Identification
- Summary
Cambinol is an investigational histone deacetylase inhibitor that may have future use in cancer treatment.
- Generic Name
- Cambinol
- DrugBank Accession Number
- DB15493
- Background
Cambinol is a beta-naphtol derivative that inhibits NAD-dependant deacetylases to reduce cell survival under stress. This activity is currently being investigated for its use as a cancer treatment.
- Type
- Small Molecule
- Groups
- Experimental
- Structure
Structure for Cambinol (DB15493)
- Weight
- Average: 360.43
Monoisotopic: 360.093248937 - Chemical Formula
- C21H16N2O2S
- Synonyms
- Not Available
- External IDs
- HY-100732
Pharmacology
- Indication
Not Available
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Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Not Available
- Mechanism of action
Cambinol inhibits the NAD-dependant deacetylases SIRT1 and SIRT2, members of a protein family known as sirtuins.1,2
Inhibiting SIRT1 and SIRT2 while cells are under stress increases acetylation of p53, Ku70, and Foxo3a.1,2 This inhibition sensitizes cells to the action of drugs like etoposide and paclitaxel, not just other drugs that damage DNA.1 Although the mechanism of this sensitizing is not defined, it is not dependent on p53, Ku70, or Foxo3a.1 The independent mechanism suggests the existence of more molecular targets.1
Cambinol is noncompetitive against NAD and competitive against H-4 peptide, substrates of SIRT2.1 Inhibiting SIRT2 increases the acetylation of tubulin.1
Cambinol also increases the acetylation of BCL6, a protein necessary for oncogenesis.1
Cambinol is also a weak inhibitor of SIRT5.2
Target Actions Organism ANAD-dependent protein deacetylase sirtuin-1 inhibitorHumans ANAD-dependent protein deacetylase sirtuin-2 inhibitorHumans NNAD-dependent protein deacylase sirtuin-5, mitochondrial inhibitorHumans - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Not Available
- Half-life
Not Available
- Clearance
Not Available
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.Not Available
- Food Interactions
- Not Available
Categories
- Drug Categories
- Classification
- Not classified
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 8S2PHY4FNC
- CAS number
- 14513-15-6
- InChI Key
- RVNSQVIUFZVNAU-UHFFFAOYSA-N
- InChI
- InChI=1S/C21H16N2O2S/c24-18-11-10-13-6-4-5-9-15(13)16(18)12-17-19(14-7-2-1-3-8-14)22-21(26)23-20(17)25/h1-11,24H,12H2,(H2,22,23,25,26)
- IUPAC Name
- 5-[(2-hydroxynaphthalen-1-yl)methyl]-6-phenyl-2-sulfanylidene-1,2,3,4-tetrahydropyrimidin-4-one
- SMILES
- OC1=C(CC2=C(NC(=S)NC2=O)C2=CC=CC=C2)C2=CC=CC=C2C=C1
References
- General References
- Heltweg B, Gatbonton T, Schuler AD, Posakony J, Li H, Goehle S, Kollipara R, Depinho RA, Gu Y, Simon JA, Bedalov A: Antitumor activity of a small-molecule inhibitor of human silent information regulator 2 enzymes. Cancer Res. 2006 Apr 15;66(8):4368-77. doi: 10.1158/0008-5472.CAN-05-3617. [Article]
- Med Chem Express: Cambinol Product Data Sheet [Link]
- External Links
- ChemSpider
- 2497101
- BindingDB
- 29040
- ChEMBL
- CHEMBL491960
- ZINC
- ZINC000007996283
Clinical Trials
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Not Available
- Experimental Properties
Property Value Source water solubility <0.1mg/mL Med Chem Express: Cambinol Product Data Sheet - Predicted Properties
Property Value Source Water Solubility 0.00319 mg/mL ALOGPS logP 4.01 ALOGPS logP 3.99 Chemaxon logS -5 ALOGPS pKa (Strongest Acidic) 7.96 Chemaxon pKa (Strongest Basic) -2.8 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 2 Chemaxon Hydrogen Donor Count 3 Chemaxon Polar Surface Area 61.36 Å2 Chemaxon Rotatable Bond Count 3 Chemaxon Refractivity 107.13 m3·mol-1 Chemaxon Polarizability 37.57 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-03di-0039000000-bf4d4e489603f5c01417 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-056r-0009000000-762507e245883c16ad24 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0a4i-3059000000-a38274df8a5ea634ed58 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-03di-0119000000-6d8f04ad8248965d46b9 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-0aor-6920000000-21ebdbb47b4df96c777c Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0a4i-0494000000-ee8e1bcd244f6e9a515f Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 195.3578174 predictedDarkChem Lite v0.1.0 [M+H]+ 196.1612174 predictedDarkChem Lite v0.1.0 [M+Na]+ 196.0240174 predictedDarkChem Lite v0.1.0
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Transcription factor binding
- Specific Function
- NAD-dependent protein deacetylase that links transcriptional regulation directly to intracellular energetics and participates in the coordination of several separated cellular functions such as cel...
