General
Preferred name
GNF-5837
Synonyms
GNF 5837 ()
compound 22 ()
P&D ID
PD012859
CAS
1033769-28-6
Tags
available
probe
drug candidate
Drug indication
Discovery agent
Probe info
Probe type
experimental probe
Probe sources
Probe targets
[[ compound.targets[t].gene_name ]]
Probe control
Probe control not defined
Orthogonal probes
10
No orthogonal probes found
Similar probes
0
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
DESCRIPTION
GNF-5837 is an investigational, selective, and orally bioavailable inhibitor of the neurotrophic receptor tyrosine kinases TrkA, TrkB and TrkC . This compound is a useful tool for the investigation of TRK biology in human diseases.
(GtoPdb)
COMMENT
There are more well-characterized tools, in particular Laratrectinib which is both approved for human use and better profiled for selectivity against more kinases (link)or perhaps clinical compounds AZD7451. Cell Concentration notes: Fig1 of the 2nd reference shows a plateau of activity from 50-500 nM in GOT1 cell. Ref1 demonstrates sufficient IV and PO exposure for human tumor xenograft studies plus demonstrated efficacy. However, given the ~86% similarity between human and rat/mouse TRKA, I would recommend confirming rat or mouse potency comparable to humans before using rats or mice as an efficacy model in a non-human xenograft study Aug 4 2021 - 9:23pm; Together the two reference documents provide acceptable evidence that cell-based and organism-based anticancer activity may be due to pan TRK inhibition, and the E-R Cancer study shows evidence of target inhibition in cells. However, like many kinase inhibitor studies, more evidence may be required to be certain that in vivo efficacy reflects target engagement and further, also like many kinase inhibitor studies, in the absence of an entirely comprehensive kinase profile and other profiling (including tubulin for example), some caution is still advised in assuming that all cell-based activity arises from pan Trk inhibition since the kinase inhibitor field continues to surprise. Finally, it would be useful to identify a negative control – perhaps an N-methylated analogue or better, one with the CF3 moved to the para position (if all Trk activity is lost), and to use this in all studies. Aug 26 2021 - 9:13am
DESCRIPTION
GNF-5837 is a potent, selective, and orally bioavailable pan-tropomyosin receptor kinase (TRK) inhibitor which display antiproliferative effects in cellular Ba/F3 assays ( IC50 values of 7 nM, 9 nM and 11 nM for cells containing the fusion proteins Tel-TrkC, Tel-TrkB and Tel-TrkA, respectively) [1].
PRICE
79
MOA
Inhibitor
(Chemical Probes.org)
DESCRIPTION
Potent Trk inhibitor; inhibits TrkA, TrkB and TrkC
(Tocriscreen Plus)
DESCRIPTION
DNA topoisomerase I inhibitor; Camptothecin (Cat. No. 1100) analog
(Tocris Bioactive Compound Library)
DESCRIPTION
GNF-5837 is a specific, and orally bioavailable pan-TRK inhibitor for TrkA/TrkB (IC50: 8/12 nM).
(TargetMol Bioactive Compound Library)
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Compound Sets
24
AdooQ Bioactive Compound Library
Axon Medchem Screening Library
Cayman Chemical Bioactives
Chemical Probes.org
Concise Guide to Pharmacology 2017/18
Concise Guide to Pharmacology 2019/20
Concise Guide to Pharmacology 2021/22
Concise Guide to Pharmacology 2023/24
CZ-OPENSCREEN Bioactive Library
Drug Repurposing Hub
DrugMAP
EU-OPENSCREEN Bioactive Compound Library
EUbOPEN Chemogenomics Library
Guide to Pharmacology
High-quality chemical probes
JUMP-Target 1 Compound Set
LINCS compound set
Mcule NIBR MoA Box Subset
MedChem Express Bioactive Compound Library
Novartis Chemogenetic Library (NIBR MoA Box)
Selleckchem Bioactive Compound Library
TargetMol Bioactive Compound Library
Tocris Bioactive Compound Library
Tocriscreen Plus
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
13
Molecular Weight
535.16
Hydrogen Bond Acceptors
3
Hydrogen Bond Donors
5
Rotatable Bonds
5
Ring Count
5
Aromatic Ring Count
4
cLogP
7.36
TPSA
98.05
Fraction CSP3
0.07
Chiral centers
0.0
Largest ring
6.0
QED
0.14
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Target Type
Enzyme-Linked Receptors
Target
KIT
PDGFRβ
Trk Receptor
TrkA
TrkB
TrkC
NTRK1, NTRK2, NTRK3
Trk inhibitor
TRKA, TRKB, TRKC
NTRK1
Primary Target
Trk Receptors
MOA
Inhibitor
NTRK1 gene inhibitor
growth factor receptor inhibitor
Member status
member
Pathway
Angiogenesis
Tyrosine Kinase/Adaptors
Neuronal Signaling
Protein Tyrosine Kinase/RTK
Target subclass
TK
TK, TK, TK
Target class
Protein kinase
Kinase, Kinase, Kinase
Recommended Cell Concentration
100 nM
Source data
