Prinomastat

Identification

Name
Prinomastat
Accession Number
DB05100
Type
Small Molecule
Groups
Investigational
Description

Prinomastat is a synthetic hydroxamic acid derivative with potential antineoplastic activity. Prinomastat inhibits matrix metalloproteinases (MMPs) (specifically, MMP-2, 9, 13, and 14), thereby inducing extracellular matrix degradation, and inhibiting angiogenesis, tumor growth and invasion, and metastasis. As a lipophilic agent, prinomastat crosses the blood-brain barrier.

Structure
Thumb
Synonyms
Not Available
External IDs
AG-3340 / AG3340 / KB-R-9896
International/Other Brands
Prinomastat
Categories
UNII
10T6626FRK
CAS number
192329-42-3
Weight
Average: 423.506
Monoisotopic: 423.092262177
Chemical Formula
C18H21N3O5S2
InChI Key
YKPYIPVDTNNYCN-INIZCTEOSA-N
InChI
InChI=1S/C18H21N3O5S2/c1-18(2)16(17(22)20-23)21(11-12-27-18)28(24,25)15-5-3-13(4-6-15)26-14-7-9-19-10-8-14/h3-10,16,23H,11-12H2,1-2H3,(H,20,22)/t16-/m0/s1
IUPAC Name
3-N-hydroxy(3S)-2,2-dimethyl-4-[4-(pyridin-4-yloxy)benzenesulfonyl]thiomorpholine-3-carboximidic acid
SMILES
[H][C@]1(N(CCSC1(C)C)S(=O)(=O)C1=CC=C(OC2=CC=NC=C2)C=C1)C(O)=NO

Pharmacology

Indication

Investigated for use/treatment in brain cancer, lung cancer, and prostate cancer.

Pharmacodynamics
Not Available
Mechanism of action
Not Available
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life

