ABT-510

Identification

Generic Name
ABT-510
DrugBank Accession Number
DB05434
Background

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.

Type
Small Molecule
Groups
Investigational
Structure
Thumb
Weight
Average: 994.2317
Monoisotopic: 993.633500563
Chemical Formula
C46H83N13O11
Synonyms
Not Available
External IDs
  • ABT 510
  • ABT-510

Pharmacology

Indication

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

Pharmacology
Reduce drug development failure rates
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Contraindications & Blackbox Warnings
Contraindications
Avoid life-threatening adverse drug events
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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 AvailableHumans
UHepatocyte growth factorNot AvailableHumans
UVascular endothelial growth factor ANot AvailableHumans
UInterleukin-8Not 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
Adverseeffects
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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.
Not Available
Food Interactions
Not Available

Categories

Drug Categories
Chemical TaxonomyProvided by Classyfire
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
Acetamide / Alcohol / Aliphatic heteromonocyclic compound / Alpha-amino acid amide / Alpha-amino acid or derivatives / Azacycle / Carbonyl group / Carboxamide group / Carboximidamide / Carboxylic acid derivative
show 27 more
Molecular Framework
Aliphatic heteromonocyclic compounds
External Descriptors
Not Available
Affected organisms
Not Available

Chemical Identifiers

UNII
CRR8E37XOB
CAS number
251579-55-2
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[C@H](NC(=O)[C@@H](NC(=O)[C@H](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[C@H]1C(=O)NCC

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. [Article]
  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. [Article]
PubChem Compound
6918562
PubChem Substance
175427003
ChemSpider
5293759
BindingDB
50165195
ChEMBL
CHEMBL386115
ZINC
ZINC000169362874
Wikipedia
ABT-510

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentLymphoma, Hodgkins / Non-Hodgkin's Lymphoma (NHL)1
2CompletedTreatmentMalignant Melanoma of Skin1
2CompletedTreatmentRenal Cell Adenocarcinoma1
2CompletedTreatmentSoft Tissue Sarcoma (STS)1
2TerminatedTreatmentNon-Small Cell Lung Carcinoma (NSCLC)1
1CompletedNot AvailableTumors, Solid1
1CompletedTreatmentNeoplasms, Brain1
1, 2CompletedTreatmentHead and Neck Carcinoma1

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

Targets

Drugtargets2
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Kind
Protein
Organism
Humans
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
Humans
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
Humans
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
Humans
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 18:24 / Updated on June 12, 2020 16:52