Target Information

Target General Infomation
Target ID
T87024
Former ID
TTDC00180
Target Name
Amyloid beta A4 protein
Gene Name
APP
Synonyms
ABPP; APPI; Alzheimer's disease amyloid protein; Amyloid beta precursor protein; Amyloid precursor protein; Beta-amyloid peptide; CVAP; Cerebral vascular amyloidpeptide; Gamma-Secretase; PN-II; PreA4; Protease nexin-II; Vascular beta-amyloid; APP
Target Type
Successful
Disease Alzheimer disease [ICD9: 331; ICD10: G30]
Age related macular degeneration [ICD9: 362.5; ICD10: H35.3]
Amyloidosis [ICD9: 277.3; ICD10: E85]
Brain injury [ICD10: S09.90]
Cerebral amyloid angiopathy [ICD10: I68.0]
Cancer [ICD9: 140-229; ICD10: C00-C96]
Diagnostic imaging [ICD9: 331; ICD10: G30, I73.9]
Glioma [ICD9: 191; ICD10: C71]
Geographic retinal atrophy; Macular degeneration [ICD9:362.5; ICD10: H35.3]
Mild cognitive impairment [ICD9: 331.83; ICD10: F06.7]
Mild to moderate alzheimer disease [ICD9: 331; ICD10: G30]
Neurological disease [ICD9: 338, 338.2, 410, 782.3,780; ICD10: I21, I22, R52, R52.1-R52.2, R60.9, G89]
Unspecified [ICD code not available]
Function
Essential subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral proteins such as Notch receptors and APP (beta-amyloid precursor protein). It probably representsa stabilizing cofactor for the presenilin homodimer that promotes the formation of a stable complex.
BioChemical Class
Peptidase
Target Validation
T87024
UniProt ID
P05067
Sequence
MLPGLALLLLAAWTARALEVPTDGNAGLLAEPQIAMFCGRLNMHMNVQNGKWDSDPSGTK
TCIDTKEGILQYCQEVYPELQITNVVEANQPVTIQNWCKRGRKQCKTHPHFVIPYRCLVG
EFVSDALLVPDKCKFLHQERMDVCETHLHWHTVAKETCSEKSTNLHDYGMLLPCGIDKFR
GVEFVCCPLAEESDNVDSADAEEDDSDVWWGGADTDYADGSEDKVVEVAEEEEVAEVEEE
EADDDEDDEDGDEVEEEAEEPYEEATERTTSIATTTTTTTESVEEVVREVCSEQAETGPC
RAMISRWYFDVTEGKCAPFFYGGCGGNRNNFDTEEYCMAVCGSAMSQSLLKTTQEPLARD
PVKLPTTAASTPDAVDKYLETPGDENEHAHFQKAKERLEAKHRERMSQVMREWEEAERQA
KNLPKADKKAVIQHFQEKVESLEQEAANERQQLVETHMARVEAMLNDRRRLALENYITAL
QAVPPRPRHVFNMLKKYVRAEQKDRQHTLKHFEHVRMVDPKKAAQIRSQVMTHLRVIYER
MNQSLSLLYNVPAVAEEIQDEVDELLQKEQNYSDDVLANMISEPRISYGNDALMPSLTET
KTTVELLPVNGEFSLDDLQPWHSFGADSVPANTENEVEPVDARPAADRGLTTRPGSGLTN
IKTEEISEVKMDAEFRHDSGYEVHHQKLVFFAEDVGSNKGAIIGLMVGGVVIATVIVITL
VMLKKKQYTSIHHGVVEVDAAVTPEERHLSKMQQNGYENPTYKFFEQMQN
Drugs and Mode of Action
Drug(s) Florbetapir F-18 Drug Info Approved Diagnostic imaging [1]
Bapineuzumab Drug Info Phase 3 Alzheimer disease [2], [3]
BIIB037 Drug Info Phase 3 Alzheimer disease [4]
Curcumin Drug Info Phase 3 Cancer [5], [6]
NI-101 Drug Info Phase 3 Alzheimer disease [4], [7]
Solanezumab Drug Info Phase 3 Alzheimer disease [8], [9]
Tramiprosate Drug Info Phase 3 Alzheimer disease [10]
CAD-106 Drug Info Phase 2/3 Alzheimer disease [11]
AN-1792 Drug Info Phase 2 Alzheimer disease [12]
BAN2401 Drug Info Phase 2 Alzheimer disease [13]
