Target Information
| Target General Information | Top | |||||
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| Target ID |
T83369
(Former ID: TTDC00078)
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| Target Name |
Coagulation factor IX (F9)
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| Synonyms |
Plasma thromboplastin component; PTC protein; Factor IX; Christmas factor
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| Gene Name |
F9
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 2 Target-related Diseases | + | ||||
| 1 | Bleeding disorder [ICD-11: GA20-GA21] | |||||
| 2 | Coagulation defect [ICD-11: 3B10] | |||||
| Function |
Factor IX is a vitamin K-dependent plasma protein that participates in the intrinsic pathway of blood coagulation by converting factor X to its active form in the presence of Ca(2+) ions, phospholipids, and factor VIIIa.
Click to Show/Hide
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| BioChemical Class |
Peptidase
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| UniProt ID | ||||||
| EC Number |
EC 3.4.21.22
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| Sequence |
MQRVNMIMAESPGLITICLLGYLLSAECTVFLDHENANKILNRPKRYNSGKLEEFVQGNL
ERECMEEKCSFEEAREVFENTERTTEFWKQYVDGDQCESNPCLNGGSCKDDINSYECWCP FGFEGKNCELDVTCNIKNGRCEQFCKNSADNKVVCSCTEGYRLAENQKSCEPAVPFPCGR VSVSQTSKLTRAETVFPDVDYVNSTEAETILDNITQSTQSFNDFTRVVGGEDAKPGQFPW QVVLNGKVDAFCGGSIVNEKWIVTAAHCVETGVKITVVAGEHNIEETEHTEQKRNVIRII PHHNYNAAINKYNHDIALLELDEPLVLNSYVTPICIADKEYTNIFLKFGSGYVSGWGRVF HKGRSALVLQYLRVPLVDRATCLRSTKFTIYNNMFCAGFHEGGRDSCQGDSGGPHVTEVE GTSFLTGIISWGEECAMKGKYGIYTKVSRYVNWIKEKTKLT Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| Drugs and Modes of Action | Top | |||||
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| Approved Drug(s) | [+] 2 Approved Drugs | + | ||||
| 1 | Emicizumab | Drug Info | Approved | Factor VIII deficiency | [2] | |
| 2 | Recombinant Factor IX | Drug Info | Approved | Bleeding disorder | [3] | |
| Clinical Trial Drug(s) | [+] 9 Clinical Trial Drugs | + | ||||
| 1 | AMT-061 | Drug Info | Phase 3 | Haemophilia B | [4] | |
| 2 | CSL-654 | Drug Info | Phase 3 | Factor IX deficiency | [5] | |
| 3 | Fidanacogene elaparvovec | Drug Info | Phase 3 | Haemophilia B | [6] | |
| 4 | RG6013 | Drug Info | Phase 3 | Haemophilia A | [7] | |
| 5 | TTP889 | Drug Info | Phase 2 | Blood forming organ disorder | [8] | |
| 6 | AMT-060 | Drug Info | Phase 1/2 | Factor IX deficiency | [9] | |
| 7 | SB-FIX | Drug Info | Phase 1/2 | Haemophilia B | [10] | |
| 8 | AAV2-hFIX16 | Drug Info | Phase 1 | Factor IX deficiency | [11] | |
| 9 | N9-GP | Drug Info | Phase 1 | Factor IX deficiency | [12] | |
| Discontinued Drug(s) | [+] 4 Discontinued Drugs | + | ||||
| 1 | RB-006 | Drug Info | Discontinued in Phase 3 | Vascular disease | [13] | |
| 2 | Trenonacog alfa | Drug Info | Discontinued in Phase 3 | Discovery agent | [14] | |
| 3 | SB 249417 | Drug Info | Discontinued in Phase 1 | Sepsis | [15] | |
| 4 | Draculin | Drug Info | Terminated | Thrombosis | [16] | |
| Mode of Action | [+] 3 Modes of Action | + | ||||
| Modulator | [+] 13 Modulator drugs | + | ||||
| 1 | Emicizumab | Drug Info | [2] | |||
| 2 | Recombinant Factor IX | Drug Info | [1] | |||
| 3 | CSL-654 | Drug Info | [18] | |||
| 4 | AMT-060 | Drug Info | [22] | |||
| 5 | AAV2-hFIX16 | Drug Info | [23] | |||
| 6 | N9-GP | Drug Info | [24] | |||
| 7 | Trenonacog alfa | Drug Info | [14] | |||
| 8 | Draculin | Drug Info | [27] | |||
| 9 | BNP-FIX | Drug Info | [29] | |||
| 10 | F-9TG | Drug Info | [29] | |||
