General
Preferred name
larotrectinib
Synonyms
LOXO-101 ()
ARRY-470 ()
ARRY-470 (sulfate) ()
LOXO-101 sulfate ()
LOXO-101 (sulfate) ()
ARRY-470 (sulfate)LOXO-101 (sulfate)Larotrectinib (LOXO-101) sulfate ()
LOXO-101 (ARRY-470) ()
LAROTRECTINIB SULFATE ()
LOXO-101LOXO 101LOXO101A-9048 ()
BAY-2757556 ()
BAY2757556 ()
Larotrectinib (LOXO-101) sulfate ()
ARRY-470, Larotrectinib ()
Vitrakvi, LOXO-101, ARRY-470 ()
Vitrakvi ()
ARRY-470 SULFATE ()
P&D ID
PD049151
CAS
1223403-58-4
1223405-08-0
Tags
available
probe
drug
Approved by
EMA
FDA
PMDA
First approval
2018
Drug indication
Neoplasm
Solid tumour/cancer
Drug Status
investigational
approved
Max Phase
4.0
Probe info
Probe type
experimental probe
P&D approved
Probe sources
Probe targets
[[ compound.targets[t].gene_name ]]
Probe control
Probe control not defined
Orthogonal probes
2
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
Larotrectinib (LOXO-101) is an orally available, potent and selective inhibitor of the receptor tyrosine kinases of the TRK family . In these referenced patents, data is provided for inhibition of neurotrophic tyrosine kinase, receptor, type 1 (NTRK1, a.k.a. TrkA) .
(GtoPdb)
INDICATION
Larotrectinib is a tyrosine kinase inhibitor that is currently indicated for the treatment of adult and pediatric patients with solid tumors that either a) have a neurotrophic receptor tyrosine kinase (NTRK) gene fusion without a known acquired resistance mutation, b) are metastatic or where surgical resection is likely to result in severe morbidity, and c) have no satisfactory alternative treatments or that have progressed following treatment [FDA Label].; ; At the moment, these uses of larotrectinib are only approved under the auspices of an accelerated approval by the US FDA based on overall response rate and duration of response and continuation of support for these indications may be contingent upon the verification and description of continued clinical benefit in confirmatory trials [FDA Label].
ABSORPTION
The mean absolute bioavailability of larotrectinib capsules has been recorded as 34%, from a range spanning 32% to 37% [FDA Label]. In adult patients who received larotrectinib capsules 100 mg twice daily, peak plasma levels Cmax were achieved at about one hour after dosing and steady-state was reached within the time span of three days [FDA Label]. The mean steady-state of these administered larotrectinib capsules was Cmax 788 ng/mL and the AUC(0-24hr) was 4351 ng*h/mL [FDA Label]. Concurrently, in healthy subjects, the AUC of the administered larotrectinib oral solution formulation was similar to that of the capsules and the particular Cmax was 36% greater with the oral solution [FDA Label].; ; The AUC of larotrectinib was similar but the Cmax was reduced by 35% after oral administration of a single 100 mg capsule of larotrectinib to healthy subjects taken with a high-fat meal (approximately 900 calories, 58 grams carbohydrate, 56 grams fat and 43 grams protein) compared to the Cmax and AUC in the fasted state [FDA Label].
MOA
Tropomysoin Receptor Kinases (TRK) like TRKA, TRKB, and TRKC elicit activities that regulate the natural growth, differentiation, and survival of neurons when they interact with endogenous neutrotrophin ligands [A40035, A40037, A40038, A40046, A40047]. TRKA, TRKB, and TRKC are themselves encoded by the NTRK1, NTRK2, and NTRK3 genes, respectively [A40035, A40037, A40038, A40046, A40047]. It has been discovered that chromosomal rearrangements involving in-frame fusions of these genes with various partners, translocations in the TRK kinase domains, mutations in the TRK ligand-binding site, amplifications of NTRK, or the expression of TRK splice variants can result in constitutively-activated chimeric TRK fusion proteins that can act as oncogenic drivers that promote cell proliferation and survival in tumor cell lines [A40035, A40037, A40038, A40046, A40047, FDA Label].; ; Subsequently, larotrectinib functions as an inhibitor of TRKs including TRKA, B, and C [A40035, A40037, A40038, A40046, A40047, FDA Label]. In in vitro and in vivo tumor models, larotrectinib demonstrated anti-tumor activity in cells with constitutive activation of TRK proteins resulting from gene fusions, deletion of a protein regulatory domain, or in cells with TRK protein overexpression [A40035, A40037, A40038, A40046, A40047, FDA Label]. Larotrectinib had minimal activity in cell lines with point mutations in the TRKA kinase domain, including the clinically identified acquired resistance mutation, G595R [FDA Label]. Point mutations in the TRKC kinase domain with clinically identified acquired resistance to larotrectinib include G623R, G696A, and F617L [FDA Label].