Crenezumab Drug Info Phase 2 Alzheimer disease [14], [15]
ELND005 Drug Info Phase 2 Mild to moderate alzheimer disease [16]
FRM-0962 Drug Info Phase 2 Alzheimer disease [17]
GSK933776 Drug Info Phase 2 Geographic retinal atrophy; Macular degeneration [18]
GSK933776A Drug Info Phase 2 Alzheimer disease [19]
NIC5-15 Drug Info Phase 2 Alzheimer disease [20]
Ponezumab Drug Info Phase 2 Alzheimer disease [21]
UB-311 Drug Info Phase 2 Alzheimer disease [22]
ACI-24 Drug Info Phase 1/2 Alzheimer disease [23]
11C-6-Me-BTA-1 Drug Info Phase 1 Alzheimer disease [24]
11C-AZD-2184 Drug Info Phase 1 Alzheimer disease [25]
AAB-003/PF-05236812 Drug Info Phase 1 Alzheimer disease [26]
AD-03 Drug Info Phase 1 Alzheimer disease [27]
Affitope AD-01 Drug Info Phase 1 Alzheimer disease [28]
ALZ-801 Drug Info Phase 1 Alzheimer disease [29]
Anti-N3pG-Abeta antibody Drug Info Phase 1 Alzheimer disease [30]
DWP-09031 Drug Info Phase 1 Alzheimer disease [31]
V-950 Drug Info Phase 1 Alzheimer disease [32]
AAB-002 Drug Info Phase 0 Alzheimer disease [33]
NN-818 Drug Info Preclinical Brain injury [34]
Pepticlere Drug Info Preclinical Alzheimer disease [35]
Affitope AD-02 Drug Info Discontinued in Phase 2 Alzheimer disease [36]
RN6G Drug Info Discontinued in Phase 2 Age related macular degeneration [37]
PF-05236812 Drug Info Discontinued in Phase 1 Alzheimer disease [38]
Inhibitor 1,6-bis(4'-aminophenyl)-hexa-1,3,5-triene Drug Info [39]
1,6-bis(4'-dimethylaminophenyl)-hexa-1,3,5-triene Drug Info [39]
1,6-Bis(4'-hydroxyphenyl)-hexa-1,3,5-triene Drug Info [39]
1,6-bis(4'-methylaminophenyl)-hexa-1,3,5-triene Drug Info [39]
1,6-bis(4'-nitrophenyl)-hexa-1,3,5-triene Drug Info [39]
2,5-bis(2-methoxyphenyl)thiophene Drug Info [40]
2,5-bis(4-Hydroxyphenyl)thiophene Drug Info [40]
2,5-bis(4-methoxyphenyl)thiophene Drug Info [40]
2,5-bis(4-nitrophenyl)thiophene Drug Info [40]
2-(4-(methylamino)phenyl)benzo[d]thiazol-6-ol Drug Info [39]
2-(4-nitrophenyl)-5-(4-methoxyphenyl)thiophene Drug Info [40]
4-(5-(4-(methylamino)phenyl)thiophen-2-yl)phenol Drug Info [40]
4-(5-(4-aminophenyl)thiophen-2-yl)benzenamine Drug Info [40]
4-(5-(4-aminophenyl)thiophen-2-yl)phenol Drug Info [40]
4-(5-(4-methoxyphenyl)thiophen-2-yl)benzenamine Drug Info [40]
4-(5-(4-methoxyphenyl)thiophen-2-yl)phenol Drug Info [40]
5-hydroxy-2-(4-aminophenyl)benzofuran Drug Info [41]
5-hydroxy-2-(4-dimethylaminophenyl)benzofuran Drug Info [41]
5-hydroxy-2-(4-methylaminophenyl)benzofuran Drug Info [41]
5-methoxy-2-(4-aminophenyl)benzofuran Drug Info [41]
5-methoxy-2-(4-dimethylaminophenyl)benzofuran Drug Info [41]
5-methoxy-2-(4-methylaminophenyl)benzofuran Drug Info [41]
6-iodo-4'-dimethyaminoflavone Drug Info [42]
6-iodo-4'-hydroxyflavone Drug Info [42]
6-iodo-4'-methoxyflavone Drug Info [42]
6-iodo-4'-methylaminoflavone Drug Info [42]
