Z-Val-Ala-Asp fluoromethyl ketone

Identification

Name
Z-Val-Ala-Asp fluoromethyl ketone
Accession Number
DB07744
Type
Small Molecule
Groups
Experimental
Description

Non-methylated, competitive, and irreversible inhibitor of caspase 1, as well as other caspases,1 which can be used directly with purified enzymes. It does not require an esterase to hydrolyze the O-methyl ester like the cell-permeable form, Z-Val-Ala-Asp(O-Me) fluoromethyl ketone.

Structure
Thumb
Synonyms
  • N-[(Benzyloxy)carbonyl]-L-valyl-N-[(2S)-1-carboxy-4-fluoro-3-oxo-2-butanyl]-L-alaninamide
  • Z-VAD-FMK
Categories
UNII
Not Available
CAS number
161401-82-7
Weight
Average: 453.467
Monoisotopic: 453.191128417
Chemical Formula
C21H28FN3O7
InChI Key
SUUHZYLYARUNIA-YEWWUXTCSA-N
InChI
InChI=1S/C21H28FN3O7/c1-12(2)18(25-21(31)32-11-14-7-5-4-6-8-14)20(30)23-13(3)19(29)24-15(9-17(27)28)16(26)10-22/h4-8,12-13,15,18H,9-11H2,1-3H3,(H,23,30)(H,24,29)(H,25,31)(H,27,28)/t13-,15-,18-/m0/s1
IUPAC Name
(3S)-3-{[(2S)-2-{[(2S)-2-{[(benzyloxy)(hydroxy)methylidene]amino}-1-hydroxy-3-methylbutylidene]amino}-1-hydroxypropylidene]amino}-5-fluoro-4-oxopentanoic acid
SMILES
[H][[email protected]@](C)(N=C(O)[[email protected]@]([H])(N=C(O)OCC1=CC=CC=C1)C(C)C)C(O)=N[[email protected]@]([H])(CC(O)=O)C(=O)CF