DESCRIPTION
Larotrectinib (LOXO-101) is an ATP-competitive oral, selective inhibitor of the tropomyosin-related kinase (TRK) family receptors, with low nanomolar 50% inhibitory concentrations against all three isoforms (TRKA, B, and C).
PRICE
89
DESCRIPTION
Larotrectinib sulfate (LOXO-101 sulfate; ARRY-470 sulfate) is an ATP-competitive oral, selective inhibitor of the tropomyosin-related kinase (TRK) family receptors, with low nanomolar 50% inhibitory concentrations against all three isoforms (TRKA, B, and C).
PRICE
86
MOA
Inhibitor
(Chemical Probes.org)
DESCRIPTION
On november 26, 2018, the FDA approved larotrectinib to treat patients whose cancers have a specific genetic feature (biomarker)
(PKIDB)
DESCRIPTION
LOXO-101, also known as ARRY-470, is an orally bioavailable, potent, ATP-competitive inhibitor of TRKA, TRKB, and TRKC. LOXO-101 has IC50 values in the low nanomolar range for inhibition of all three TRK family members in binding and cellular assays, with 100x selectivity over other kinases, and has shown acceptable pharmaceutical properties and safety in nonclinical models.
(BOC Sciences Bioactive Compounds)
DESCRIPTION
Larotrectinib (LOXO-101) is an orally administered inhibitor of the TRK kinase, demonstrating high selectivity exclusively for the TRK family of receptors (IC50s = 2-20 nM).
(TargetMol Bioactive Compound Library)
DESCRIPTION
Larotrectinib sulfate (LOXO-101 sulfate) is an oral active and specific ATP-competitive inhibitor of tropomyosin receptor kinases (TRK).
(TargetMol Bioactive Compound Library)
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Cell lines
4
Organisms
0
Compound Sets
27
AdooQ Bioactive Compound Library
Axon Medchem Screening Library
BOC Sciences Bioactive Compounds
Cayman Chemical Bioactives
ChEMBL Approved Drugs
ChEMBL Drugs
Chemical Probes.org
CZ-OPENSCREEN Bioactive Library
Drug Repurposing Hub
DrugBank
DrugBank Approved Drugs
DrugCentral
DrugCentral Approved Drugs
DrugMAP
DrugMAP Approved Drugs
EU-OPENSCREEN Bioactive Compound Library
Guide to Pharmacology
High-quality chemical probes
JUMP-Target 1 Compound Set
Mcule NIBR MoA Box Subset
NCATS Inxight Approved Drugs
NIH Approved Oncology Drugs
Novartis Chemogenetic Library (NIBR MoA Box)
PKIDB
Selleckchem Bioactive Compound Library
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
171
Molecular Weight
428.18
Hydrogen Bond Acceptors
6
Hydrogen Bond Donors
2
Rotatable Bonds
3
Ring Count
5
Aromatic Ring Count
3
cLogP
2.95
TPSA
86.0
Fraction CSP3
0.38
Chiral centers
2.0
Largest ring
6.0
QED
0.67
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Target
Apoptosis
TRK
Trk Receptor
NTRK1, NTRK2, NTRK3
Trk inhibitor
NTRK1
NTRK2
NTRK3
Apoptosis related,Trk receptor
Member status
member
MOA
Inhibitor of TRK
tropomyosin receptor kinase inhibitor
Pathway
Neuronal Signaling
Protein Tyrosine Kinase/RTK
Tyrosine Kinase/Adaptors
Solubility
Soluble in DMSO, not in water
Target class
Kinase, Kinase, Kinase
Target subclass
Tyr kinase, Tyr kinase, Tyr kinase
Source data