A-887755 Drug Info [43]
Abloid Drug Info [43]
ACI-636 Drug Info [43]
ALZ-801 Drug Info [44]
AN-1792 Drug Info [45]
ANA-1 Drug Info [43]
ANA-5 Drug Info [43]
Anticalin Drug Info [43]
ARC-069 Drug Info [43]
ARN-2966 Drug Info [43]
AZ4800 Drug Info [46]
Chrysamine -G Drug Info [47]
CT-003230 Drug Info [43]
Curcumin Drug Info [47]
DBT-1339 Drug Info [43]
DEHYDROZINGERONE Drug Info [47]
DWP-09031 Drug Info [43]
ELND-007 Drug Info [48]
Gamma secretase inhibitors Drug Info [43]
KMS-88009 Drug Info [43]
Methionine Sulfoxide Drug Info [49]
NIC5-15 Drug Info [50]
Pepticlere Drug Info [51]
PF-05236812 Drug Info [52]
RN6G Drug Info [53]
SB-13 Drug Info [39]
SEM-606 Drug Info [43]
SEN-1500 Drug Info [43]
SP-08 Drug Info [43]
SR-973 Drug Info [54]
Systebryl Drug Info [43]
Turmeric extracts Drug Info [43]
VK-11 Drug Info [43]
VK-12 Drug Info [43]
Modulator 11C-6-Me-BTA-1 Drug Info [55]
123I-DRM-106 Drug Info [43]
18F-AV-45 dimer Drug Info [43]
AAB-002 Drug Info [43]
AAB-003/PF-05236812 Drug Info [43]
AS-602704 Drug Info
BAN-2203 Drug Info [43]
BAN2401 Drug Info [56]
Beta amyloid lowering agents Drug Info [43]
BIIB037 Drug Info [52]
Crenezumab Drug Info [43]
EDN-OL1 Drug Info [43]
ELND005 Drug Info [57]
Florbetapir F-18 Drug Info [58]
FRM-0962 Drug Info [59]
Gamma-secretase modulators Drug Info [43]
GSK933776 Drug Info [60]
GSK933776A Drug Info [61]
NN-818 Drug Info [43]
PA-1637 Drug Info [43]
Solanezumab Drug Info [62]
TKP-1001 Drug Info [43]
UB-311 Drug Info [63]
Binder 11C-AZD-2184 Drug Info [64]
Agonist CD45RB Drug Info [43]
Antagonist Tramiprosate Drug Info [65]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway Notch signaling pathway
Alzheimer&#039
s disease
Reactome Nuclear signaling by ERBB4
Degradation of the extracellular matrix
Regulated proteolysis of p75NTR
NRIF signals cell death from the nucleus
Activated NOTCH1 Transmits Signal to the Nucleus
Constitutive Signaling by NOTCH1 PEST Domain Mutants
Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants
EPH-ephrin mediated repulsion of cells
WikiPathways Notch Signaling Pathway
Signaling by ERBB4
Signaling by NOTCH3
Signaling by NOTCH4
Signaling by NOTCH1
Signaling by NOTCH2
Notch Signaling Pathway
Alzheimers Disease
Signalling by NGF
References
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REF 4ClinicalTrials.gov (NCT02484547) 221AD302 Phase 3 Study of Aducanumab (BIIB037) in Early Alzheimer's Disease.
REF 5Nanocurcumin: a promising therapeutic advancement over native curcumin. Crit Rev Ther Drug Carrier Syst. 2013;30(4):331-68.
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REF 10ClinicalTrials.gov (NCT00314912) Open-Label Extension of the Phase III Study With Tramiprosate (3APS) in Patients With Mild to Moderate Alzheimer's Disease. U.S. National Institutes of Health.
