Cambinol

Identification

Name
Cambinol
Accession Number
DB15493
Description

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
Thumb
Weight
Average: 360.43
Monoisotopic: 360.093248937
Chemical Formula
C21H16N2O2S
Synonyms
Not Available
External IDs
  • HY-100732

Pharmacology

Indication
Not Available
Contraindications & Blackbox Warnings
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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

TargetActionsOrganism
ANAD-dependent protein deacetylase sirtuin-1
inhibitor
Humans
ANAD-dependent protein deacetylase sirtuin-2
inhibitor
Humans
NNAD-dependent protein deacylase sirtuin-5, mitochondrial
inhibitor
Humans
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
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Toxicity
Not Available
Affected organisms
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

Products

Categories

Drug Categories
Classification
Not classified

Chemical Identifiers

UNII
Not Available
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
  1. 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. [PubMed:16618762]
  2. Med Chem Express: Cambinol Product Data Sheet [Link]
ChemSpider
2497101
BindingDB
29040
ChEMBL
CHEMBL491960
ZINC
ZINC000007996283

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Not Available
Experimental Properties
PropertyValueSource
water solubility<0.1mg/mLMed Chem Express: Cambinol Product Data Sheet
Predicted Properties
PropertyValueSource
Water Solubility0.00319 mg/mLALOGPS
logP4.01ALOGPS
logP3.99ChemAxon
logS-5ALOGPS
pKa (Strongest Acidic)7.96ChemAxon
pKa (Strongest Basic)-2.8ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area61.36 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity107.13 m3·mol-1ChemAxon
Polarizability37.57 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Targets

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
  1. 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. [PubMed:16618762]
  2. 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
  1. 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. [PubMed:16618762]
  2. 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
  1. 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. [PubMed:16618762]
  2. Med Chem Express: Cambinol Product Data Sheet [Link]

Drug created on September 16, 2019 08:46 / Updated on June 12, 2020 10:53

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