- Gene Name
- SIRT1
- Uniprot ID
- Q96EB6
- Uniprot Name
- NAD-dependent protein deacetylase sirtuin-1
- Molecular Weight
- 81680.06 Da
References
- Heltweg B, Gatbonton T, Schuler AD, Posakony J, Li H, Goehle S, Kollipara R, Depinho RA, Gu Y, Simon JA, Bedalov A: Antitumor activity of a small-molecule inhibitor of human silent information regulator 2 enzymes. Cancer Res. 2006 Apr 15;66(8):4368-77. doi: 10.1158/0008-5472.CAN-05-3617. [Article]
- Med Chem Express: Cambinol Product Data Sheet [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- NAD-dependent protein deacetylase, which deacetylates internal lysines on histone and alpha-tubulin as well as many other proteins such as key transcription factors (PubMed:24177535, PubMed:12620231, PubMed:16648462, PubMed:18249187, PubMed:18332217, PubMed:18995842, PubMed:20587414, PubMed:21081649, PubMed:20543840, PubMed:22014574, PubMed:21726808, PubMed:21949390, PubMed:22771473, PubMed:23468428, PubMed:23908241, PubMed:24940000, PubMed:24769394, PubMed:24681946). Participates in the modulation of multiple and diverse biological processes such as cell cycle control, genomic integrity, microtubule dynamics, cell differentiation, metabolic networks, and autophagy. Plays a major role in the control of cell cycle progression and genomic stability. Functions in the antephase checkpoint preventing precocious mitotic entry in response to microtubule stress agents, and hence allowing proper inheritance of chromosomes. Positively regulates the anaphase promoting complex/cyclosome (APC/C) ubiquitin ligase complex activity by deacetylating CDC20 and FZR1, then allowing progression through mitosis. Associates both with chromatin at transcriptional start sites (TSSs) and enhancers of active genes. Plays a role in cell cycle and chromatin compaction through epigenetic modulation of the regulation of histone H4 'Lys-20' methylation (H4K20me1) during early mitosis. Specifically deacetylates histone H4 at 'Lys-16' (H4K16ac) between the G2/M transition and metaphase enabling H4K20me1 deposition by KMT5A leading to ulterior levels of H4K20me2 and H4K20me3 deposition throughout cell cycle, and mitotic S-phase progression (PubMed:23468428). Deacetylates KMT5A modulating KMT5A chromatin localization during the mitotic stress response (PubMed:23468428). Deacetylates also histone H3 at 'Lys-57' (H3K56ac) during the mitotic G2/M transition. Upon bacterium Listeria monocytogenes infection, deacetylates 'Lys-18' of histone H3 in a receptor tyrosine kinase MET- and PI3K/Akt-dependent manner, thereby inhibiting transcriptional activity and promoting late stages of listeria infection (PubMed:23908241). During oocyte meiosis progression, may deacetylate histone H4 at 'Lys-16' (H4K16ac) and alpha-tubulin, regulating spindle assembly and chromosome alignment by influencing microtubule dynamics and kinetochore function. Deacetylates histone H4 at 'Lys-16' (H4K16ac) at the VEGFA promoter and thereby contributes to regulate expression of VEGFA, a key regulator of angiogenesis (PubMed:24940000). Deacetylates alpha-tubulin at 'Lys-40' and hence controls neuronal motility, oligodendroglial cell arbor projection processes and proliferation of non-neuronal cells. Phosphorylation at Ser-368 by a G1/S-specific cyclin E-CDK2 complex inactivates SIRT2-mediated alpha-tubulin deacetylation, negatively regulating cell adhesion, cell migration and neurite outgrowth during neuronal differentiation. Deacetylates PARD3 and participates in the regulation