Pharmacology

Indication
Not Available
Structured Indications
Not Available
Pharmacodynamics
Not Available
Mechanism of action
TargetActionsOrganism
UCaspase-1Not AvailableHuman
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
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AbacavirThe serum concentration of Abacavir can be decreased when it is combined with Z-Val-Ala-Asp fluoromethyl ketone.Approved, Investigational
AlfuzosinThe serum concentration of Alfuzosin can be increased when it is combined with Z-Val-Ala-Asp fluoromethyl ketone.Approved, Investigational
AlprazolamThe serum concentration of Alprazolam can be increased when it is combined with Z-Val-Ala-Asp fluoromethyl ketone.Approved, Illicit, Investigational
Ambroxol acefyllinateThe serum concentration of Ambroxol acefyllinate can be decreased when it is combined with Z-Val-Ala-Asp fluoromethyl ketone.Experimental, Investigational
AmineptineThe serum concentration of Amineptine can be increased when it is combined with Z-Val-Ala-Asp fluoromethyl ketone.Illicit, Withdrawn
AminophyllineThe serum concentration of Aminophylline can be decreased when it is combined with Z-Val-Ala-Asp fluoromethyl ketone.Approved
AmitriptylineThe serum concentration of Amitriptyline can be increased when it is combined with Z-Val-Ala-Asp fluoromethyl ketone.Approved
AmoxapineThe serum concentration of Amoxapine can be increased when it is combined with Z-Val-Ala-Asp fluoromethyl ketone.Approved
AtorvastatinThe serum concentration of Atorvastatin can be increased when it is combined with Z-Val-Ala-Asp fluoromethyl ketone.Approved
BoceprevirThe serum concentration of Z-Val-Ala-Asp fluoromethyl ketone can be decreased when it is combined with Boceprevir.Approved, Withdrawn
BromocriptineThe serum concentration of Bromocriptine can be increased when it is combined with Z-Val-Ala-Asp fluoromethyl ketone.Approved, Investigational
CabergolineThe serum concentration of Cabergoline can be increased when it is combined with Z-Val-Ala-Asp fluoromethyl ketone.Approved
CarbamazepineThe metabolism of Z-Val-Ala-Asp fluoromethyl ketone can be increased when combined with Carbamazepine.Approved, Investigational
ChlorotrianiseneThe serum concentration of Chlorotrianisene can be decreased when it is combined with Z-Val-Ala-Asp fluoromethyl ketone.Investigational, Withdrawn
ClarithromycinThe therapeutic efficacy of Clarithromycin can be decreased when used in combination with Z-Val-Ala-Asp fluoromethyl ketone.Approved
ClomipramineThe serum concentration of Clomipramine can be increased when it is combined with Z-Val-Ala-Asp fluoromethyl ketone.Approved, Vet Approved
Conjugated estrogensThe serum concentration of Conjugated estrogens can be decreased when it is combined with Z-Val-Ala-Asp fluoromethyl ketone.Approved
CyclobenzaprineThe serum concentration of Cyclobenzaprine can be increased when it is combined with Z-Val-Ala-Asp fluoromethyl ketone.Approved
CyclophosphamideThe risk or severity of adverse effects can be increased when Z-Val-Ala-Asp fluoromethyl ketone is combined with Cyclophosphamide.Approved, Investigational
CyclosporineThe serum concentration of Cyclosporine can be increased when it is combined with Z-Val-Ala-Asp fluoromethyl ketone.Approved, Investigational, Vet Approved
DelavirdineThe serum concentration of Delavirdine can be decreased when it is combined with Z-Val-Ala-Asp fluoromethyl ketone.Approved
DesipramineThe serum concentration of Desipramine can be increased when it is combined with Z-Val-Ala-Asp fluoromethyl ketone.Approved
DibenzepinThe serum concentration of Dibenzepin can be increased when it is combined with Z-Val-Ala-Asp fluoromethyl ketone.Experimental
DienestrolThe serum concentration of Dienestrol can be decreased when it is combined with Z-Val-Ala-Asp fluoromethyl ketone.Approved, Investigational
DiethylstilbestrolThe serum concentration of Diethylstilbestrol can be decreased when it is combined with Z-Val-Ala-Asp fluoromethyl ketone.Approved, Investigational
DigoxinThe serum concentration of Digoxin can be increased when it is combined with Z-Val-Ala-Asp fluoromethyl ketone.Approved
DihydroergotamineThe serum concentration of Dihydroergotamine can be increased when it is combined with Z-Val-Ala-Asp fluoromethyl ketone.Approved
DiltiazemThe metabolism of Diltiazem can be decreased when combined with Z-Val-Ala-Asp fluoromethyl ketone.Approved
DosulepinThe serum concentration of Dosulepin can be increased when it is combined with Z-Val-Ala-Asp fluoromethyl ketone.Approved
DoxepinThe serum concentration of Doxepin can be increased when it is combined with Z-Val-Ala-Asp fluoromethyl ketone.Approved
DyphyllineThe serum concentration of Dyphylline can be decreased when it is combined with Z-Val-Ala-Asp fluoromethyl ketone.Approved
EnfuvirtideThe serum concentration of Enfuvirtide can be increased when it is combined with Z-Val-Ala-Asp fluoromethyl ketone.Approved, Investigational
Ergoloid mesylateThe serum concentration of Ergoloid mesylate can be increased when it is combined with Z-Val-Ala-Asp fluoromethyl ketone.Approved
ErgonovineThe serum concentration of Ergonovine can be increased when it is combined with Z-Val-Ala-Asp fluoromethyl ketone.Approved
ErgotamineThe serum concentration of Ergotamine can be increased when it is combined with Z-Val-Ala-Asp fluoromethyl ketone.Approved
EsmirtazapineThe serum concentration of Esmirtazapine can be increased when it is combined with Z-Val-Ala-Asp fluoromethyl ketone.Investigational
