Identification

Generic Name
TNP-470
DrugBank Accession Number
DB08633
Background

O-(chloroacetylcarbamoyl)fumagillol (TNP-470) has been used in trials studying the treatment of HIV Infections, Sarcoma, Kaposi, and Pancreatic Neoplasms.

Type
Small Molecule
Groups
Investigational
Structure
Weight
Average: 401.882
Monoisotopic: 401.16051534
Chemical Formula
C19H28ClNO6
Synonyms
  • O-(chloroacetylcarbamoyl)fumagillol
  • O-chloroacetylcarbamoylfumagillol
External IDs
  • AGM 1470
  • AGM-1470
  • DRG-0148
  • NSC-642492
  • TNP 470
  • TNP-470

Pharmacology

Indication

Not Available

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Contraindications & Blackbox Warnings
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Pharmacodynamics

Not Available

Mechanism of action
TargetActionsOrganism
UMethionine aminopeptidase 2Not AvailableHumans
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.
DrugInteraction
Alendronic acidThe risk or severity of jaw osteonecrosis and anti-angiogenesis can be increased when TNP-470 is combined with Alendronic acid.
Clodronic acidThe risk or severity of jaw osteonecrosis and anti-angiogenesis can be increased when TNP-470 is combined with Clodronic acid.
Darbepoetin alfaThe risk or severity of Thrombosis can be increased when Darbepoetin alfa is combined with TNP-470.
ErythropoietinThe risk or severity of Thrombosis can be increased when Erythropoietin is combined with TNP-470.
Etidronic acidThe risk or severity of jaw osteonecrosis and anti-angiogenesis can be increased when TNP-470 is combined with Etidronic acid.
IbandronateThe risk or severity of jaw osteonecrosis and anti-angiogenesis can be increased when TNP-470 is combined with Ibandronate.
Methoxy polyethylene glycol-epoetin betaThe risk or severity of Thrombosis can be increased when Methoxy polyethylene glycol-epoetin beta is combined with TNP-470.
Pamidronic acidThe risk or severity of jaw osteonecrosis and anti-angiogenesis can be increased when TNP-470 is combined with Pamidronic acid.
PeginesatideThe risk or severity of Thrombosis can be increased when Peginesatide is combined with TNP-470.
Risedronic acidThe risk or severity of jaw osteonecrosis and anti-angiogenesis can be increased when TNP-470 is combined with Risedronic acid.
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Food Interactions
Not Available

Categories

Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as carbamate esters. These are compounds containing an ester of carbamic acid with the general structure R2NC(=O)OR' (R' not H). They are esters of carbamic acids.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Carbamate esters
Alternative Parents
Dicarboximides / Organic carbonic acids and derivatives / Oxacyclic compounds / Epoxides / Dialkyl ethers / Organopnictogen compounds / Organonitrogen compounds / Organochlorides / Organic oxides / Hydrocarbon derivatives
show 2 more
Substituents
Aliphatic heteropolycyclic compound / Alkyl chloride / Alkyl halide / Carbamic acid ester / Carbonic acid derivative / Carbonyl group / Dialkyl ether / Dicarboximide / Ether / Hydrocarbon derivative
show 11 more
Molecular Framework
Aliphatic heteropolycyclic compounds
External Descriptors
Not Available
Affected organisms
Not Available

Chemical Identifiers

UNII
X47GR46481
CAS number
129298-91-5
InChI Key
MSHZHSPISPJWHW-PVDLLORBSA-N
InChI
InChI=1S/C19H28ClNO6/c1-11(2)5-6-13-18(3,27-13)16-15(24-4)12(7-8-19(16)10-25-19)26-17(23)21-14(22)9-20/h5,12-13,15-16H,6-10H2,1-4H3,(H,21,22,23)/t12-,13-,15-,16-,18+,19+/m1/s1
IUPAC Name
(3R,4S,5S,6R)-5-methoxy-4-[(2R,3R)-2-methyl-3-(3-methylbut-2-en-1-yl)oxiran-2-yl]-1-oxaspiro[2.5]octan-6-yl N-(2-chloroacetyl)carbamate
SMILES
[H][C@]1(CC=C(C)C)O[C@]1(C)[C@@]1([H])[C@]([H])(OC)[C@@]([H])(CC[C@]11CO1)OC(=O)NC(=O)CCl

References

General References
Not Available
PubChem Compound
369976
PubChem Substance
99445104
ChemSpider
328427
BindingDB
17446
ChEBI
90748
ChEMBL
CHEMBL424278
ZINC
ZINC000003914617
PDBe Ligand
TN4

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2TerminatedTreatmentNeoplasms, Pancreatic1
1CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Kaposi’s sarcoma1

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 Solubility0.0234 mg/mLALOGPS
logP2.52ALOGPS
logP2.24ChemAxon
logS-4.2ALOGPS
pKa (Strongest Acidic)9.71ChemAxon
pKa (Strongest Basic)-3.7ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area89.69 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity98.45 m3·mol-1ChemAxon
Polarizability41.46 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9886
Blood Brain Barrier+0.7707
Caco-2 permeable-0.5611
P-glycoprotein substrateSubstrate0.647
P-glycoprotein inhibitor IInhibitor0.7156
P-glycoprotein inhibitor IIInhibitor0.5513
Renal organic cation transporterNon-inhibitor0.8603
CYP450 2C9 substrateNon-substrate0.8027
CYP450 2D6 substrateNon-substrate0.8334
CYP450 3A4 substrateSubstrate0.7758
CYP450 1A2 substrateNon-inhibitor0.6951
CYP450 2C9 inhibitorNon-inhibitor0.7222
CYP450 2D6 inhibitorNon-inhibitor0.8919
CYP450 2C19 inhibitorNon-inhibitor0.6379
CYP450 3A4 inhibitorNon-inhibitor0.5666
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7177
Ames testAMES toxic0.5347
CarcinogenicityNon-carcinogens0.828
BiodegradationNot ready biodegradable0.9852
Rat acute toxicity2.8117 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9776
hERG inhibition (predictor II)Non-inhibitor0.8006
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

Targets

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Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Poly(a) rna binding
Specific Function
Cotranslationally removes the N-terminal methionine from nascent proteins. The N-terminal methionine is often cleaved when the second residue in the primary sequence is small and uncharged (Met-Ala...
Gene Name
METAP2
Uniprot ID
P50579
Uniprot Name
Methionine aminopeptidase 2
Molecular Weight
52891.145 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. [Article]

Drug created at September 15, 2010 21:33 / Updated at June 12, 2020 16:52