Golotimod

Identification

Name
Golotimod
Accession Number
DB05475
Type
Small Molecule
Groups
Investigational
Description

SCV-07 (g -D-glutamyl-L-tryptophan) is a novel synthetic dipeptide that acts broadly on the Toll-like receptor pathway. It has been shown to stimulate T-lymphocyte differentiation, macrocytic phagocytosis, and specific immune responses, and enhance IL-2 and INF-g production. Due to this preferential activation of Th1 cytokine production, SCV-07 may show utility in treatment of tuberculosis. It can be administered orally or subcutaneously. In independent studies, treatment of tuberculosis with SCV-07 improved clearance of mycobacteria, improved cavity healing, improvements in immune parameters and reduced symptoms (fever, weakness, sweating, dry cough, productive cough, dyspnea, chest pain, tachycardia) without any adverse local or general effects. SCV-07 has shown efficacy in treating various viral and bacterial infections.

Structure
Thumb
Synonyms
Not Available
External IDs
SCV-07
Categories
UNII
637C487Y09
CAS number
229305-39-9
Weight
Average: 333.3392
Monoisotopic: 333.132470733
Chemical Formula
C16H19N3O5
InChI Key
CATMPQFFVNKDEY-YPMHNXCESA-N
InChI
InChI=1S/C16H19N3O5/c17-11(15(21)22)5-6-14(20)19-13(16(23)24)7-9-8-18-12-4-2-1-3-10(9)12/h1-4,8,11,13,18H,5-7,17H2,(H,19,20)(H,21,22)(H,23,24)/t11-,13+/m1/s1
IUPAC Name
(2R)-2-amino-4-{[(1S)-1-carboxy-2-(1H-indol-3-yl)ethyl]carbamoyl}butanoic acid
SMILES
N[[email protected]](CCC(=O)N[[email protected]@H](CC1=CNC2=CC=CC=C12)C(O)=O)C(O)=O

Pharmacology

Indication

Investigated for use/treatment in hepatitis (viral, C), infectious and parasitic disease (unspecified), and tuberculosis.

Structured Indications
Not Available
Pharmacodynamics

SCV-07 (g -D-glutamyl-L-tryptophan) is a novel synthetic dipeptide that acts broadly on the Toll-like receptor pathway. It has been shown to stimulate T-lymphocyte differentiation, macrocytic phagocytosis, and specific immune responses, and enhance IL-2 and INF-g production.

Mechanism of action

SCV-07 (g -D-glutamyl-L-tryptophan) has broad effects on the Toll-like receptor (TLR) pathway.

TargetActionsOrganism
UToll-like receptor 2Not AvailableHuman
UToll-like receptor 4Not AvailableHuman
UToll-like receptor 7Not AvailableHuman
UToll-like receptor 9Not 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

No adverse effects were observed in any patients participating in clinical trials.

Affected organisms
  • Hepatitis C virus, RSV and other RNA/DNA viruses
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. Aspinall RJ, Pockros PJ: SCV-07 (SciClone Pharmaceuticals/Verta). Curr Opin Investig Drugs. 2006 Feb;7(2):180-5. [PubMed:16499289]
  2. Suzuki H, Kato K, Kumagai H: Development of an efficient enzymatic production of gamma-D-glutamyl-L-tryptophan (SCV-07), a prospective medicine for tuberculosis, with bacterial gamma-glutamyltranspeptidase. J Biotechnol. 2004 Aug 5;111(3):291-5. [PubMed:15246665]
  3. Bayes M, Rabasseda X, Prous JR: Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2003 Jun;25(5):387-408. [PubMed:12851663]
  4. Orellana C: Immune system stimulator shows promise against tuberculosis. Lancet Infect Dis. 2002 Dec;2(12):711. [PubMed:12467673]
External Links
PubChem Compound
6992140
PubChem Substance
175427014
ChemSpider
5360288
ChEMBL
CHEMBL2103812

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedHealth Services ResearchChronic Hepatitis C Virus (HCV) Infection1
2CompletedHealth Services ResearchHead and Neck Carcinoma / Oral Mucositis1
2Unknown StatusPreventionOral Mucositis1
Not AvailableCompletedNot AvailableChronic Hepatitis C Virus (HCV) Infection1