EstradiolThe serum concentration of Estradiol can be decreased when it is combined with Z-Val-Ala-Asp fluoromethyl ketone.Approved, Investigational, Vet Approved
EstramustineThe serum concentration of Estramustine can be decreased when it is combined with Z-Val-Ala-Asp fluoromethyl ketone.Approved
Estrogens, esterifiedThe serum concentration of Estrogens, esterified can be decreased when it is combined with Z-Val-Ala-Asp fluoromethyl ketone.Approved
Estrone sulfateThe serum concentration of Estrone sulfate can be decreased when it is combined with Z-Val-Ala-Asp fluoromethyl ketone.Approved
Ethinyl EstradiolThe serum concentration of Ethinyl Estradiol can be decreased when it is combined with Z-Val-Ala-Asp fluoromethyl ketone.Approved
EtravirineThe serum concentration of Etravirine can be decreased when it is combined with Z-Val-Ala-Asp fluoromethyl ketone.Approved
GarlicThe serum concentration of Z-Val-Ala-Asp fluoromethyl ketone can be decreased when it is combined with Garlic.Approved
HexestrolThe serum concentration of Hexestrol can be decreased when it is combined with Z-Val-Ala-Asp fluoromethyl ketone.Withdrawn
ImipramineThe serum concentration of Imipramine can be increased when it is combined with Z-Val-Ala-Asp fluoromethyl ketone.Approved
IprindoleThe serum concentration of Iprindole can be increased when it is combined with Z-Val-Ala-Asp fluoromethyl ketone.Experimental
LofepramineThe serum concentration of Lofepramine can be increased when it is combined with Z-Val-Ala-Asp fluoromethyl ketone.Experimental
LovastatinThe serum concentration of Lovastatin can be increased when it is combined with Z-Val-Ala-Asp fluoromethyl ketone.Approved, Investigational
MestranolThe serum concentration of Mestranol can be decreased when it is combined with Z-Val-Ala-Asp fluoromethyl ketone.Approved
MethallenestrilThe serum concentration of Methallenestril can be decreased when it is combined with Z-Val-Ala-Asp fluoromethyl ketone.Experimental
MethylergometrineThe serum concentration of Methylergometrine can be increased when it is combined with Z-Val-Ala-Asp fluoromethyl ketone.Approved
MidazolamThe serum concentration of Midazolam can be increased when it is combined with Z-Val-Ala-Asp fluoromethyl ketone.Approved, Illicit
MirtazapineThe serum concentration of Mirtazapine can be increased when it is combined with Z-Val-Ala-Asp fluoromethyl ketone.Approved
NefazodoneThe serum concentration of Nefazodone can be increased when it is combined with Z-Val-Ala-Asp fluoromethyl ketone.Approved, Withdrawn
NortriptylineThe serum concentration of Nortriptyline can be increased when it is combined with Z-Val-Ala-Asp fluoromethyl ketone.Approved
OpipramolThe serum concentration of Opipramol can be increased when it is combined with Z-Val-Ala-Asp fluoromethyl ketone.Investigational
PethidineThe risk or severity of adverse effects can be increased when Z-Val-Ala-Asp fluoromethyl ketone is combined with Pethidine.Approved
ProtriptylineThe serum concentration of Protriptyline can be increased when it is combined with Z-Val-Ala-Asp fluoromethyl ketone.Approved
RiociguatThe serum concentration of Riociguat can be increased when it is combined with Z-Val-Ala-Asp fluoromethyl ketone.Approved
RosuvastatinThe serum concentration of Rosuvastatin can be increased when it is combined with Z-Val-Ala-Asp fluoromethyl ketone.Approved
SildenafilThe serum concentration of Sildenafil can be increased when it is combined with Z-Val-Ala-Asp fluoromethyl ketone.Approved, Investigational
SimvastatinThe serum concentration of Simvastatin can be increased when it is combined with Z-Val-Ala-Asp fluoromethyl ketone.Approved
St. John's WortThe metabolism of Z-Val-Ala-Asp fluoromethyl ketone can be increased when combined with St. John's Wort.Investigational, Nutraceutical
Synthetic Conjugated Estrogens, AThe serum concentration of Synthetic Conjugated Estrogens, A can be decreased when it is combined with Z-Val-Ala-Asp fluoromethyl ketone.Approved
TacrolimusThe metabolism of Tacrolimus can be decreased when combined with Z-Val-Ala-Asp fluoromethyl ketone.Approved, Investigational
TemsirolimusThe risk or severity of adverse effects can be increased when Z-Val-Ala-Asp fluoromethyl ketone is combined with Temsirolimus.Approved
TheophyllineThe serum concentration of Theophylline can be decreased when it is combined with Z-Val-Ala-Asp fluoromethyl ketone.Approved
TianeptineThe serum concentration of Tianeptine can be increased when it is combined with Z-Val-Ala-Asp fluoromethyl ketone.Approved, Investigational
TipranavirThe serum concentration of Z-Val-Ala-Asp fluoromethyl ketone can be decreased when it is combined with Tipranavir.Approved, Investigational
TriazolamThe serum concentration of Triazolam can be increased when it is combined with Z-Val-Ala-Asp fluoromethyl ketone.Approved
TrimipramineThe serum concentration of Trimipramine can be increased when it is combined with Z-Val-Ala-Asp fluoromethyl ketone.Approved
Valproic AcidThe serum concentration of Valproic Acid can be decreased when it is combined with Z-Val-Ala-Asp fluoromethyl ketone.Approved, Investigational
VerapamilThe metabolism of Verapamil can be decreased when combined with Z-Val-Ala-Asp fluoromethyl ketone.Approved
ZidovudineThe serum concentration of Zidovudine can be decreased when it is combined with Z-Val-Ala-Asp fluoromethyl ketone.Approved
Food Interactions
Not Available