of Schwann cell peripheral myelination formation during early postnatal development and during postinjury remyelination. Involved in several cellular metabolic pathways. Plays a role in the regulation of blood glucose homeostasis by deacetylating and stabilizing phosphoenolpyruvate carboxykinase PCK1 activity in response to low nutrient availability. Acts as a key regulator in the pentose phosphate pathway (PPP) by deacetylating and activating the glucose-6-phosphate G6PD enzyme, and therefore, stimulates the production of cytosolic NADPH to counteract oxidative damage. Maintains energy homeostasis in response to nutrient deprivation as well as energy expenditure by inhibiting adipogenesis and promoting lipolysis. Attenuates adipocyte differentiation by deacetylating and promoting FOXO1 interaction to PPARG and subsequent repression of PPARG-dependent transcriptional activity. Plays a role in the regulation of lysosome-mediated degradation of protein aggregates by autophagy in neuronal cells. Deacetylates FOXO1 in response to oxidative stress or serum deprivation, thereby negatively regulating FOXO1-mediated autophagy (PubMed:20543840). Deacetylates a broad range of transcription factors and co-regulators regulating target gene expression. Deacetylates transcriptional factor FOXO3 stimulating the ubiquitin ligase SCF(SKP2)-mediated FOXO3 ubiquitination and degradation (By similarity). Deacetylates HIF1A and therefore promotes HIF1A degradation and inhibition of HIF1A transcriptional activity in tumor cells in response to hypoxia (PubMed:24681946). Deacetylates RELA in the cytoplasm inhibiting NF-kappaB-dependent transcription activation upon TNF-alpha stimulation. Inhibits transcriptional activation by deacetylating p53/TP53 and EP300 (PubMed:18249187). Deacetylates also EIF5A (PubMed:22771473). Functions as a negative regulator on oxidative stress-tolerance in response to anoxia-reoxygenation conditions. Plays a role as tumor suppressor (PubMed:22014574).
- Specific Function
- Chromatin binding
- Gene Name
- SIRT2
- Uniprot ID
- Q8IXJ6
- Uniprot Name
- NAD-dependent protein deacetylase sirtuin-2
- Molecular Weight
- 43181.7 Da
References
- Heltweg B, Gatbonton T, Schuler AD, Posakony J, Li H, Goehle S, Kollipara R, Depinho RA, Gu Y, Simon JA, Bedalov A: Antitumor activity of a small-molecule inhibitor of human silent information regulator 2 enzymes. Cancer Res. 2006 Apr 15;66(8):4368-77. doi: 10.1158/0008-5472.CAN-05-3617. [Article]
- Med Chem Express: Cambinol Product Data Sheet [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- Curator comments
- Cambinol is said to be a weak inhibitor of SIRT5.
- General Function
- Zinc ion binding
- Specific Function
- NAD-dependent lysine demalonylase, desuccinylase and deglutarylase that specifically removes malonyl, succinyl and glutaryl groups on target proteins (PubMed:21908771, PubMed:22076378, PubMed:24703...
- Gene Name
- SIRT5
- Uniprot ID
- Q9NXA8
- Uniprot Name
- NAD-dependent protein deacylase sirtuin-5, mitochondrial
- Molecular Weight
- 33880.605 Da
References
- Heltweg B, Gatbonton T, Schuler AD, Posakony J, Li H, Goehle S, Kollipara R, Depinho RA, Gu Y, Simon JA, Bedalov A: Antitumor activity of a small-molecule inhibitor of human silent information regulator 2 enzymes. Cancer Res. 2006 Apr 15;66(8):4368-77. doi: 10.1158/0008-5472.CAN-05-3617. [Article]
- Med Chem Express: Cambinol Product Data Sheet [Link]
Drug created at September 16, 2019 14:46 / Updated at June 12, 2020 16:53