2-5 hours

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 Prinomastat.Approved, Investigational
AlfuzosinThe serum concentration of Alfuzosin can be increased when it is combined with Prinomastat.Approved, Investigational
AlprazolamThe serum concentration of Alprazolam can be increased when it is combined with Prinomastat.Approved, Illicit, Investigational
Ambroxol acefyllinateThe serum concentration of Ambroxol acefyllinate can be decreased when it is combined with Prinomastat.Experimental, Investigational
AmineptineThe serum concentration of Amineptine can be increased when it is combined with Prinomastat.Illicit, Withdrawn
AminophyllineThe serum concentration of Aminophylline can be decreased when it is combined with Prinomastat.Approved
AmitriptylineThe serum concentration of Amitriptyline can be increased when it is combined with Prinomastat.Approved
AmitriptylinoxideThe serum concentration of Amitriptylinoxide can be increased when it is combined with Prinomastat.Approved, Investigational
AmoxapineThe serum concentration of Amoxapine can be increased when it is combined with Prinomastat.Approved
BoceprevirThe serum concentration of Prinomastat can be decreased when it is combined with Boceprevir.Approved, Withdrawn
BromocriptineThe serum concentration of Bromocriptine can be increased when it is combined with Prinomastat.Approved, Investigational
ButriptylineThe serum concentration of Butriptyline can be increased when it is combined with Prinomastat.Approved
CabergolineThe serum concentration of Cabergoline can be increased when it is combined with Prinomastat.Approved
CarbamazepineThe metabolism of Prinomastat can be increased when combined with Carbamazepine.Approved, Investigational
ClarithromycinThe therapeutic efficacy of Clarithromycin can be decreased when used in combination with Prinomastat.Approved
ClomipramineThe serum concentration of Clomipramine can be increased when it is combined with Prinomastat.Approved, Investigational, Vet Approved
CyclophosphamideThe risk or severity of adverse effects can be increased when Prinomastat is combined with Cyclophosphamide.Approved, Investigational
CyclosporineThe serum concentration of Cyclosporine can be increased when it is combined with Prinomastat.Approved, Investigational, Vet Approved
DelavirdineThe serum concentration of Delavirdine can be decreased when it is combined with Prinomastat.Approved
DesipramineThe serum concentration of Desipramine can be increased when it is combined with Prinomastat.Approved, Investigational
DibenzepinThe serum concentration of Dibenzepin can be increased when it is combined with Prinomastat.Experimental
DiethylstilbestrolThe serum concentration of Diethylstilbestrol can be decreased when it is combined with Prinomastat.Approved, Investigational
DigoxinThe serum concentration of Digoxin can be increased when it is combined with Prinomastat.Approved
DihydroergotamineThe serum concentration of Dihydroergotamine can be increased when it is combined with Prinomastat.Approved, Investigational
DiltiazemThe metabolism of Diltiazem can be decreased when combined with Prinomastat.Approved, Investigational
DimetacrineThe serum concentration of Dimetacrine can be increased when it is combined with Prinomastat.Approved, Withdrawn
DosulepinThe serum concentration of Dosulepin can be increased when it is combined with Prinomastat.Approved
DoxepinThe serum concentration of Doxepin can be increased when it is combined with Prinomastat.Approved, Investigational
DyphyllineThe serum concentration of Dyphylline can be decreased when it is combined with Prinomastat.Approved
EnfuvirtideThe serum concentration of Enfuvirtide can be increased when it is combined with Prinomastat.Approved, Investigational
Ergoloid mesylateThe serum concentration of Ergoloid mesylate can be increased when it is combined with Prinomastat.Approved
ErgonovineThe serum concentration of Ergonovine can be increased when it is combined with Prinomastat.Approved
ErgotamineThe serum concentration of Ergotamine can be increased when it is combined with Prinomastat.Approved
EstradiolThe serum concentration of Estradiol can be decreased when it is combined with Prinomastat.Approved, Investigational, Vet Approved
Estradiol cypionateThe serum concentration of Estradiol cypionate can be decreased when it is combined with Prinomastat.Approved, Investigational, Vet Approved
Estradiol valerateThe serum concentration of Estradiol valerate can be decreased when it is combined with Prinomastat.Approved, Investigational, Vet Approved
Ethinyl EstradiolThe serum concentration of Ethinyl Estradiol can be decreased when it is combined with Prinomastat.Approved
EtravirineThe serum concentration of Etravirine can be decreased when it is combined with Prinomastat.Approved
GarlicThe serum concentration of Prinomastat can be decreased when it is combined with Garlic.Approved, Nutraceutical
ImipramineThe serum concentration of Imipramine can be increased when it is combined with Prinomastat.Approved
IprindoleThe serum concentration of Iprindole can be increased when it is combined with Prinomastat.Experimental
LofepramineThe serum concentration of Lofepramine can be increased when it is combined with Prinomastat.Experimental
LovastatinThe serum concentration of Lovastatin can be increased when it is combined with Prinomastat.Approved, Investigational
MelitracenThe serum concentration of Melitracen can be increased when it is combined with Prinomastat.Experimental, Investigational
MestranolThe serum concentration of Mestranol can be decreased when it is combined with Prinomastat.Approved
MethylergometrineThe serum concentration of Methylergometrine can be increased when it is combined with Prinomastat.Approved
MidazolamThe serum concentration of Midazolam can be increased when it is combined with Prinomastat.Approved, Illicit
NefazodoneThe serum concentration of Nefazodone can be increased when it is combined with Prinomastat.Approved, Withdrawn
NortriptylineThe serum concentration of Nortriptyline can be increased when it is combined with Prinomastat.Approved
OpipramolThe serum concentration of Opipramol can be increased when it is combined with Prinomastat.Investigational
PethidineThe risk or severity of adverse effects can be increased when Prinomastat is combined with Pethidine.Approved
ProtriptylineThe serum concentration of Protriptyline can be increased when it is combined with Prinomastat.Approved
RiociguatThe serum concentration of Riociguat can be increased when it is combined with Prinomastat.Approved
SildenafilThe serum concentration of Sildenafil can be increased when it is combined with Prinomastat.Approved, Investigational
SimvastatinThe serum concentration of Simvastatin can be increased when it is combined with Prinomastat.Approved
St. John's WortThe metabolism of Prinomastat can be increased when combined with St. John's Wort.Approved, Investigational, Nutraceutical
TacrolimusThe metabolism of Tacrolimus can be decreased when combined with Prinomastat.Approved, Investigational
TemsirolimusThe risk or severity of adverse effects can be increased when Prinomastat is combined with Temsirolimus.Approved
TheophyllineThe serum concentration of Theophylline can be decreased when it is combined with Prinomastat.Approved
TianeptineThe serum concentration of Tianeptine can be increased when it is combined with Prinomastat.Approved, Investigational
TipranavirThe serum concentration of Prinomastat can be decreased when it is combined with Tipranavir.Approved, Investigational
TriazolamThe serum concentration of Triazolam can be increased when it is combined with Prinomastat.Approved, Investigational
TrimipramineThe serum concentration of Trimipramine can be increased when it is combined with Prinomastat.Approved
Valproic AcidThe serum concentration of Valproic Acid can be decreased when it is combined with Prinomastat.Approved, Investigational
VerapamilThe metabolism of Verapamil can be decreased when combined with Prinomastat.Approved
ZidovudineThe serum concentration of Zidovudine can be decreased when it is combined with Prinomastat.Approved
Food Interactions
Not Available

