14 | ClinicalTrials.gov (NCT01843894) A Phase 1/2, RU-101 Ophthalmic Solution in Patients With Severe Dry Eye. U.S. National Institutes of Health. | |||||
| REF 15 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. | |||||
| REF 16 | Competitive binding of bismuth to transferrin and albumin in aqueous solution and in blood plasma. J Biol Chem. 2001 Mar 23;276(12):8829-35. | |||||
| REF 17 | Determining binding sites of drugs on human serum albumin using FIA-QCM. Biosens Bioelectron. 2008 Sep 15;24(1):48-54. | |||||
| REF 18 | Effect of albumin conformation on binding of phenylbutazone and oxyphenbutazone to human serum albumin. J Pharm Sci. 1982 Feb;71(2):241-4. | |||||
| REF 19 | Some properties of the interaction between 2,2'-diselenadibenzoic acid and serum albumins. J Pharm Biomed Anal. 2005 Sep 1;39(1-2):263-7. | |||||
| REF 20 | Transport of ebselen in plasma and its transfer to binding sites in the hepatocyte. Biochem Pharmacol. 1994 Sep 15;48(6):1137-44. | |||||
| REF 21 | ClinicalTrials.gov (NCT01542619) A Safety and Pharmacokinetics Study of a Recombinant Fusion Protein Linking Coagulation Factor VIIa With Albumin (rVIIa-FP) in Healthy Male Volunteers. U.S. National Institutes of Health. | |||||
| REF 22 | Clinical pipeline report, company report or official report of Ablynx. | |||||
| REF 23 | Albumin as a tear supplement in the treatment of severe dry eye. Br J Ophthalmol. 2003 October; 87(10): 1279-1283. | |||||
| REF 24 | Crystallographic analysis of interaction between cisplatin and human serum albumin: Effect of fatty acid. Int J Biol Macromol. 2022 Sep 1;216:172-178. | |||||
| REF 25 | Structural basis of non-steroidal anti-inflammatory drug diclofenac binding to human serum albumin. Chem Biol Drug Des. 2015 Nov;86(5):1178-84. | |||||
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