| 11 | Factor IX-XTEN | Drug Info | [29] | |||
| 12 | MG-1104 | Drug Info | [29] | |||
| 13 | MOD-3012 | Drug Info | [29] | |||
| Replacement | [+] 2 Replacement drugs | + | ||||
| 1 | Fidanacogene elaparvovec | Drug Info | [19] | |||
| 2 | SB-FIX | Drug Info | [10] | |||
| Inhibitor | [+] 10 Inhibitor drugs | + | ||||
| 1 | TTP889 | Drug Info | [8], [21] | |||
| 2 | RB-006 | Drug Info | [25] | |||
| 3 | 4-Benzyloxybenzo[b]thiophene-2-carboxamidine | Drug Info | [28] | |||
| 4 | 4-iodobenzo[b]thiophene 2-carboxamidine | Drug Info | [28] | |||
| 5 | 4-Phenyl-benzo[b]thiophene-2-carboxamidine | Drug Info | [28] | |||
| 6 | 5-Benzyloxy-benzo[b]thiophene-2-carboxamidine | Drug Info | [28] | |||
| 7 | 6-Benzyloxybenzo[b]thiophene-2-carboxamidine | Drug Info | [28] | |||
| 8 | Gamma-Carboxy-Glutamic Acid | Drug Info | [30] | |||
| 9 | PMID20121197C57 | Drug Info | [31] | |||
| 10 | RAZAXABAN | Drug Info | [32] | |||
| 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 | ||
| Target Poor or Non Binders | Top | |||||
|---|---|---|---|---|---|---|
| Target Poor or Non Binders | ||||||
| Target Regulators | Top | |||||
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| Target-regulating Transcription Factors | ||||||
| Target Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 1 KEGG Pathways | + | ||||
| 1 | Complement and coagulation cascades | |||||
| Panther Pathway | [+] 1 Panther Pathways | + | ||||
| 1 | Blood coagulation | |||||
| Pathwhiz Pathway | [+] 1 Pathwhiz Pathways | + | ||||
| 1 | Coagulation | |||||
| Reactome | [+] 5 Reactome Pathways | + | ||||
| 1 | Extrinsic Pathway of Fibrin Clot Formation | |||||
| 2 | Intrinsic Pathway of Fibrin Clot Formation | |||||
| 3 | Gamma-carboxylation of protein precursors | |||||
| 4 | Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus | |||||
| 5 | Removal of aminoterminal propeptides from gamma-carboxylated proteins | |||||
| WikiPathways | [+] 4 WikiPathways | + | ||||
| 1 | Complement and Coagulation Cascades | |||||
| 2 | PTM: gamma carboxylation, hypusine formation and arylsulfatase activation | |||||
| 3 | Blood Clotting Cascade | |||||
| 4 | Formation of Fibrin Clot (Clotting Cascade) | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | BAX326 (RIXUBIS): a novel recombinant factor IX for the control and prevention of bleeding episodes in adults and children with hemophilia B. Ther Adv Hematol. 2014 Oct;5(5):168-80. | |||||
| REF 2 | 2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85. | |||||
| REF 3 | DAILYMED.nlm.nih.gov:IXINITY- coagulation factor ix (recombinant) | |||||
| REF 4 | ClinicalTrials.gov (NCT03569891) HOPE-B: Trial of AMT-061 in Severe or Moderately Severe Hemophilia B Patients. U.S. National Institutes of Health. | |||||
| REF 5 | ClinicalTrials.gov (NCT02053792) A Safety and Efficacy Extension Study of a Recombinant Fusion Protein Linking Coagulation Factor IX With Albumin (rIX-FP) in Patients With Hemophilia B. U.S. NationalInstitutes of Health. | |||||
| REF 6 | ClinicalTrials.gov (NCT03861273) A Study to Evaluate the Efficacy and Safety of Factor IX Gene Therapy With PF-06838435 in Adult Males With Moderately Severe to Severe Hemophilia B (BENEGENE-2). U.S. National Institutes of Health. | |||||
| REF 7 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 8 | Partial factor IXa inhibition with TTP889 for prevention of venous thromboembolism: an exploratory study. J Thromb Haemost. 2008 Mar;6(3):457-63. | |||||
| REF 9 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800026919) | |||||
