Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTFRCTK)

DTT Name CREB-binding protein (CREBBP)
Synonyms CREBbinding protein; CBP
Gene Name CREBBP
DTT Type
Clinical trial target
 [1]
BioChemical Class
Acyltransferase
UniProt ID
CBP_HUMAN
TTD ID
T03634
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
EC 2.3.1.48
Sequence
MAENLLDGPPNPKRAKLSSPGFSANDSTDFGSLFDLENDLPDELIPNGGELGLLNSGNLV
PDAASKHKQLSELLRGGSGSSINPGIGNVSASSPVQQGLGGQAQGQPNSANMASLSAMGK
SPLSQGDSSAPSLPKQAASTSGPTPAASQALNPQAQKQVGLATSSPATSQTGPGICMNAN
FNQTHPGLLNSNSGHSLINQASQGQAQVMNGSLGAAGRGRGAGMPYPTPAMQGASSSVLA
ETLTQVSPQMTGHAGLNTAQAGGMAKMGITGNTSPFGQPFSQAGGQPMGATGVNPQLASK
QSMVNSLPTFPTDIKNTSVTNVPNMSQMQTSVGIVPTQAIATGPTADPEKRKLIQQQLVL
LLHAHKCQRREQANGEVRACSLPHCRTMKNVLNHMTHCQAGKACQVAHCASSRQIISHWK
NCTRHDCPVCLPLKNASDKRNQQTILGSPASGIQNTIGSVGTGQQNATSLSNPNPIDPSS
MQRAYAALGLPYMNQPQTQLQPQVPGQQPAQPQTHQQMRTLNPLGNNPMNIPAGGITTDQ
QPPNLISESALPTSLGATNPLMNDGSNSGNIGTLSTIPTAAPPSSTGVRKGWHEHVTQDL
RSHLVHKLVQAIFPTPDPAALKDRRMENLVAYAKKVEGDMYESANSRDEYYHLLAEKIYK
IQKELEEKRRSRLHKQGILGNQPALPAPGAQPPVIPQAQPVRPPNGPLSLPVNRMQVSQG
MNSFNPMSLGNVQLPQAPMGPRAASPMNHSVQMNSMGSVPGMAISPSRMPQPPNMMGAHT
NNMMAQAPAQSQFLPQNQFPSSSGAMSVGMGQPPAQTGVSQGQVPGAALPNPLNMLGPQA
SQLPCPPVTQSPLHPTPPPASTAAGMPSLQHTTPPGMTPPQPAAPTQPSTPVSSSGQTPT
PTPGSVPSATQTQSTPTVQAAAQAQVTPQPQTPVQPPSVATPQSSQQQPTPVHAQPPGTP
LSQAAASIDNRVPTPSSVASAETNSQQPGPDVPVLEMKTETQAEDTEPDPGESKGEPRSE
MMEEDLQGASQVKEETDIAEQKSEPMEVDEKKPEVKVEVKEEEESSSNGTASQSTSPSQP
RKKIFKPEELRQALMPTLEALYRQDPESLPFRQPVDPQLLGIPDYFDIVKNPMDLSTIKR
KLDTGQYQEPWQYVDDVWLMFNNAWLYNRKTSRVYKFCSKLAEVFEQEIDPVMQSLGYCC
GRKYEFSPQTLCCYGKQLCTIPRDAAYYSYQNRYHFCEKCFTEIQGENVTLGDDPSQPQT
TISKDQFEKKKNDTLDPEPFVDCKECGRKMHQICVLHYDIIWPSGFVCDNCLKKTGRPRK
ENKFSAKRLQTTRLGNHLEDRVNKFLRRQNHPEAGEVFVRVVASSDKTVEVKPGMKSRFV
DSGEMSESFPYRTKALFAFEEIDGVDVCFFGMHVQEYGSDCPPPNTRRVYISYLDSIHFF
RPRCLRTAVYHEILIGYLEYVKKLGYVTGHIWACPPSEGDDYIFHCHPPDQKIPKPKRLQ
EWYKKMLDKAFAERIIHDYKDIFKQATEDRLTSAKELPYFEGDFWPNVLEESIKELEQEE
EERKKEESTAASETTEGSQGDSKNAKKKNNKKTNKNKSSISRANKKKPSMPNVSNDLSQK
LYATMEKHKEVFFVIHLHAGPVINTLPPIVDPDPLLSCDLMDGRDAFLTLARDKHWEFSS
LRRSKWSTLCMLVELHTQGQDRFVYTCNECKHHVETRWHCTVCEDYDLCINCYNTKSHAH
KMVKWGLGLDDEGSSQGEPQSKSPQESRRLSIQRCIQSLVHACQCRNANCSLPSCQKMKR
VVQHTKGCKRKTNGGCPVCKQLIALCCYHAKHCQENKCPVPFCLNIKHKLRQQQIQHRLQ
QAQLMRRRMATMNTRNVPQQSLPSPTSAPPGTPTQQPSTPQTPQPPAQPQPSPVSMSPAG
FPSVARTQPPTTVSTGKPTSQVPAPPPPAQPPPAAVEAARQIEREAQQQQHLYRVNINNS
MPPGRTGMGTPGSQMAPVSLNVPRPNQVSGPVMPSMPPGQWQQAPLPQQQPMPGLPRPVI
SMQAQAAVAGPRMPSVQPPRSISPSALQDLLRTLKSPSSPQQQQQVLNILKSNPQLMAAF
IKQRTAKYVANQPGMQPQPGLQSQPGMQPQPGMHQQPSLQNLNAMQAGVPRPGVPPQQQA
MGGLNPQGQALNIMNPGHNPNMASMNPQYREMLRRQLLQQQQQQQQQQQQQQQQQQGSAG
MAGGMAGHGQFQQPQGPGGYPPAMQQQQRMQQHLPLQGSSMGQMAAQMGQLGQMGQPGLG
ADSTPNIQQALQQRILQQQQMKQQIGSPGQPNPMSPQQHMLSGQPQASHLPGQQIATSLS
NQVRSPAPVQSPRPQSQPPHSSPSPRIQPQPSPHHVSPQTGSPHPGLAVTMASSIDQGHL
GNPEQSAMLPQLNTPSRSALSSELSLVGDTTGDTLEKFVEGL
Function
Acetylates non-histone proteins, like NCOA3 and FOXO1. Binds specifically to phosphorylated CREB and enhances its transcriptional activity toward cAMP-responsive genes. Acts as a coactivator of ALX1. Acts as a circadian transcriptional coactivator which enhances the activity of the circadian transcriptional activators: NPAS2-ARNTL/BMAL1 and CLOCK-ARNTL/BMAL1 heterodimers. Acetylates PCNA; acetylation promotes removal of chromatin-bound PCNA and its degradation during nucleotide excision repair (NER). Functions as a transcriptional coactivator for SMAD4 in the TGF-beta signaling pathway. Acetylates histones, giving a specific tag for transcriptional activation.
KEGG Pathway
cAMP signaling pathway (hsa04024 )
HIF-1 signaling pathway (hsa04066 )
FoxO signaling pathway (hsa04068 )
Cell cycle (hsa04110 )
Wnt signaling pathway (hsa04310 )
Notch signaling pathway (hsa04330 )
TGF-beta signaling pathway (hsa04350 )
Adherens junction (hsa04520 )
Jak-STAT signaling pathway (hsa04630 )
Long-term potentiation (hsa04720 )
Melanogenesis (hsa04916 )
Thyroid hormone signaling pathway (hsa04919 )
Glucagon signaling pathway (hsa04922 )
Huntington's disease (hsa05016 )
Tuberculosis (hsa05152 )
Hepatitis B (hsa05161 )
Influenza A (hsa05164 )
HTLV-I infection (hsa05166 )
Herpes simplex infection (hsa05168 )
Epstein-Barr virus infection (hsa05169 )
Pathways in cancer (hsa05200 )
Viral carcinogenesis (hsa05203 )
MicroRNAs in cancer (hsa05206 )
Renal cell carcinoma (hsa05211 )
Prostate cancer (hsa05215 )
Reactome Pathway
RORA activates gene expression (R-HSA-1368082 )
BMAL1 (R-HSA-1368108 )
Pre-NOTCH Transcription and Translation (R-HSA-1912408 )
PPARA activates gene expression (R-HSA-1989781 )
Formation of the beta-catenin (R-HSA-201722 )
YAP1- and WWTR1 (TAZ)-stimulated gene expression (R-HSA-2032785 )
NOTCH1 Intracellular Domain Regulates Transcription (R-HSA-2122947 )
Transcriptional activation of mitochondrial biogenesis (R-HSA-2151201 )
Activation of gene expression by SREBF (SREBP) (R-HSA-2426168 )
Constitutive Signaling by NOTCH1 PEST Domain Mutants (R-HSA-2644606 )
Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants (R-HSA-2894862 )
LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production (R-HSA-3134973 )
HATs acetylate histones (R-HSA-3214847 )
Attenuation phase (R-HSA-3371568 )
Notch-HLH transcription pathway (R-HSA-350054 )
Transcriptional regulation of white adipocyte differentiation (R-HSA-381340 )
Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha) (R-HSA-400206 )
Circadian Clock (R-HSA-400253 )
CD209 (DC-SIGN) signaling (R-HSA-5621575 )
TRAF3-dependent IRF activation pathway (R-HSA-918233 )
TRAF6 mediated IRF7 activation (R-HSA-933541 )
Factors involved in megakaryocyte development and platelet production (R-HSA-983231 )
Regulation of gene expression by Hypoxia-inducible Factor (R-HSA-1234158 )