References

General References
  1. Shalinsky DR, Brekken J, Zou H, McDermott CD, Forsyth P, Edwards D, Margosiak S, Bender S, Truitt G, Wood A, Varki NM, Appelt K: Broad antitumor and antiangiogenic activities of AG3340, a potent and selective MMP inhibitor undergoing advanced oncology clinical trials. Ann N Y Acad Sci. 1999 Jun 30;878:236-70. [PubMed:10415735]
  2. Deryugina EI, Ratnikov BI, Strongin AY: Prinomastat, a hydroxamate inhibitor of matrix metalloproteinases, has a complex effect on migration of breast carcinoma cells. Int J Cancer. 2003 May 1;104(5):533-41. [PubMed:12594807]
  3. Scatena R: Prinomastat, a hydroxamate-based matrix metalloproteinase inhibitor. A novel pharmacological approach for tissue remodelling-related diseases. Expert Opin Investig Drugs. 2000 Sep;9(9):2159-65. [PubMed:11060800]
External Links
PubChem Compound
466151
PubChem Substance
175426943
ChemSpider
409762
BindingDB
50082556
ChEBI
138885
ChEMBL
CHEMBL75094
HET
PN0
Wikipedia
Prinomastat
PDB Entries
3qm4 / 3tda

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentBrain and Central Nervous System Tumors1
3CompletedTreatmentLung Cancers1
3CompletedTreatmentProstate Cancer1

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 Solubility0.0464 mg/mLALOGPS
logP1.79ALOGPS
logP0.94ChemAxon
logS-4ALOGPS
pKa (Strongest Acidic)4.42ChemAxon
pKa (Strongest Basic)5.95ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area112.32 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity106.39 m3·mol-1ChemAxon
Polarizability40.86 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9508
Blood Brain Barrier-0.5364
Caco-2 permeable-0.6419
P-glycoprotein substrateNon-substrate0.7148
P-glycoprotein inhibitor INon-inhibitor0.6303
P-glycoprotein inhibitor IINon-inhibitor0.6027
Renal organic cation transporterNon-inhibitor0.8762
CYP450 2C9 substrateNon-substrate0.717
CYP450 2D6 substrateNon-substrate0.8124
CYP450 3A4 substrateNon-substrate0.5304
CYP450 1A2 substrateNon-inhibitor0.734
CYP450 2C9 inhibitorNon-inhibitor0.6707
CYP450 2D6 inhibitorNon-inhibitor0.8338
CYP450 2C19 inhibitorNon-inhibitor0.5746
CYP450 3A4 inhibitorNon-inhibitor0.8131
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6747
Ames testNon AMES toxic0.616
CarcinogenicityNon-carcinogens0.5532
BiodegradationNot ready biodegradable0.9971
Rat acute toxicity2.4167 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8634
hERG inhibition (predictor II)Non-inhibitor0.6423
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 diarylethers. These are organic compounds containing the dialkyl ether functional group, with the formula ROR', where R and R' are aryl groups.
Kingdom
Organic compounds
Super Class
Organic oxygen compounds
Class
Organooxygen compounds
Sub Class
Ethers
Direct Parent
Diarylethers
Alternative Parents
Alpha amino acids and derivatives / Benzenesulfonamides / Benzenesulfonyl compounds / Phenoxy compounds / Phenol ethers / Thiomorpholines / Pyridines and derivatives / Organosulfonamides / Sulfonyls / Heteroaromatic compounds
show 8 more
Substituents
Diaryl ether / Alpha-amino acid or derivatives / Benzenesulfonamide / Benzenesulfonyl group / Phenoxy compound / Phenol ether / Monocyclic benzene moiety / Pyridine / Benzenoid / 1,4-thiazinane
show 19 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not Available

Drug created on October 21, 2007 16:23 / Updated on June 02, 2018 07:37