LOXO-101
Modify Date: 2024-01-02 16:04:52
LOXO-101 structure
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Common Name | LOXO-101 | ||
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| CAS Number | 1223403-58-4 | Molecular Weight | 428.435 | |
| Density | 1.6±0.1 g/cm3 | Boiling Point | N/A | |
| Molecular Formula | C21H22F2N6O2 | Melting Point | N/A | |
| MSDS | N/A | Flash Point | N/A | |
Use of LOXO-101Larotrectinib (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). |
| Name | (S)-N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide |
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| Synonym | More Synonyms |
| 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). |
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| Related Catalog | |
| Target |
TrkA TrkB TrkC |
| In Vitro | Larotrectinib (LOXO-101) is an ATP-competitive oral inhibitor of the tropomyosin-related kinase (TRK) family of receptor kinases (TRKA, B, and C), with low nanomolar 50% inhibitory concentrations against all three isoforms, and 1,000-fold or greater selectivity relative to other kinases[1][2]. Measurement of proliferation following treatment with Larotrectinib (LOXO-101) demonstrates a dose-dependent inhibition of cell proliferation in all three cell lines. The IC50 is less than 100 nM for CUTO-3.29 and less than 10 nM for KM12 and MO-91 consistent with the known potency of this drug for the TRK kinase family[3]. |
| In Vivo | In rat and monkey studies, Larotrectinib (LOXO-101) demonstrates 33-100% oral bioavailability and 60-65% plasma protein binding. It has low brain penetration, and is well tolerated in 28 day (d) GLP toxicology studies. A single dose (30 mg/kg) of Larotrectinib (LOXO-101) reduces tyrosine phosphorylation of TRKA and downstream signal transduction (pERK) in the tumor >80%[1]. Athymic nude mice injected with KM12 cells are treated with Larotrectinib (LOXO-101) orally daily for 2 weeks. Dose-dependent tumor inhibition is observed demonstrating the ability of this selective compound to inhibit tumor growth in vivo[4]. Larotrectinib (LOXO-101) (200mg/kg/day p.o for six weeks) reduces leukemic infiltration to undetectable levels in the bone marrow and spleen compared to vehicle-treated mice. Mice treated with Larotrectinib (LOXO-101) are still alive and leukemia-free four weeks after the cessation of treatment, as determined by Xenogen imaging[5]. |
| Animal Admin | Mice[4] Athymic nude mice are used throughout the study. 5×105 KM12 cells are injected subcutaneously into the dorsal flank area of the mice. Tumor volume is monitored by direct measurement with calipers and calculated by the formula: length × (width2)/2. Following the establishment of tumor and when the tumor size is between 150-200 mm2, mice are randomly selected to receive diluent, 60 mg/kg/dose or 200 mg/kg/dose of Larotrectinib (LOXO-101). Larotrectinib (LOXO-101) is administered by oral gavage once daily for 14 days. After the last dose, tissue and blood are collected at 3, 6 and 24 hours post-treatment[4]. |
| References |
[1]. Karyn Bouhana, et al. LOXO-101, a pan TRK inhibitor, For The Treatment Of TRK-driven Cancers. |
| Density | 1.6±0.1 g/cm3 |
|---|---|
| Molecular Formula | C21H22F2N6O2 |
| Molecular Weight | 428.435 |
| Exact Mass | 428.177216 |
| LogP | 1.48 |
| Index of Refraction | 1.725 |
| Storage condition | -20℃ |
| LOXO-101 |
| Larotrectinib |
| UNII:PF9462I9HX |
| (3S)-N-{5-[(2R)-2-(2,5-Difluorophenyl)-1-pyrrolidinyl]pyrazolo[1,5-a]pyrimidin-3-yl}-3-hydroxy-1-pyrrolidinecarboxamide |
| MFCD28902192 |
| 1-Pyrrolidinecarboxamide, N-[5-[(2R)-2-(2,5-difluorophenyl)-1-pyrrolidinyl]pyrazolo[1,5-a]pyrimidin-3-yl]-3-hydroxy-, (3S)- |