1421373-65-0 Usage
Uses
Different sources of media describe the Uses of 1421373-65-0 differently. You can refer to the following data:
1. AZD-9291 (Osimertinib) is a oral, third generation, small-molecule epidermal growth factor receptor (EGFR) inhibitor and antineoplastic agent. In addition, it is a Cytochrome P450 3A inhibitor, and Cytochrome P450 3A4 Inducer, and Cytochrome P450 1A2 Inducer, and Breast Cancer Resistance Protein Inhibitor. It is used for the treatment of advanced non-small cell lung cancer (NSCLC) where mutant EGFR form (such as T790M) is often presented. Through suppressing the EGFR-mediated signalling, it cause cell death and inhibit tumour growth in related cancer cells.
2. AZD 9291 is an irreversible inhibitor of epidermal growth factor receptor (EGFR) sensitizing and T790M resistance mutations (IC50s = 15-17 nM) while sparing the wild-type form of the receptor (IC50 = 480 nM). It binds the related IGF1R and hERG receptors with significantly reduced potency (IC50s = 2.9 and 16.2 μM, respectively). AZD 9291 has been shown to inhibit tumor growth in a xenograft mouse model at oral doses of 5-10 mg/kg and has been tested clinically in patients with advanced EGFR mutant non-small-cell lung cancer.[Cayman Chemical]
Description
AZD-9291 (Mesylate), also known as Osimertinib, belongs to a third-generation EGFR (epidermal growth factor receptor) inhibitor. It can be used for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) in case when the cancer cells carry specific mutations (such as T790M) in the epidermal growth factor receptor. It takes effect through directly binding to the certain mutant forms of EGFR (T790M, L858R, and exon 19 deletions) that are frequently found in NSCLC, further causing poor prognosis for late-stage disease. Since it spares wild type EGFR during therapy, it has only limited toxicity.
Definition
ChEBI: A member of the class of aminopyrimidines that is 4-(1-methylindol-3-yl)pyrimidin-2-amine in which one of the amino hydrogens is replaced by a 2-methoxy-4-[2-(dimethylamino)ethyl](methyl)amino-5-acrylamidophenyl group. Used (as the mesylate salt) for treat
ent of EGFR T790M mutation positive non-small cell lung cancer.
Indications
The collection of ibrutinib (Imbruvica(R), Pharmacyclics Inc.), afatinib, and osimertinib represents the small, yet expanding, group of covalent SMKIs. Ibrutinib is a non-receptor Bruton’s tyrosine kinase inhibitor approved for the treatment of relapsed chronic lymphocytic leukemia. Afatinib, approved for NSCLC in 2013 and squamous NSCLC in 2016, is a second-generation irreversible EGFR inhibitor that targets wild-type EGFR, the mutant T790M EGFR, and HER2. Osimertinib (AZD9291), which was approved by FDA in November 2015, is a third-generation irreversible EGFR inhibitor that selectively targets the mutant T790M EGFR. Rociletinib, which shares a high degree of structural similarity with that of osimertinib, is a promising covalent EGFR inhibitor developed by Clovis Oncology aimed for the treatment of patients with EGFR T790M-mutated NSCLC, until the company terminated its development in May 2016 following a negative vote fromthe FDA’sOncologic Drugs Advisory Committee.
References
http://www.medkoo.com/products/6711
https://en.wikipedia.org/wiki/Osimertinib
https://www.drugbank.ca/drugs/DB09330
Check Digit Verification of cas no
The CAS Registry Mumber 1421373-65-0 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,4,2,1,3,7 and 3 respectively; the second part has 2 digits, 6 and 5 respectively.
Calculate Digit Verification of CAS Registry Number 1421373-65:
(9*1)+(8*4)+(7*2)+(6*1)+(5*3)+(4*7)+(3*3)+(2*6)+(1*5)=130
130 % 10 = 0
So 1421373-65-0 is a valid CAS Registry Number.
1421373-65-0Relevant articles and documents
Compound for inhibiting three-mutant epidermal growth factor receptor tyrosine kinase and application thereof
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, (2021/09/15)
The invention discloses a compound for inhibiting three-mutant epidermal growth factor receptor tyrosine kinase, and is characterized in that the structural formula is as follows. Among them: Substituent R1 . One of: Substituent R2 . One of: The substituent X is H or Cl. Substituent R3 To H. One of the following.
Improvements in the Synthesis of the Third-Generation EGFR Inhibitor Osimertinib
Alivertis, Dimitrios,Skobridis, Konstantinos,Voulgari, Pinelopi
, (2021/10/19)
Osimertinib, a third generation potent and specific EGFR inhibitor is an important drug against many forms of cancer. It was synthesized by an improved and highly efficient protocol, revisiting the classical synthetic process and modifying parameters, such as solvents, temperature, reagents, and reaction time. A cost-effective, environmentally friendly methodology for the synthesis of osimertinib was established, which gave shorter reaction times, saved labor by eliminating purification steps through column chromatography, and enhanced yields. Four of the seven steps in total, were proceeded quantitatively or almost quantitatively (ca. 98 %). This synthetic protocol provides a very high overall yield, up to 68 %. In addition, the entire approach enables the preparation of osimertinib analogues and could be extended in the synthesis of other structurally similar bioactive compounds.
Method for industrially synthesizing AZD9291
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Paragraph 0035-0042, (2021/02/13)
The invention relates to a preparation method of AZD9291. Thepreparation method of AZD9291 comprises the steps of taking N-2- [ [2- (dimethylamino) ethyl ] methylamino ] -4-methoxy-5- [ [4- (1-methyl-1H-indol-3-yl) -2-pyrimidinyl ] amino ] aniline and acrylic acid as raw materials, taking an alcohol reagent as a reaction solvent, taking a hierarchical pore ZSM-5 molecular sieve as a catalyst, andtaking petroleum ether as a water carrying agent to react to obtain the AZD9291.