Target Information
| Target General Information | Top | |||||
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| Target ID |
T66011
(Former ID: TTDI02354)
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| Target Name |
Complement factor B (CFB)
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| Synonyms |
Properdin factor B; PBF2; Glycinerich beta glycoprotein; Glycine-rich beta glycoprotein; GBG; Complement factor B Bb fragment; C3/C5 convertase; BFD; BF
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| Gene Name |
CFB
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Haemolytic anemia [ICD-11: 3A20-3A2Z] | |||||
| Function |
Factor B which is part of the alternate pathway of the complement system is cleaved by factor D into 2 fragments: Ba and Bb. Bb, a serine protease, then combines with complement factor 3b to generate the C3 or C5 convertase. It has also been implicated in proliferation and differentiation of preactivated B-lymphocytes, rapid spreading of peripheral blood monocytes, stimulation of lymphocyte blastogenesis and lysis of erythrocytes. Ba inhibits the proliferation of preactivated B-lymphocytes.
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| BioChemical Class |
Peptidase
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| UniProt ID | ||||||
| EC Number |
EC 3.4.21.47
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| Sequence |
MGSNLSPQLCLMPFILGLLSGGVTTTPWSLARPQGSCSLEGVEIKGGSFRLLQEGQALEY
VCPSGFYPYPVQTRTCRSTGSWSTLKTQDQKTVRKAECRAIHCPRPHDFENGEYWPRSPY YNVSDEISFHCYDGYTLRGSANRTCQVNGRWSGQTAICDNGAGYCSNPGIPIGTRKVGSQ YRLEDSVTYHCSRGLTLRGSQRRTCQEGGSWSGTEPSCQDSFMYDTPQEVAEAFLSSLTE TIEGVDAEDGHGPGEQQKRKIVLDPSGSMNIYLVLDGSDSIGASNFTGAKKCLVNLIEKV ASYGVKPRYGLVTYATYPKIWVKVSEADSSNADWVTKQLNEINYEDHKLKSGTNTKKALQ AVYSMMSWPDDVPPEGWNRTRHVIILMTDGLHNMGGDPITVIDEIRDLLYIGKDRKNPRE DYLDVYVFGVGPLVNQVNINALASKKDNEQHVFKVKDMENLEDVFYQMIDESQSLSLCGM VWEHRKGTDYHKQPWQAKISVIRPSKGHESCMGAVVSEYFVLTAAHCFTVDDKEHSIKVS VGGEKRDLEIEVVLFHPNYNINGKKEAGIPEFYDYDVALIKLKNKLKYGQTIRPICLPCT EGTTRALRLPPTTTCQQQKEELLPAQDIKALFVSEEEKKLTRKEVYIKNGDKKGSCERDA QYAPGYDKVKDISEVVTPRFLCTGGVSPYADPNTCRGDSGGPLIVHKRSRFIQVGVISWG VVDVCKNQKRQKQVPAHARDFHINLFQVLPWLKEKLQDEDLGFL Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| Drugs and Modes of Action | Top | |||||
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| Approved Drug(s) | [+] 1 Approved Drugs | + | ||||
| 1 | Iptacopan | Drug Info | Approved | Paroxysmal nocturnal haemoglobinuria | [1] | |
| Clinical Trial Drug(s) | [+] 3 Clinical Trial Drugs | + | ||||
| 1 | LPN023 | Drug Info | Phase 2 | IgA nephropathy | [2] | |
| 2 | RG6299 | Drug Info | Phase 2 | IgA nephropathy | [3] | |
| 3 | SAR443809 | Drug Info | Phase 1 | Discovery agent | [4] | |
| Discontinued Drug(s) | [+] 1 Discontinued Drugs | + | ||||
| 1 | CAB-2 | Drug Info | Discontinued in Phase 1 | Coronary artery disease | [5] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Inhibitor | [+] 4 Inhibitor drugs | + | ||||
| 1 | Iptacopan | Drug Info | [1] | |||
| 2 | LPN023 | Drug Info | [6] | |||
| 3 | CAB-2 | Drug Info | [7] | |||
| 4 | PMID19743866C51 | Drug Info | [9] | |||
| 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: Diisopropylphosphono Group | Ligand Info | |||||
| Structure Description | Crystal Structure Analysis of the Bb segment of Factor B complexed with Di-isopropyl-phosphate (DIP) | PDB:1RS0 | ||||
| Method | X-ray diffraction | Resolution | 2.60 Å | Mutation | Yes | [10] |
| PDB Sequence |
SMNIYLVLDG
252 SDSIGASNFT262 GAKKVLVNLI272 EKVASYGVKP282 RYGLVTYATY292 PKIWVKVSEA 302 DSSNADWVTK312 QLNEINYEDH322 KLKSGTNTKK332 ALQAVYSMMS342 WPGWNRTRHV 358 IILMTDGLHN368 MGGDPITVID378 EIRDLLYIGK388 DRNPREDYLD399 VYVFGVGPLV 409 NQVNINALAS419 KKDNEQHVCK429 VKDMECLEDV439 FYQMIDESQS449 LSLCGMVWEH 459 RKGTDYHKQP469 WQAKISVIRK481 GHESCMGAVV491 SEYFVLTAAH501 CFTVDDKEHS 511 IKVSVGGEKR521 DLEIEVVLFH531 PNYNINGKKE541 AGIPEFYDYD551 VALIKLKNKL 561 KYGQTIRPIC571 LPCTEGTTRA581 LRLPPTTTCQ591 QQKEELLPAQ601 DIKALFVSEE 611 EKKLTRKEVY621 IKNGDKKGSC631 ERDAQYAPGY641 DKVKDISEVV651 TPRFLCTGGV 661 SPYADPNTCR671 GDSGGPLIVH681 KRSRFIQVGV691 ISWGVVDVCV709 PAHARDFHIN 719 LFQVLPWLKE729 KLQDEDLGFL739
