compound 5e [PMID: 28580438]   Click here for help

GtoPdb Ligand ID: 9712

Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: Compound 5e is a potent FMS-like tyrosine kinase 3 (FLT3, a type III receptor tyrosine kinase) inhibitor that is in preclinical evaluation for the treatment of acute myelogenous leukemia (AML) [3].
Click here for help

Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

✖

View interactive charts of activity data across species
2D Structure
Click here for help

2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

✖
Click here for structure editor
Physico-chemical Properties
Click here for help

Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

✖
Hydrogen bond acceptors 5
Hydrogen bond donors 2
Rotatable bonds 5
Topological polar surface area 62.73
Molecular weight 305.16
XLogP 3.61
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
Click here for help

SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

✖
Canonical SMILES CC(Nc1ccnc(n1)Nc1cccc(c1)c1cccnc1)C
Isomeric SMILES CC(Nc1ccnc(n1)Nc1cccc(c1)c1cccnc1)C
InChI InChI=1S/C18H19N5/c1-13(2)21-17-8-10-20-18(23-17)22-16-7-3-5-14(11-16)15-6-4-9-19-12-15/h3-13H,1-2H3,(H2,20,21,22,23)
InChI Key JTFUPGNZUPRHCZ-UHFFFAOYSA-N
References
1. Gilliland DG, Griffin JD. (2002)
The roles of FLT3 in hematopoiesis and leukemia.
Blood, 100 (5): 1532-42. [PMID:12176867]
2. Hayakawa F, Towatari M, Kiyoi H, Tanimoto M, Kitamura T, Saito H, Naoe T. (2000)
Tandem-duplicated Flt3 constitutively activates STAT5 and MAP kinase and introduces autonomous cell growth in IL-3-dependent cell lines.
Oncogene, 19 (5): 624-31. [PMID:10698507]
3. Jarusiewicz JA, Jeon JY, Connelly MC, Chen Y, Yang L, Baker SD, Guy RK. (2017)
Discovery of a Diaminopyrimidine FLT3 Inhibitor Active against Acute Myeloid Leukemia.
ACS Omega, 2 (5): 1985-2009. [PMID:28580438]
4. Lagunas-Rangel FA, Chávez-Valencia V. (2017)
FLT3-ITD and its current role in acute myeloid leukaemia.
Med Oncol, 34 (6): 114. [PMID:28470536]
5. Mizuki M, Fenski R, Halfter H, Matsumura I, Schmidt R, Müller C, Grüning W, Kratz-Albers K, Serve S, Steur C et al.. (2000)
Flt3 mutations from patients with acute myeloid leukemia induce transformation of 32D cells mediated by the Ras and STAT5 pathways.
Blood, 96 (12): 3907-14. [PMID:11090077]
6. Naoe T, Kiyoi H. (2004)
Normal and oncogenic FLT3.
Cell Mol Life Sci, 61 (23): 2932-8. [PMID:15583855]
7. Yokota S, Kiyoi H, Nakao M, Iwai T, Misawa S, Okuda T, Sonoda Y, Abe T, Kahsima K, Matsuo Y et al.. (1997)
Internal tandem duplication of the FLT3 gene is preferentially seen in acute myeloid leukemia and myelodysplastic syndrome among various hematological malignancies. A study on a large series of patients and cell lines.
Leukemia, 11 (10): 1605-9. [PMID:9324277]