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DTT
4 Clinical Trial Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
C 82 DMEWXFK Scleroderma 4A42 Phase 1/2 [2]
CCS1477 DM9UZM1 Solid tumour/cancer 2A00-2F9Z Phase 1/2 [3]
PRI-724 DM0HTEF Acute myeloid leukaemia 2A60 Phase 1/2 [1]
FT-7051 DMCK3OI Prostate cancer 2C82.0 Phase 1 [4]
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1 Patented Agent(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Pyrrolo-pyrrolone derivative 6 DMBW208 N. A. N. A. Patented [5]
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3 Investigative Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
I-CBP112 DMQX3W6 Discovery agent N.A. Investigative [6]
ischemin DMM2I9G Discovery agent N.A. Investigative [7]
SGC-CBP30 DMTLRGZ Discovery agent N.A. Investigative [8]
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References

1 Inhibition of Wnt/beta-catenin/CREB binding protein (CBP) signaling reverses pulmonary fibrosis. Proc Natl Acad Sci U S A. 2010 Aug 10;107(32):14309-14.
2 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
3 Targeting the p300/CBP Axis in Lethal Prostate Cancer. Cancer Discov. 2021 May;11(5):1118-1137.
4 Clinical pipeline report, company report or official report of FORMA Therapeutics.
5 BET inhibitors in cancer therapeutics: a patent review.Expert Opin Ther Pat. 2016;26(4):505-22.
6 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: 2734).
7 A small molecule binding to the coactivator CREB-binding protein blocks apoptosis in cardiomyocytes. Chem Biol. 2011 Apr 22;18(4):531-41.
8 Bromodomains and their pharmacological inhibitors. ChemMedChem. 2014 Mar;9(3):438-64.