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Identification
NameABT-510
Accession NumberDB05434
TypeSmall Molecule
GroupsInvestigational
Description

ABT-510 is peptide mimetics of thrombospondin-1 (TSP-1), block angiogenesis in vitro and in vivo and slow tumor growth. It is developed by Abbott Laboratories for the treatment of Solid Tumors, Lymphoma and Melanoma.

Structure
Thumb
SynonymsNot Available
External Identifiers Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
CategoriesNot Available
UNIICRR8E37XOB
CAS numberNot Available
WeightAverage: 994.2317
Monoisotopic: 993.633500563
Chemical FormulaC46H83N13O11
InChI KeyInChIKey=RIWLPSIAFBLILR-WVNGMBSFSA-N
InChI
InChI=1S/C46H83N13O11/c1-12-18-30(39(64)55-36(26(7)13-2)42(67)53-31(19-16-21-50-46(47)48)45(70)59-22-17-20-32(59)40(65)49-15-4)52-44(69)38(28(9)60)57-43(68)37(27(8)14-3)56-41(66)35(25(5)6)54-33(62)23-51-34(63)24-58(11)29(10)61/h25-28,30-32,35-38,60H,12-24H2,1-11H3,(H,49,65)(H,51,63)(H,52,69)(H,53,67)(H,54,62)(H,55,64)(H,56,66)(H,57,68)(H4,47,48,50)/t26-,27-,28+,30-,31-,32-,35-,36-,37+,38-/m0/s1
IUPAC Name
(2S)-1-[(2S)-5-[(diaminomethylidene)amino]-2-[(2S,3S)-2-[(2S)-2-[(2S,3R)-3-hydroxy-2-[(2R,3S)-3-methyl-2-[(2S)-3-methyl-2-{2-[2-(N-methylacetamido)acetamido]acetamido}butanamido]pentanamido]butanamido]pentanamido]-3-methylpentanamido]pentanoyl]-N-ethylpyrrolidine-2-carboxamide
SMILES
CCC[[email protected]](NC(=O)[C@@H](NC(=O)[[email protected]](NC(=O)[C@@H](NC(=O)CNC(=O)CN(C)C(C)=O)C(C)C)[C@@H](C)CC)[C@@H](C)O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1CCC[[email protected]]1C(=O)NCC
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as n-acyl-alpha amino acids and derivatives. These are compounds containing an alpha amino acid (or a derivative thereof) which bears an acyl group at its terminal nitrogen atom.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentN-acyl-alpha amino acids and derivatives
Alternative Parents
Substituents
  • N-acyl-alpha amino acid or derivatives
  • Alpha-amino acid amide
  • Pyrrolidine-2-carboxamide
  • Pyrrolidine carboxylic acid or derivatives
  • N-acylpyrrolidine
  • Fatty acyl
  • N-acyl-amine
  • Fatty amide
  • Acetamide
  • Tertiary carboxylic acid amide
  • Pyrrolidine
  • Tertiary amine
  • Secondary carboxylic acid amide
  • Secondary alcohol
  • Guanidine
  • Carboxamide group
  • Azacycle
  • Organoheterocyclic compound
  • Organic 1,3-dipolar compound
  • Propargyl-type 1,3-dipolar organic compound
  • Carboximidamide
  • Carboxylic acid amide
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Alcohol
  • Aliphatic heteromonocyclic compound
Molecular FrameworkAliphatic heteromonocyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationInvestigated for use/treatment in lymphoma (unspecified), melanoma, and solid tumors.
PharmacodynamicsNot Available
Mechanism of actionABT-510 is a synthetic peptide that mimics the anti-angiogenic activity of the naturally occurring protein, thrombospondin-1 (TSP-1). Angiogenesis is the process of new blood vessel formation. ABT-510 blocks the actions of multiple pro-angiogenic growth factors known to play a role in cancer related blood vessel growth, such as VEGF, bFGF, HGF, and IL-8. ABT-510 is the first compound with this mechanism of action to be studied.
