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
DrugInteraction
AbacavirThe serum concentration of Abacavir can be decreased when it is combined with Prinomastat.
Ambroxol acefyllinateThe serum concentration of Ambroxol acefyllinate can be decreased when it is combined with Prinomastat.
AmineptineThe serum concentration of Amineptine can be increased when it is combined with Prinomastat.
AminophyllineThe serum concentration of Aminophylline can be decreased when it is combined with Prinomastat.
AmitriptylinoxideThe serum concentration of Amitriptylinoxide can be increased when it is combined with Prinomastat.
AmoxapineThe serum concentration of Amoxapine can be increased when it is combined with Prinomastat.
BoceprevirThe serum concentration of Prinomastat can be decreased when it is combined with Boceprevir.
ButriptylineThe serum concentration of Butriptyline can be increased when it is combined with Prinomastat.
ClarithromycinThe therapeutic efficacy of Clarithromycin can be decreased when used in combination with Prinomastat.
ClomipramineThe serum concentration of Clomipramine can be increased when it is combined with Prinomastat.
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 August 02, 2018 05:29