| REF 10 | ClinicalTrials.gov (NCT02695160) Ascending Dose Study of Genome Editing by Zinc Finger Nuclease Therapeutic SB-FIX in Subjects With Severe Hemophilia B. U.S. National Institutes of Health. | |||||
| REF 11 | ClinicalTrials.gov (NCT00515710) LTFU for Gene Transfer Subjects With Hemophilia B. U.S. National Institutes of Health. | |||||
| REF 12 | ClinicalTrials.gov (NCT01395810) Safety and Efficacy of NNC-0156-0000-0009 After Long-Term Exposure in Patients With Haemophilia B: An Extension to Trials NN7999-3747 and NN7999-3773. U.S. National Institutes of Health. | |||||
| REF 13 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800019932) | |||||
| REF 14 | Pharmacokinetic properties of IB1001, an investigational recombinant factor IX, in patients with haemophilia B: repeat pharmacokinetic evaluation and sialylation analysis.Haemophilia.2012 Nov;18(6):881-7. | |||||
| REF 15 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800010912) | |||||
| REF 16 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004668) | |||||
| REF 17 | Clinical pipeline report, company report or official report of uniQure. | |||||
| REF 18 | Safety and pharmacokinetics of a novel recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in hemophilia B patients. Blood. 2012 September 20; 120(12): 2405-2411. | |||||
| REF 19 | Factor IX assay discrepancies in the setting of liver gene therapy using a hyperfunctional variant factor IX-Padua. J Thromb Haemost. 2021 May;19(5):1212-1218. | |||||
| REF 20 | Anti-factor IXa/X bispecific antibody (ACE910): hemostatic potency against ongoing bleeds in a hemophilia A model and the possibility of routine supplementation. J Thromb Haemost. 2014 Feb;12(2):206-13. | |||||
| REF 21 | Oral anticoagulants in development: focus on thromboprophylaxis in patients undergoing orthopaedic surgery. Drugs. 2006;66(11):1411-29. | |||||
| REF 22 | Phase I/II clinical trial of AMT-060 for treating hemophilia B. uniQure N.V. | |||||
| REF 23 | Assessing the potential for AAV vector genotoxicity in a murine model. Correction in: Blood. 2011 June 16; 117(24): 6739. | |||||
| REF 24 | Enhanced pharmacokinetic properties of a glycoPEGylated recombinant factor IX: a first human dose trial in patients with hemophilia B. Blood. 2011 Sep 8;118(10):2695-701. | |||||
| REF 25 | In-vitro evaluation of anti-factor IXa aptamer on thrombin generation, clotting time, and viscoelastometry. Thromb Haemost. 2009 May;101(5):827-33. | |||||
| REF 26 | Pharmacokinetic and pharmacodynamic modeling of humanized anti-factor IX antibody (SB 249417) in humans. Clin Pharmacol Ther. 2002 Apr;71(4):235-45. | |||||
| REF 27 | Expression of biological activity of draculin, the anticoagulant factor from vampire bat saliva, is strictly dependent on the appropriate glycosylation of the native molecule. Biochim Biophys Acta. 1998 Oct 23;1425(2):291-9. | |||||
| REF 28 | Studies of benzothiophene template as potent factor IXa (FIXa) inhibitors in thrombosis. J Med Chem. 2010 Feb 25;53(4):1465-72. | |||||
| REF 29 | 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: 2364). | |||||
| REF 30 | How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | |||||
| REF 31 | Structure based drug design: development of potent and selective factor IXa (FIXa) inhibitors. J Med Chem. 2010 Feb 25;53(4):1473-82. | |||||
| REF 32 | Aminobenzisoxazoles with biaryl P4 moieties as potent, selective, and orally bioavailable factor Xa inhibitors. Bioorg Med Chem Lett. 2006 Apr 1;16(7):1795-8. | |||||
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