Target Information
Target General Information | Top | |||||
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Target ID |
T75888
(Former ID: TTDS00433)
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Target Name |
Carnitine O-palmitoyltransferase I (CPT1B)
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Synonyms |
KIAA1670; Carnitine palmitoyltransferase I-like protein; Carnitine palmitoyltransferase I; Carnitine palmitoyltransferase 1B; Carnitine palmitoyl-transferase I; Carnitine o-palmitoyltransferase-1; Carnitine O-palmitoyltransferase I, muscle isoform; Carnitine O-palmitoyltransferase 1, muscle isoform; CPTI-M; CPTI-L; CPT1-M; CPT-1; CPT I; CPT
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Gene Name |
CPT1B
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Target Type |
Successful target
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[1] | ||||
Disease | [+] 3 Target-related Diseases | + | ||||
1 | Angina pectoris [ICD-11: BA40] | |||||
2 | Mild neurocognitive disorder [ICD-11: 6D71] | |||||
3 | Nutritional deficiency [ICD-11: 5B50-5B71] | |||||
Function |
mitochondrial outer membrane, mitochondrion, carnitine O-palmitoyltransferase activity, carnitine metabolic process, carnitine shuttle, fatty acid beta-oxidation, long-chain fatty acid transport.
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BioChemical Class |
Acyltransferase
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UniProt ID | ||||||
EC Number |
EC 2.3.1.21
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Sequence |
MAEAHQAVAFQFTVTPDGVDFRLSREALKHVYLSGINSWKKRLIRIKNGILRGVYPGSPT
SWLVVIMATVGSSFCNVDISLGLVSCIQRCLPQGCGPYQTPQTRALLSMAIFSTGVWVTG IFFFRQTLKLLLCYHGWMFEMHGKTSNLTRIWAMCIRLLSSRHPMLYSFQTSLPKLPVPR VSATIQRYLESVRPLLDDEEYYRMELLAKEFQDKTAPRLQKYLVLKSWWASNYVSDWWEE YIYLRGRSPLMVNSNYYVMDLVLIKNTDVQAARLGNIIHAMIMYRRKLDREEIKPVMALG IVPMCSYQMERMFNTTRIPGKDTDVLQHLSDSRHVAVYHKGRFFKLWLYEGARLLKPQDL EMQFQRILDDPSPPQPGEEKLAALTAGGRVEWAQARQAFFSSGKNKAALEAIERAAFFVA LDEESYSYDPEDEASLSLYGKALLHGNCYNRWFDKSFTLISFKNGQLGLNAEHAWADAPI IGHLWEFVLGTDSFHLGYTETGHCLGKPNPALAPPTRLQWDIPKQCQAVIESSYQVAKAL ADDVELYCFQFLPFGKGLIKKCRTSPDAFVQIALQLAHFRDRGKFCLTYEASMTRMFREG RTETVRSCTSESTAFVQAMMEGSHTKADLRDLFQKAAKKHQNMYRLAMTGAGIDRHLFCL YLVSKYLGVSSPFLAEVLSEPWRLSTSQIPQSQIRMFDPEQHPNHLGAGGGFGPVADDGY GVSYMIAGENTIFFHISSKFSSSETNAQRFGNHIRKALLDIADLFQVPKAYS Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
HIT2.0 ID | T51U9M |
Drugs and Modes of Action | Top | |||||
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Approved Drug(s) | [+] 2 Approved Drugs | + | ||||
1 | Levacecarnine hci | Drug Info | Approved | Nutritional deficiency | [2], [3], [4] | |
2 | Perhexiline | Drug Info | Approved | Angina pectoris | [1] | |
Discontinued Drug(s) | [+] 3 Discontinued Drugs | + | ||||
1 | SDZ-CPI-975 | Drug Info | Discontinued in Phase 1 | Diabetic complication | [5] | |
2 | DB-200 | Drug Info | Terminated | Psoriasis vulgaris | [6] | |
3 | Etomoxir | Drug Info | Terminated | Heart failure | [7] | |
Mode of Action | [+] 3 Modes of Action | + | ||||
Activator | [+] 2 Activator drugs | + | ||||
1 | Levacecarnine hci | Drug Info | [8] | |||
2 | C75 | Drug Info | [11] | |||
Inhibitor | [+] 3 Inhibitor drugs | + | ||||
1 | Perhexiline | Drug Info | [1] | |||
2 | SDZ-CPI-975 | Drug Info | [9] | |||
3 | DB-200 | Drug Info | [10] | |||
Modulator | [+] 1 Modulator drugs | + | ||||
1 | Etomoxir | Drug Info | [7] |
Cell-based Target Expression Variations | Top | |||||
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Cell-based Target Expression Variations |
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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Fatty acid degradation | hsa00071 | Affiliated Target |
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Class: Metabolism => Lipid metabolism | Pathway Hierarchy | ||
PPAR signaling pathway | hsa03320 | Affiliated Target |