REF 11ClinicalTrials.gov (NCT02565511) A Study of CAD106 and CNP520 Versus Placebo in Participants at Risk for the Onset of Clinical Symptoms of Alzheimer's Disease.
REF 12ClinicalTrials.gov (NCT00021723) Randomized Safety, Tolerability and Pilot Efficacy of AN-1792 in Alzheimer's Disease. U.S. National Institutes of Health.
REF 13ClinicalTrials.gov (NCT01767311) A Study to Evaluate Safety, Tolerability, and Efficacy of BAN2401 in Subjects With Early Alzheimer's Disease. U.S. National Institutes of Health.
REF 14ClinicalTrials.gov (NCT01343966) A Study to Evaluate the Efficacy and Safety of MABT5102A in Patients With Mild to Moderate Alzheimer's Disease (ABBY). U.S. National Institutes of Health.
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REF 16ClinicalTrials.gov (NCT01766336) A 36-Week Safety Extension Study of ELND005 as a Treatment for Agitation and Aggression in Alzheimer's Disease. U.S. National Institutes of Health.
REF 17Clinical pipeline report, company report or official report of Forum pharmaceuticals.
REF 18ClinicalTrials.gov (NCT01342926) Clinical Study to Investigate Safety and Efficacy of GSK933776 in Adult Patients With Geographic Atrophy Secondary to Age-related Macular Degeneration. U.S. National Institutes of Health.
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REF 20ClinicalTrials.gov (NCT01928420) A Single Site, Randomized, Double-blind, Placebo Controlled Trial of NIC5-15 in Subjects With Alzheimer's Disease. U.S. National Institutes of Health.
REF 21ClinicalTrials.gov (NCT01821118) Study Evaluating the Safety,Tolerability and Efficacy of PF-04360365 in Adults With Probable Cerebral Amyloid Angiopathy. U.S. National Institutes of Health.
REF 22ClinicalTrials.gov (NCT02551809) Evaluate the Safety, Tolerability, Immunogenicity and Efficacy of UB-311 in Mild Alzheimer's Disease (AD) Patients.
REF 23Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800031074)
REF 24List of drugs in development for neurodegenerative diseases: update October 2011. Neurodegener Dis. 2012;9(4):210-83.
REF 25ClinicalTrials.gov (NCT00838877) Positron Emission Tomography (PET) Study With [18F]AZD4694 and [11C]AZD2184, Candidate PET Ligands for A??Amyloid. U.S. National Institutes of Health.
REF 26ClinicalTrials.gov (NCT01369225) Open Label Extension Study Evaluating Safety and Tolerability of AAB-003 (PF-05236812) in Subject With Mild to Moderate Alzheimer's Disease. U.S. National Institutes of Health.
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REF 28ClinicalTrials.gov (NCT00495417) Tolerability and Safety of Subcutaneous Administration of Affitope AD01 in Mild to Moderate Alzheimer's Disease. U.S. National Institutes of Health.
REF 29Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800040203)
REF 30ClinicalTrials.gov (NCT01837641) A Study of LY3002813 in Participants With Alzheimer's Disease. U.S. National Institutes of Health.
REF 31ClinicalTrials.gov (NCT01522586) Clinical Trial to Investigate the Safety, Tolerability, and Pharmacokinetics of DWP09031. U.S. National Institutes of Health.
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REF 33Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800024936)
REF 34Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800020811)
REF 35Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800023984)
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REF 41J Med Chem. 2006 May 4;49(9):2725-30.Novel benzofuran derivatives for PET imaging of beta-amyloid plaques in Alzheimer's disease brains.
REF 42J Med Chem. 2005 Nov 17;48(23):7253-60.Radioiodinated flavones for in vivo imaging of beta-amyloid plaques in the brain.
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REF 44Oral Clinical Candidate ALZ-801 in Alzheon's pipeline. 2012.
REF 45Amyloid-beta peptide remnants in AN-1792-immunized Alzheimer's disease patients: a biochemical analysis. Am J Pathol. 2006 Sep;169(3):1048-63.
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