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organismsNot Available
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.8943
Blood Brain Barrier-0.9627
Caco-2 permeable-0.7358
P-glycoprotein substrateSubstrate0.895
P-glycoprotein inhibitor INon-inhibitor0.5629
P-glycoprotein inhibitor IINon-inhibitor0.6938
Renal organic cation transporterNon-inhibitor0.8488
CYP450 2C9 substrateNon-substrate0.846
CYP450 2D6 substrateNon-substrate0.7697
CYP450 3A4 substrateSubstrate0.5159
CYP450 1A2 substrateNon-inhibitor0.8674
CYP450 2C9 inhibitorNon-inhibitor0.8617
CYP450 2D6 inhibitorNon-inhibitor0.8883
CYP450 2C19 inhibitorNon-inhibitor0.8217
CYP450 3A4 inhibitorNon-inhibitor0.9247
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9937
Ames testNon AMES toxic0.7586
CarcinogenicityNon-carcinogens0.8557
BiodegradationReady biodegradable0.5262
Rat acute toxicity2.7475 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9101
hERG inhibition (predictor II)Non-inhibitor0.7714
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.0426 mg/mLALOGPS
logP1.08ALOGPS
logP-3.3ChemAxon
logS-4.4ALOGPS
pKa (Strongest Acidic)10.73ChemAxon
pKa (Strongest Basic)11.56ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count14ChemAxon
Hydrogen Donor Count11ChemAxon
Polar Surface Area358.05 Å2ChemAxon
Rotatable Bond Count30ChemAxon
Refractivity257.8 m3·mol-1ChemAxon
Polarizability107.34 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
General References
  1. Rusk A, McKeegan E, Haviv F, Majest S, Henkin J, Khanna C: Preclinical evaluation of antiangiogenic thrombospondin-1 peptide mimetics, ABT-526 and ABT-510, in companion dogs with naturally occurring cancers. Clin Cancer Res. 2006 Dec 15;12(24):7444-55. [PubMed:17189418 ]
  2. Gietema JA, Hoekstra R, de Vos FY, Uges DR, van der Gaast A, Groen HJ, Loos WJ, Knight RA, Carr RA, Humerickhouse RA, Eskens FA: A phase I study assessing the safety and pharmacokinetics of the thrombospondin-1-mimetic angiogenesis inhibitor ABT-510 with gemcitabine and cisplatin in patients with solid tumors. Ann Oncol. 2006 Aug;17(8):1320-7. Epub 2006 May 25. [PubMed:16728485 ]
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Ligand-dependent nuclear receptor transcription coactivator activity
Specific Function:
Plays an important role in the regulation of cell survival, cell division, angiogenesis, cell differentiation and cell migration. Functions as potent mitogen in vitro.
Gene Name:
FGF2
Uniprot ID:
P09038
Molecular Weight:
30769.715 Da
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Serine-type endopeptidase activity
Specific Function:
Potent mitogen for mature parenchymal hepatocyte cells, seems to be a hepatotrophic factor, and acts as a growth factor for a broad spectrum of tissues and cell types. Activating ligand for the receptor tyrosine kinase MET by binding to it and promoting its dimerization.
Gene Name:
HGF
Uniprot ID:
P14210
Molecular Weight:
83133.115 Da
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Vascular endothelial growth factor receptor binding
Specific Function:
Growth factor active in angiogenesis, vasculogenesis and endothelial cell growth. Induces endothelial cell proliferation, promotes cell migration, inhibits apoptosis and induces permeabilization of blood vessels. Binds to the FLT1/VEGFR1 and KDR/VEGFR2 receptors, heparan sulfate and heparin. NRP1/Neuropilin-1 binds isoforms VEGF-165 and VEGF-145. Isoform VEGF165B binds to KDR but does not activ...
Gene Name:
VEGFA
Uniprot ID:
P15692
Molecular Weight:
27042.205 Da
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Interleukin-8 receptor binding
Specific Function:
IL-8 is a chemotactic factor that attracts neutrophils, basophils, and T-cells, but not monocytes. It is also involved in neutrophil activation. It is released from several cell types in response to an inflammatory stimulus. IL-8(6-77) has a 5-10-fold higher activity on neutrophil activation, IL-8(5-77) has increased activity on neutrophil activation and IL-8(7-77) has a higher affinity to rece...
Gene Name:
CXCL8
Uniprot ID:
P10145
Molecular Weight:
11097.98 Da
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Drug created on November 18, 2007 11:24 / Updated on September 16, 2013 17:27