1223403-58-4 Usage
Uses
Used in Oncology:
LOXO-101 is used as an antineoplastic agent for the treatment of adult and pediatric patients with solid tumors that have the NTRK gene fusion. It is particularly effective against tumors that overexpress TRKs, as it prevents TRK activation, leading to the induction of cellular apoptosis and the inhibition of cell growth.
Used in Drug Development:
LOXO-101 is also being studied for its potential use in the treatment of other types of cancer. Its high selectivity and potency make it a promising candidate for further research and development in the field of oncology.
Used in Preclinical Research:
In preclinical studies, LOXO-101 has demonstrated its effectiveness in inhibiting the growth of various patient-derived cancer cell lines, such as CUTO-3.29, KM12, and MO-91, with low IC50 values. Additionally, in vivo studies have shown that LOXO-101 (at doses of 60 and 200 mg/kg) significantly reduces tumor growth in a KM12 mouse xenograft model, further supporting its potential as a therapeutic agent in cancer treatment.
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 academic research and scientific papers
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.
Synthesis method of Larotrectinib intermediate and Larotrectinib
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, (2019/02/27)
The invention discloses a synthesis method of Larotrectinib and a Larotrectinib intermediate. N-Boc pyrrolidone and 2,5-difluorophenyl magnesium bromide serve as raw materials, an intermediate A-1 isprepared, the intermediate A-1 is subjected to chiral catalysis hydrogenation, cyclization or first cyclization and afterwards chiral catalysis hydrogenation to obtain a chiral pyrrodlidine intermediate A-4, the intermediate A-4 and an intermediate B-3 are condensed to obtain an intermediate AB-1, the intermediate AB-1 is reduced to obtain an intermediate AB-2, the AB-2 is acylated to obtain an intermediate AB-3, and the AB-3 is subjected to a substitution reaction to obtain the target product Larotrectinib (AB-4). The intermediate A-4 with a high yield and high chiral purity is obtained through a chiral catalysis method, the B-3 with a high yield is obtained through a solvent-free one-pot method, and the Larotrectinib (AB-4) with a high yield and high purity is obtained. According to themethod, the reaction condition can also be applied to large-scale preparation, the method is suitable for industrial production, and therefore, the method has high practical values and social and economic benefits.
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.
SUBSTITUTED PYRAZOLO[1,5-a]PYRIMIDINE COMPOUNDS AS TRK KINASE INHIBITORS
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Page/Page column 59, (2010/05/13)
Compounds of Formula (I) in which R1, R2, R3, R4, X, Y and n have the meanings given in the specification, are inhibitors of Trk kinases and are useful in the treatment of diseases which can be treated with a Trk kinase inhibitor.
![(R)-5-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-amine](/Databaselist/images/loading.webp)