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| Ligand Name: 4-Guanidinobenzoic acid | Ligand Info | |||||
| Structure Description | Crystal Structure Analysis of the Bb segment of Factor B complexed with 4-guanidinobenzoic acid | PDB:1RTK | ||||
| Method | X-ray diffraction | Resolution | 2.30 Å | Mutation | Yes | [10] |
| PDB Sequence |
SMNIYLVLDG
252 SDSIGASNFT262 GAKKVLVNLI272 EKVASYGVKP282 RYGLVTYATY292 PKIWVKVSEA 302 DSSNADWVTK312 QLNEINYEDH322 KLKSGTNTKK332 ALQAVYSMMS342 WPGWNRTRHV 358 IILMTDGLHN368 MGGDPITVID378 EIRDLLYIGK388 DRKNPREDYL398 DVYVFGVGPL 408 VNQVNINALA418 SKKDNEQHVC428 KVKDMECLED438 VFYQMIDESQ448 SLSLCGMVWE 458 HRKGTDYHKQ468 PWQAKISVIR478 KGHESCMGAV490 VSEYFVLTAA500 HCFTVDDKEH 510 SIKVSVGGEK520 RDLEIEVVLF530 HPNYNINGKK540 EAGIPEFYDY550 DVALIKLKNK 560 LKYGQTIRPI570 CLPCTEGTTR580 ALRLPPTTTC590 QQQKEELLPA600 QDIKALFVSE 610 EEKKLTRKEV620 YIKNGDKKGS630 CERDAQYAPG640 YDKVKDISEV650 VTPRFLCTGG 660 VSPYADPNTC670 RGDSGGPLIV680 HKRSRFIQVG690 VISWGVVDVC700 KRQKQVPAHA 713 RDFHINLFQV723 LPWLKEKLQD733 EDLGFL
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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 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 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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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| Complement and coagulation cascades | hsa04610 | Affiliated Target |
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| Class: Organismal Systems => Immune system | Pathway Hierarchy | ||
| Degree | 4 | Degree centrality | 4.30E-04 | Betweenness centrality | 7.86E-06 |
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| Closeness centrality | 1.61E-01 | Radiality | 1.24E+01 | Clustering coefficient | 5.00E-01 |
| Neighborhood connectivity | 1.05E+01 | Topological coefficient | 3.09E-01 | Eccentricity | 14 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
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| 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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| KEGG Pathway | [+] 2 KEGG Pathways | + | ||||
| 1 | Complement and coagulation cascades | |||||
| 2 | Staphylococcus aureus infection | |||||
| NetPath Pathway | [+] 1 NetPath Pathways | + | ||||
| 1 | TGF_beta_Receptor Signaling Pathway | |||||
| Reactome | [+] 3 Reactome Pathways | + | ||||
| 1 | Alternative complement activation | |||||
| 2 | Activation of C3 and C5 | |||||
| 3 | Regulation of Complement cascade | |||||
| WikiPathways | [+] 3 WikiPathways | + | ||||
| 1 | Complement and Coagulation Cascades | |||||
| 2 | Human Complement System | |||||
| 3 | Complement cascade | |||||
| References | Top | |||||
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| REF 1 | FDA Approved Drug Products from FDA Official Website. 2023. Application Number: 218276 | |||||
| REF 2 | ClinicalTrials.gov (NCT03373461) Study of Safety and Efficacy of LNP023 in Patients With Kidney Disease Caused by Inflammation. U.S. National Institutes of Health. | |||||
| REF 3 | Clinical pipeline report, company report or official report of Roche | |||||
| REF 4 | Clinical pipeline report, company report or official report of Sanofi | |||||
| REF 5 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800010210) | |||||
| REF 6 | Complement Inhibitors in Clinical Trials for Glomerular Diseases. Front Immunol. 2019 Sep 27;10:2166. | |||||
| REF 7 | A soluble chimeric inhibitor of C3 and C5 convertases, complement activation blocker-2, prolongs graft survival in pig-to-rhesus monkey heart transplantation. Xenotransplantation. 2002 Mar;9(2):125-34. | |||||
| 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. (Target id: 2339). | |||||
| REF 9 | Structure-activity relationships for substrate-based inhibitors of human complement factor B. J Med Chem. 2009 Oct 8;52(19):6042-52. | |||||
| REF 10 | Structural analysis of engineered Bb fragment of complement factor B: insights into the activation mechanism of the alternative pathway C3-convertase. Mol Cell. 2004 Apr 9;14(1):17-28. | |||||
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