Identification

Name
ABT-510
Accession Number
DB05434
Type
Small Molecule
Groups
Investigational
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
Synonyms
Not Available
External IDs
ABT 510 / ABT-510
Categories
UNII
CRR8E37XOB
CAS number
251579-55-2
Weight
Average: 994.2317
Monoisotopic: 993.633500563
Chemical Formula
C46H83N13O11
InChI Key
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)[[email protected]@H](NC(=O)[[email protected]](NC(=O)[[email protected]@H](NC(=O)CNC(=O)CN(C)C(C)=O)C(C)C)[[email protected]@H](C)CC)[[email protected]@H](C)O)C(=O)N[[email protected]@H]([[email protected]@H](C)CC)C(=O)N[[email protected]@H](CCCN=C(N)N)C(=O)N1CCC[[email protected]]1C(=O)NCC

Pharmacology

Indication

Investigated for use/treatment in lymphoma (unspecified), melanoma, and solid tumors.

Structured Indications
Not Available
Pharmacodynamics
Not Available
Mechanism of action

ABT-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.

TargetActionsOrganism
UFibroblast growth factor 2Not AvailableHuman
UHepatocyte growth factorNot AvailableHuman
UVascular endothelial growth factor ANot AvailableHuman
UInterleukin-8Not 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
Not Available
Food Interactions
Not Available

References

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
PubChem Compound
6918562
PubChem Substance
175427003
ChemSpider
5293759
BindingDB
50165195
ChEMBL
CHEMBL386115
Wikipedia
ABT-510

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableTumors, Solid1
1CompletedTreatmentNeoplasms, Brain1
1, 2CompletedTreatmentHead and Neck Carcinoma1
2CompletedTreatmentMelanoma (Skin)1

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 Solubility0.0426 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 FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
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)

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 peptoid-peptide hybrids. These are compounds containing a peptoid-peptide backbone, which consists alternating amino acid and n-substituted amino acids linked to each other by a peptide bond.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Peptidomimetics
Sub Class
Peptoid-peptide hybrids
Direct Parent
Peptoid-peptide hybrids
Alternative Parents
Isoleucine and derivatives / Valine and derivatives / N-acyl-alpha amino acids and derivatives / Proline and derivatives / Alpha amino acid amides / N-acylpyrrolidines / Pyrrolidinecarboxamides / N-acyl amines / Acetamides / Tertiary carboxylic acid amides
show 10 more
Substituents
Peptoid/peptide hybrid / Isoleucine or derivatives / Valine or derivatives / Proline or derivatives / N-acyl-alpha amino acid or derivatives / Alpha-amino acid amide / N-substituted-alpha-amino acid / Alpha-amino acid or derivatives / N-acylpyrrolidine / Pyrrolidine carboxylic acid or derivatives
show 27 more
Molecular Framework
Aliphatic heteromonocyclic compounds
External Descriptors
Not 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
Uniprot Name
Fibroblast growth factor 2
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 rec...
Gene Name
HGF
Uniprot ID
P14210
Uniprot Name
Hepatocyte growth factor
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...
Gene Name
VEGFA
Uniprot ID
P15692
Uniprot Name
Vascular endothelial growth factor A
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 t...
Gene Name
CXCL8
Uniprot ID
P10145
Uniprot Name
Interleukin-8
Molecular Weight
11097.98 Da

Drug created on November 18, 2007 11:24 / Updated on December 01, 2017 15:36