1234293-70-9

Basic information

• Product Name: 1-[2-chloro-2-(4-fluorophenyl)ethyl]-N-(3-fluorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine
• Synonyms: 1-[2-chloro-2-(4-fluorophenyl)ethyl]-N-(3-fluorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine
• CAS NO: 1234293-70-9
• Molecular Weight: 385.803
• Mol File: 1234293-70-9.mol

Chemical Properties

• CAS DataBase Reference: 1-[2-chloro-2-(4-fluorophenyl)ethyl]-N-(3-fluorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine(CAS DataBase Reference)
• NIST Chemistry Reference: 1-[2-chloro-2-(4-fluorophenyl)ethyl]-N-(3-fluorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine(1234293-70-9)
• EPA Substance Registry System: 1-[2-chloro-2-(4-fluorophenyl)ethyl]-N-(3-fluorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine(1234293-70-9)

Safety Data

• Hazardous Substances Data: 1234293-70-9(Hazardous Substances Data)

Upstream product

• 372-19-0 meta-fluoroaniline 
• 1013930-73-8 4-chloro-1-[2-chloro-2-(4-fluorophenyl)ethyl]-1H-pyrazolo[3,4-d]-pyrimidine 

Relevant articles and documents

Dual Src and Abl inhibitors target wild type Abl and the AblT315I Imatinib-resistant mutant with different mechanisms

The tyrosine kinase Src and its close homolog Abl, both play important roles in chronic myelogenous leukemia (CML) progression and Imatinib resistance. No clinically approved inhibitors of the drug-resistant AblT315I exist to date. Here, we present a thorough kinetic analysis of two potent dual Src-Abl inhibitors towards wild type Src and Abl, and the AblT315I mutant. Our results show that the most potent compound BO1 shows only a modest loss of potency (fourfold) towards the AblT315I mutant in vitro and was an ATP-competitive inhibitor of wild type Abl but it acted as a non-competitive inhibitor in the case of AblT315I.

A cascade screening approach for the identification of Bcr-Abl myristate pocket binders active against wild type and T315I mutant

The major clinical challenge in drug-resistant chronic myelogenous leukemia (CML) is currently represented by the Bcr-Abl T315I mutant, which is unresponsive to treatment with common first and second generation ATP-competitive tyrosine kinase inhibitors (TKIs). Allosteric inhibition of Bcr-Abl represent a new frontier in the fight against resistant leukemia and few candidates have been identified in the last few years. Among these, myristate pocket (MP) binders discovered by Novartis (e.g. GNF2/5) showed promising results, although they proved to be active against the T315I mutant only in combination with first and second generation ATP-competitive inhibitors. Here we used a cascade screening approach based on sequential fluorescence polarization (FP) screening, in silico docking/dynamics studies and kinetic-enzymatic studies to identify novel MP binders. A pyrazolo[3,4-d]pyrimidine derivative (6) has been identified as a promising allosteric inhibitor active on 32D leukemia cell lines (expressing Bcr-Abl WT and T315I) with no need of combination with any ATP-competitive inhibitor.