CAS 1223405-08-0|LOXO-101 (sulfate)
Introduction：Basic information about CAS 1223405-08-0|LOXO-101 (sulfate), including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
| Common Name | LOXO-101 (sulfate) | ||
|---|---|---|---|
| CAS Number | 1223405-08-0 | Molecular Weight | 526.514 |
| Density | / | Boiling Point | / |
| Molecular Formula | C21H24F2N6O6S | Melting Point | / |
| MSDS | / | Flash Point | / |
Names
| Name | (3S)-N-[5-[(2R)-2-(2,5-Difluorophenyl)-1-pyrrolidinyl]pyrazolo[1,5-a]pyrimidin-3-yl]-3-hydroxy-1-pyrrolidinecarboxamide sulfate (1:1) |
|---|---|
| Synonym | More Synonyms |
LOXO-101 (sulfate) BiologicalActivity
| Description | Larotrectinib (LOXO-101) 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). |
|---|---|
| Related Catalog | Signaling Pathways >>Protein Tyrosine Kinase/RTK >>Trk ReceptorResearch Areas >>Cancer |
| 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 sulfate 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 sulfate 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. [2]. Nagasubramanian R, et al. Infantile Fibrosarcoma With NTRK3-ETV6 Fusion Successfully Treated With the Tropomyosin-Related Kinase Inhibitor LOXO-101. Pediatr Blood Cancer. 2016 Aug;63(8):1468-70. [3]. Doebele RC, et al. An Oncogenic NTRK Fusion in a Patient with Soft-Tissue Sarcoma with Response to the Tropomyosin-Related Kinase Inhibitor LOXO-101. Cancer Discov. 2015 Oct;5(10):1049-57. [4]. Doebele RC, et al. An Oncogenic NTRK Fusion in a Patient with Soft-Tissue Sarcoma with Response to the Tropomyosin-Related Kinase Inhibitor LOXO-101. Cancer Discov. 2015 Oct;5(10):1049-57. [5]. Kathryn G, et al. Genetic Modeling and Therapeutic Targeting of ETV6-NTRK3 with Loxo-101in Acute Lymphoblastic Leukemia. Blood 2016 128:278. |
Chemical & Physical Properties
| Molecular Formula | C21H24F2N6O6S |
|---|---|
| Molecular Weight | 526.514 |
| Exact Mass | 526.144592 |
| PSA | 168.98000 |
| LogP | 3.45140 |
| InChIKey | PXHANKVTFWSDSG-QLOBERJESA-N |
| SMILES | O=C(Nc1cnn2ccc(N3CCCC3c3cc(F)ccc3F)nc12)N1CCC(O)C1.O=S(=O)(O)O |
| Storage condition | 2-8℃ |
Synonyms
| (3S)-N-{5-[(2R)-2-(2,5-Difluorophenyl)-1-pyrrolidinyl]pyrazolo[1,5-a]pyrimidin-3-yl}-3-hydroxy-1-pyrrolidinecarboxamide sulfate (1:1) |
| 1-Pyrrolidinecarboxamide, N-[5-[(2R)-2-(2,5-difluorophenyl)-1-pyrrolidinyl]pyrazolo[1,5-a]pyrimidin-3-yl]-3-hydroxy-, (3S)-, sulfate (1:1) (salt) |
| UNII:RDF76R62ID |
| Larotrectinib sulfate |
| LOXO-101 sulfate |
| LOXO-101 (sulfate) |
