Description
Key facts
CAS number:1223403-58-4,
Purity:>98%,
Form:SolidSee storage information,
Molecular weight:428.4 Da,
Molecular formula:C21H22F2N6O2,
PubChem:46188928,
Nature:Synthetic,
Solubility:Soluble in DMSO to 10 mM,
Biochemical name:Larotrectinib,
Biological description:Potent, ATP-competitive TRK inhibitor with IC₅₀s in low nanomolar range for inhibition of all TRK family members in binding and cellular assays, with 100-fold selectivity over other kinases, with 2 to 20 nM cellular potency against the TRKA, TRKB, and TRKC kinases.,
Canonical smiles:C1CC(N(C1)C2=NC3=C(C=NN3C=C2)NC(=O)N4CCC(C4)O)C5=C(C=CC(=C5)F)F,
Isomeric smiles:C1C[C@@H](N(C1)C2=NC3=C(C=NN3C=C2)NC(=O)N4CC[C@@H](C4)O)C5=C(C=CC(=C5)F)F,
InChi:InChI=1S/C21H22F2N6O2/c22-13-3-4-16(23)15(10-13)18-2-1-7-28(18)19-6-9-29-20(26-19)17(11-24-29)25-21(31)27-8-5-14(30)12-27/h3-4,6,9-11,14,18,30H,1-2,5,7-8,12H2,(H,25,31)/t14-,18+/m0/s1,
InChiKey:NYNZQNWKBKUAII-KBXCAEBGSA-N,
IUPAC Name:(3S)-N-[5-[(2R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]-3-hydroxypyrrolidine-1-carboxamide
Product details:
This product is manufactured by BioVision, an Abcam company and was previously called B2291 LOXO-101. B2291-5 is the same size as the 5 mg size of ab286990.
Properties and Storage Information:
Shipped at conditions-Blue Ice, Appropriate short-term storage conditions--20°C, Appropriate long-term storage conditions--20°C, Storage information-Store in the dark, This product is air and light sensitive and impurities can occur as a result of air oxidation or due to metabolism by microbes
Supplementary Information:
This supplementary information is collated from multiple sources and compiled automatically.
TrkA TrkB and TrkC also known as NTRK1 NTRK2 and NTRK3 respectively are tropomyosin receptor kinases. These proteins are transmembrane receptors containing extracellular ligand-binding domains a single transmembrane helix and an intracellular kinase domain. TrkA has a mass of about 140 kDa TrkB around 145 kDa and TrkC approximately 143 kDa. Expression of these receptors occurs mainly in the nervous system but they are also present in other tissues like the heart and pancreas. Each receptor exhibits selectivity for different neurotrophins with TrkA binding to nerve growth factor (NGF) TrkB binding to brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT-4) and TrkC recognizing neurotrophin-3 (NT-3).
Biological function summary
These Trk receptors play essential roles in the development of the nervous system. Upon binding their specific ligands Trk receptors undergo dimerization and autophosphorylation on key tyrosine residues. This phosphorylation activates downstream signaling cascades that promote neuron survival differentiation and axonal growth. The receptors are not part of a larger complex but they interact with adaptor proteins that link them to intracellular signaling pathways. These interactions enhance cellular processes like synaptic plasticity and memory formation.
Pathways
TrkA TrkB and TrkC are central to the MAPK/ERK and PI3K/AKT pathways. Activation of these pathways leads to neuronal survival and growth mediated by proteins like Ras and PI3K. These pathways highlight the connection of Trk receptors with other important signaling proteins such as Shc and PLCγ. Through these pathways they also contribute to cellular responses that influence nerve cell communication and survival under stress conditions.
Mutations or dysregulation of Trk receptors implicate them in several neurodegenerative disorders and cancers. Neurodegenerative conditions like Alzheimer's disease show altered Trk signaling while certain cancers including neuroblastoma involve TrkA mutations or amplifications. TrkB dysregulation is associated with mood disorders and obesity also interacting with BDNF in these conditions. Pathologically the relationship with connected proteins such as BDNF in TrkB-related pathways appears important in understanding these diseases.
