NAV

AN-9

Identification

Generic Name
AN-9
DrugBank Accession Number
DB05103
Background

Pivaloyloxymethyl butyrate (AN-9), an acyloxyalkyl ester prodrug of butyric acid (BA), exhibited low toxicity and significant anticancer activity in vitro and in vivo. It shows greater potency than BA at inducing malignant cell differentiation and tumor growth inhibition and has demonstrated more favorable toxicological, pharmacological, and pharmaceutical properties than BA in preclinical studies.

Type
Small Molecule
Groups
Investigational
Structure
3D
Similar Structures
Weight
Average: 202.25
Monoisotopic: 202.12050906
Chemical Formula
C10H18O4
Synonyms
  • Pivaloyloxymethyl butyrate
  • Pivaloyloxymethylbutyrate
  • Pivanex
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Pharmacology

Indication

Investigated for use/treatment in liver cancer, lung cancer, melanoma, and leukemia (lymphoid).

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Contraindications & Blackbox Warnings
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Pharmacodynamics

Not Available

Mechanism of action

Pivaloyloxymethyl butyrate is a histone deacetylase inhibitor analog of butyric acid that causes apoptosis of cancer cells through signaling cellular differentiation. It is rapidly and extensively transported intracellularly because of its high lipophilicity, where it undergoes esterase-mediated hydrolysis to form pivalic acid, formaldehyde, and BA.

TargetActionsOrganism
AApoptosis regulator Bcl-2
downregulator
Humans
ACaspase-8
regulator
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

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

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International/Other Brands
Pivanex

Categories

Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as fatty acid esters. These are carboxylic ester derivatives of a fatty acid.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Fatty Acyls
Sub Class
Fatty acid esters
Direct Parent
Fatty acid esters
Alternative Parents
Acylals / Dicarboxylic acids and derivatives / Acetals / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
Substituents
Acetal / Acylal / Aliphatic acyclic compound / Carbonyl group / Carboxylic acid derivative / Carboxylic acid ester / Dicarboxylic acid or derivatives / Fatty acid ester / Hydrocarbon derivative / Organic oxide
Molecular Framework
Aliphatic acyclic compounds
External Descriptors
Not Available
Affected organisms
Not Available

Chemical Identifiers

UNII
55VNK5440P
CAS number
122110-53-6
InChI Key
GYKLFBYWXZYSOW-UHFFFAOYSA-N
InChI
InChI=1S/C10H18O4/c1-5-6-8(11)13-7-14-9(12)10(2,3)4/h5-7H2,1-4H3
IUPAC Name
[(2,2-dimethylpropanoyl)oxy]methyl butanoate
SMILES
CCCC(=O)OCOC(=O)C(C)(C)C

References

General References
  1. Patnaik A, Rowinsky EK, Villalona MA, Hammond LA, Britten CD, Siu LL, Goetz A, Felton SA, Burton S, Valone FH, Eckhardt SG: A phase I study of pivaloyloxymethyl butyrate, a prodrug of the differentiating agent butyric acid, in patients with advanced solid malignancies. Clin Cancer Res. 2002 Jul;8(7):2142-8. [Article]
  2. Reid T, Valone F, Lipera W, Irwin D, Paroly W, Natale R, Sreedharan S, Keer H, Lum B, Scappaticci F, Bhatnagar A: Phase II trial of the histone deacetylase inhibitor pivaloyloxymethyl butyrate (Pivanex, AN-9) in advanced non-small cell lung cancer. Lung Cancer. 2004 Sep;45(3):381-6. [Article]
PubChem Compound
60748
PubChem Substance
347827710
ChemSpider
54751
ChEMBL
CHEMBL100014
ZINC
ZINC000001545115

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentNon-Small Cell Lung Carcinoma1
2TerminatedTreatmentChronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma1
1, 2TerminatedTreatmentMalignant Melanoma1

Pharmacoeconomics

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

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility1.46 mg/mLALOGPS
logP2.28ALOGPS
logP2.73Chemaxon
logS-2.1ALOGPS
pKa (Strongest Basic)-6.8Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count2Chemaxon
Hydrogen Donor Count0Chemaxon
Polar Surface Area52.6 Å2Chemaxon
Rotatable Bond Count7Chemaxon
Refractivity50.6 m3·mol-1Chemaxon
Polarizability22.17 Å3Chemaxon
Number of Rings0Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-0a4i-9100000000-36b8a4ab4384a71e5324
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0ukl-9310000000-a9f2f16ded8f282a6b7e
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0f6x-9400000000-48e988b0b0c33a84c47b
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a4i-9000000000-957fc7b41809b5a100a9
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0f6x-9500000000-48322479f30ffb040c4a
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-052f-9000000000-7b2b3db169482440e4b3
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-014i-9100000000-64fb1375b35877af6c17
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-151.8778294
predicted
DarkChem Lite v0.1.0
[M-H]-145.30452
predicted
DeepCCS 1.0 (2019)
[M+H]+151.6905294
predicted
DarkChem Lite v0.1.0
[M+H]+147.66252
predicted
DeepCCS 1.0 (2019)
[M+Na]+151.5892294
predicted
DarkChem Lite v0.1.0
[M+Na]+155.14775
predicted
DeepCCS 1.0 (2019)

Targets

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Details1. Apoptosis regulator Bcl-2
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Downregulator
General Function
Ubiquitin protein ligase binding
Specific Function
Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells. Regulates cell death by controlling the mitochondrial membrane permeability. Appea...
Gene Name
BCL2
Uniprot ID
P10415
Uniprot Name
Apoptosis regulator Bcl-2
Molecular Weight
26265.66 Da
References
  1. Rabizadeh E, Bairey O, Aviram A, Ben-Dror I, Shaklai M, Zimra Y: Doxorubicin and a butyric acid derivative effectively reduce levels of BCL-2 protein in the cells of chronic lymphocytic leukemia patient. Eur J Haematol. 2001 Apr;66(4):263-71. doi: 10.1034/j.1600-0609.2001.066004263.x. [Article]
Details2. Caspase-8
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Regulator
General Function
Ubiquitin protein ligase binding
Specific Function
Most upstream protease of the activation cascade of caspases responsible for the TNFRSF6/FAS mediated and TNFRSF1A induced cell death. Binding to the adapter molecule FADD recruits it to either rec...
Gene Name
CASP8
Uniprot ID
Q14790
Uniprot Name
Caspase-8
Molecular Weight
55390.53 Da
References
  1. Entin-Meer M, Rephaeli A, Yang X, Nudelman A, VandenBerg SR, Haas-Kogan DA: Butyric acid prodrugs are histone deacetylase inhibitors that show antineoplastic activity and radiosensitizing capacity in the treatment of malignant gliomas. Mol Cancer Ther. 2005 Dec;4(12):1952-61. doi: 10.1158/1535-7163.MCT-05-0087. [Article]

Drug created at October 21, 2007 22:23 / Updated at June 27, 2022 17:29