References

General References
Not Available
External Links
PubChem Compound
5497171
PubChem Substance
99444215
ChemSpider
4593739
ChEMBL
CHEMBL205821

Clinical Trials

Clinical Trials
Not Available

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 Solubility0.0435 mg/mLALOGPS
logP1.58ALOGPS
logP3.59ChemAxon
logS-4ALOGPS
pKa (Strongest Acidic)3.2ChemAxon
pKa (Strongest Basic)1.28ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count10ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area161.37 Å2ChemAxon
Rotatable Bond Count13ChemAxon
Refractivity111.2 m3·mol-1ChemAxon
Polarizability44.01 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.7761
Blood Brain Barrier-0.7676
Caco-2 permeable-0.784
P-glycoprotein substrateSubstrate0.5932
P-glycoprotein inhibitor INon-inhibitor0.6455
P-glycoprotein inhibitor IINon-inhibitor0.9201
Renal organic cation transporterNon-inhibitor0.9549
CYP450 2C9 substrateNon-substrate0.7854
CYP450 2D6 substrateNon-substrate0.7948
CYP450 3A4 substrateNon-substrate0.5648
CYP450 1A2 substrateNon-inhibitor0.7601
CYP450 2C9 inhibitorNon-inhibitor0.8935
CYP450 2D6 inhibitorNon-inhibitor0.9282
CYP450 2C19 inhibitorNon-inhibitor0.6948
CYP450 3A4 inhibitorNon-inhibitor0.6306
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.913
Ames testNon AMES toxic0.8032
CarcinogenicityNon-carcinogens0.878
BiodegradationNot ready biodegradable0.7344
Rat acute toxicity2.2208 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.989
hERG inhibition (predictor II)Non-inhibitor0.9409
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as hybrid peptides. These are compounds containing at least two different types of amino acids (alpha, beta, gamma, delta) linked to each other through a peptide bond.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Peptidomimetics
Sub Class
Hybrid peptides
Direct Parent
Hybrid peptides
Alternative Parents
Dipeptides / Valine and derivatives / N-acyl-alpha amino acids and derivatives / Alpha amino acid amides / Alanine and derivatives / Beta amino acids and derivatives / Benzyloxycarbonyls / Gamma-keto acids and derivatives / N-acyl amines / Alpha-haloketones
show 11 more
Substituents
Hybrid peptide / Alpha-dipeptide / Valine or derivatives / N-acyl-alpha amino acid or derivatives / Alpha-amino acid amide / Beta amino acid or derivatives / Alanine or derivatives / N-substituted-alpha-amino acid / Alpha-amino acid or derivatives / Benzyloxycarbonyl
show 29 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Endopeptidase activity
Specific Function
Thiol protease that cleaves IL-1 beta between an Asp and an Ala, releasing the mature cytokine which is involved in a variety of inflammatory processes. Important for defense against pathogens. Cle...
Gene Name
CASP1
Uniprot ID
P29466
Uniprot Name
Caspase-1
Molecular Weight
45158.215 Da
References
  1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]

Drug created on September 15, 2010 15:25 / Updated on December 01, 2017 15:55