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 Solubility0.347 mg/mLALOGPS
logP-1.4ALOGPS
logP-2ChemAxon
logS-3ALOGPS
pKa (Strongest Acidic)1.98ChemAxon
pKa (Strongest Basic)9.31ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count5ChemAxon
Polar Surface Area145.51 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity84.29 m3·mol-1ChemAxon
Polarizability33.36 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.824
Blood Brain Barrier+0.8532
Caco-2 permeable-0.8369
P-glycoprotein substrateNon-substrate0.605
P-glycoprotein inhibitor INon-inhibitor0.9875
P-glycoprotein inhibitor IINon-inhibitor0.9811
Renal organic cation transporterNon-inhibitor0.9088
CYP450 2C9 substrateNon-substrate0.8633
CYP450 2D6 substrateNon-substrate0.8422
CYP450 3A4 substrateNon-substrate0.6654
CYP450 1A2 substrateNon-inhibitor0.9522
CYP450 2C9 inhibitorNon-inhibitor0.9458
CYP450 2D6 inhibitorNon-inhibitor0.9427
CYP450 2C19 inhibitorNon-inhibitor0.9514
CYP450 3A4 inhibitorNon-inhibitor0.9435
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9788
Ames testNon AMES toxic0.9305
CarcinogenicityNon-carcinogens0.9641
BiodegradationNot ready biodegradable0.7093
Rat acute toxicity1.6624 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9896
hERG inhibition (predictor II)Non-inhibitor0.9498
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 dipeptides. These are organic compounds containing a sequence of exactly two alpha-amino acids joined by a peptide bond.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Dipeptides
Alternative Parents
Gamma-glutamyl amino acids / Glutamine and derivatives / N-acyl-L-alpha-amino acids / 3-alkylindoles / D-alpha-amino acids / Substituted pyrroles / Benzenoids / Dicarboxylic acids and derivatives / N-acyl amines / Heteroaromatic compounds
show 9 more
Substituents
Alpha-dipeptide / Gamma-glutamyl alpha-amino acid / Glutamine or derivatives / N-acyl-alpha amino acid or derivatives / N-acyl-alpha-amino acid / N-acyl-l-alpha-amino acid / Alpha-amino acid / 3-alkylindole / D-alpha-amino acid / Alpha-amino acid or derivatives
show 29 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Triacyl lipopeptide binding
Specific Function
Cooperates with LY96 to mediate the innate immune response to bacterial lipoproteins and other microbial cell wall components. Cooperates with TLR1 or TLR6 to mediate the innate immune response to ...
Gene Name
TLR2
Uniprot ID
O60603
Uniprot Name
Toll-like receptor 2
Molecular Weight
89836.575 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Transmembrane signaling receptor activity
Specific Function
Cooperates with LY96 and CD14 to mediate the innate immune response to bacterial lipopolysaccharide (LPS). Acts via MYD88, TIRAP and TRAF6, leading to NF-kappa-B activation, cytokine secretion and ...
Gene Name
TLR4
Uniprot ID
O00206
Uniprot Name
Toll-like receptor 4
Molecular Weight
95679.19 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Transmembrane signaling receptor activity
Specific Function
Key component of innate and adaptive immunity. TLRs (Toll-like receptors) control host immune response against pathogens through recognition of molecular patterns specific to microorganisms. TLR7 i...
Gene Name
TLR7
Uniprot ID
Q9NYK1
Uniprot Name
Toll-like receptor 7
Molecular Weight
120920.8 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Transmembrane signaling receptor activity
Specific Function
Key component of innate and adaptive immunity. TLRs (Toll-like receptors) control host immune response against pathogens through recognition of molecular patterns specific to microorganisms. TLR9 i...
Gene Name
TLR9
Uniprot ID
Q9NR96
Uniprot Name
Toll-like receptor 9
Molecular Weight
115858.665 Da

Drug created on November 18, 2007 11:25 / Updated on December 01, 2017 15:36