1223403-58-4 Usage
Description
Different sources of media describe the Description of 1223403-58-4 differently. You can refer to the following data:
1. Larotrectinib (VITRAKVIR) is an orally administered, small molecule, highly-selective, tropomyosin receptor kinase (TRK) inhibitor that was developed by Loxo Oncology in collaboration with Bayer AG as a treatment for adult and paediatric patients whose cancers harbour neurotrophic receptor tyrosine kinase (NTRK) gene fusions.?
Larotrectinib is a highly selective, potent inhibitor of TRKA, TRKB and TRKC (in vitro 50% inhibitory constant 5–11 nmol/L), with minimal or no activity against other kinase and non-kinase targets [1, 2]. Inhibition of TRKs prevents TRK activation, resulting in both the induction of cellular apoptosis and the inhibition of cell growth in tumours that overexpress TRKs.
2. LOXO-101 is an inhibitor of the tropomyosin-related kinases TrkA, TrkB, and TrkC (IC50s = 2-20 nM). It is selective for TrkA, -B, and -C over a panel of 226 kinases at 1 μM. LOXO-101 inhibits the growth of CUTO-3.29, KM12, and MO-91 patient-derived cancer cell lines (IC50s = <100, <10, and <10 nM, respectively). In vivo, LOXO-101 (60 and 200 mg/kg) reduces tumor growth in a KM12 mouse xenograft model.
Uses
Different sources of media describe the Uses of 1223403-58-4 differently. You can refer to the following data:
1. LOXO-101 is a drug used to treat adults and children with certain types of solid tumors that have spread or cannot be removed by surgery and have the?NTRK?gene fusion. It is also being studied in the treatment of other types of cancer.
2. Larotrectinib is a TRK Inhibitor (Tyrosine kinase inhibitor).
Application status
LOXO-101 was the first drug to be specifically developed and approved to treat?any?cancer containing certain mutations, as opposed to cancers of specific tissues (i.e., the approval is "tissue agnostic"). Several earlier drugs, including?pembrolizumab, were eventually approved by the FDA for treatment of specific mutations independent of the type of cancer, but those drugs had been initially developed for specific cancer types.The U.S.?Food and Drug Administration?(FDA) considers it to be a?first-in-class medication.Phase II clinical trials evaluating the drug for efficacy and safety in treating several types of solid tumors are ongoing.[12]Larotrectinib was approved for medical use in the European Union in September 2019.[13][14]?It was approved for medical use in Australia in August 2020.
References
1) Ghilardi?et al.?(2010),?Administration of a tropomyosin receptor kinase inhibitor attenuates sarcoma-induced nerve sprouting, neuroma formation, and bone cancer pain; Mol. Pain,?6?87
2) Doebele?et al.?(2015),?An Oncogenic NTRK Fusion in a Patient with Soft-Tissue Sarcoma with Response to the Tropomyosin-Related Kinase Inhibitor LOXO-101; Cancer Discov.,?5?1049
3) Landman?et al.?(2018),?Rapid response to Larotrectinib (LOXO-101) in Adult Chemotherapy-Na?ve Patients With Advanced Triple-Negative Secretory Breast Cancer Expressing ETV6-NTRK3 Fusion; Clin. Breast Cancer,?18?e267
4) Drilon?et al.?(2018),?Efficacy of Larotrectinib in TRK Fusion-Positive Cancers in Adults and Children; N. Engl. J. Med.,?378?731
Check Digit Verification of cas no
The CAS Registry Mumber 1223403-58-4 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,2,2,3,4,0 and 3 respectively; the second part has 2 digits, 5 and 8 respectively.
Calculate Digit Verification of CAS Registry Number 1223403-58:
(9*1)+(8*2)+(7*2)+(6*3)+(5*4)+(4*0)+(3*3)+(2*5)+(1*8)=104
104 % 10 = 4
So 1223403-58-4 is a valid CAS Registry Number.
1223403-58-4Relevant articles and documents
Preparation method of broad-spectrum tumor drug lalotinib
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, (2021/08/28)
The invention relates to a preparation method of lalotinib. According to the method, a compound in a formula II is selectively reduced to obtain a compound in a formula I. The invention provides the novel preparation method of lalotinib, and the method has the advantages of mild reaction conditions, high chiral selectivity and high product yield, and is suitable for commercial production.
Preparation method of Larotrectinib and intermediate of Larotrectinib
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Paragraph 0027, (2018/05/16)
The invention relates to the field of pharmaceutical chemistry, and specifically relates to a preparation method of Larotrectinib and an intermediate of Larotrectinib. According to the method, 5-chloro-3-nitropyrazolo[1,5-a]pyrimidine is taken as a raw material, a compound shown as the formula 5 in the description is obtained through a three-step reaction, a substitution reaction occurs between the compound shown as the formula 5 and a compound shown as the formula 6 in the description so as to obtain Larotrectinib. The method provides a new synthetic route of Larotrectinib, the consumption ofthe compound shown as the formula 6 is reduced, the production cost is reduced, and the reaction condition is mild, no column chromatography purification is needed, and is suitable for industrial production.