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Class: Organismal Systems => Endocrine system | Pathway Hierarchy | ||
AMPK signaling pathway | hsa04152 | Affiliated Target |
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Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
Thermogenesis | hsa04714 | Affiliated Target |
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Class: Organismal Systems => Environmental adaptation | Pathway Hierarchy | ||
Adipocytokine signaling pathway | hsa04920 | Affiliated Target |
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Class: Organismal Systems => Endocrine system | Pathway Hierarchy | ||
Glucagon signaling pathway | hsa04922 | Affiliated Target |
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Class: Organismal Systems => Endocrine system | Pathway Hierarchy | ||
Click to Show/Hide the Information of Affiliated Human Pathways |
Degree | 1 | Degree centrality | 1.07E-04 | Betweenness centrality | 0.00E+00 |
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Closeness centrality | 1.47E-01 | Radiality | 1.18E+01 | Clustering coefficient | 0.00E+00 |
Neighborhood connectivity | 5.00E+00 | Topological coefficient | 1.00E+00 | Eccentricity | 13 |
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 Transcription Factors |
Target Affiliated Biological Pathways | Top | |||||
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KEGG Pathway | [+] 6 KEGG Pathways | + | ||||
1 | Fatty acid degradation | |||||
2 | Fatty acid metabolism | |||||
3 | PPAR signaling pathway | |||||
4 | AMPK signaling pathway | |||||
5 | Adipocytokine signaling pathway | |||||
6 | Glucagon signaling pathway | |||||
Pathwhiz Pathway | [+] 1 Pathwhiz Pathways | + | ||||
1 | Fatty acid Metabolism | |||||
Reactome | [+] 3 Reactome Pathways | + | ||||
1 | RORA activates gene expression | |||||
2 | PPARA activates gene expression | |||||
3 | Import of palmitoyl-CoA into the mitochondrial matrix | |||||
WikiPathways | [+] 8 WikiPathways | + | ||||
1 | SIDS Susceptibility Pathways | |||||
2 | Mitochondrial LC-Fatty Acid Beta-Oxidation | |||||
3 | Nuclear Receptors Meta-Pathway | |||||
4 | PPAR Alpha Pathway | |||||
5 | Regulation of Lipid Metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha) | |||||
6 | Circadian Clock | |||||
7 | Fatty Acid Beta Oxidation | |||||
8 | AMPK Signaling |
Target-Related Models and Studies | Top | |||||
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Target Validation |
References | Top | |||||
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REF 1 | Perhexiline. Cardiovasc Drug Rev. 2007 Spring;25(1):76-97. | |||||
REF 2 | 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: 4780). | |||||
REF 3 | Emerging drugs in peripheral arterial disease. Expert Opin Emerg Drugs. 2006 Mar;11(1):75-90. | |||||
REF 4 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
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 800005522) | |||||
REF 6 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800026687) | |||||
REF 7 | Etomoxir, a carnitine palmitoyltransferase I inhibitor, protects hearts from fatty acid-induced ischemic injury independent of changes in long chain acylcarnitine. Circ Res. 1988 Dec;63(6):1036-43. | |||||
REF 8 | Central ghrelin regulates peripheral lipid metabolism in a growth hormone-independent fashion. Endocrinology. 2009 Oct;150(10):4562-74. | |||||
REF 9 | Hypoglycemic effects of a novel fatty acid oxidation inhibitor in rats and monkeys. Am J Physiol. 1998 Feb;274(2 Pt 2):R524-8. | |||||
REF 10 | Comparison of the effects of carnitine palmitoyltransferase-1 and -2 inhibitors on rat heart hypertrophy. Cardioscience. 1994 Sep;5(3):193-7. | |||||
REF 11 | C75 increases peripheral energy utilization and fatty acid oxidation in diet-induced obesity. Proc Natl Acad Sci U S A. 2002 Jul 9;99(14):9498-502. |
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