Madan deodhar biography of michael jackson

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Shraddha Walker, a year-old Maharashtrian Indian woman, suffered a horrible end in when she was murdered in a horrifying manner. Her life narrative depicts both sadness and aspiration.

Early Life and Career Path

Vasai, Maharashtra, is the place of Shraddha Walker's birth. She was of the Koli caste and came from a Hindu family. She lost her mother, Suman Madan Walker when she was a young child and was raised by her father, Vikash Madan Walker, and her younger brother, Shreejay Walker.

In April , Shraddha Walker began her professional career by working as a customer service representative for a company in Mumbai. While she was employed as a sales Manager at a retail sports store in Dahisar, Maharashtra, from to , her career took a number of unexpected turns. She made the decision to concentrate on her studies and set out to pass the final examinations for her public media program despite the difficulties caused by the COVID outbreak. She then changed jobs, joining an IT company where she quickly rose through the ranks to become a team leader.

Education and Employment

Shraddha attended the VIVA Institute of Technology in Virar, Maharashtra, where she studied public media, but she left during her final year. She held a number of positions at a retail sports store, including those of Sales Manager and Customer Service Representative. Later, she worked for an IT company, where she eventually became a team leader.

Love and Loss

In , Shraddha met Aftab Poonawala on the dating app "Bumble," and her life took a sad turn. As their romance developed, they ultimately decided to relocate to Delhi in March , settling in the Chhatarpur neighborhood. There are many stories regarding why they moved; some say it was because of family opposition, while others say it was because of Aftab's job. But as Shraddha's friend disclosed that she had told them about Aftab's aggressive tendencies, alarming indications started to surface. She was st

Abstract

Janus kinase (JAK) is a family of cytoplasmic non-receptor tyrosine kinases that includes four members, namely JAK1, JAK2, JAK3, and TYK2. The JAKs transduce cytokine signaling through the JAK-STAT pathway, which regulates the transcription of several genes involved in inflammatory, immune, and cancer conditions. Targeting the JAK family kinases with small-molecule inhibitors has proved to be effective in the treatment of different types of diseases. In the current review, eleven of the JAK inhibitors that received approval for clinical use have been discussed. These drugs are abrocitinib, baricitinib, delgocitinib, fedratinib, filgotinib, oclacitinib, pacritinib, peficitinib, ruxolitinib, tofacitinib, and upadacitinib. The aim of the current review was to provide an integrated overview of the chemical and pharmacological data of the globally approved JAK inhibitors. The synthetic routes of the eleven drugs were described. In addition, their inhibitory activities against different kinases and their pharmacological uses have also been explained. Moreover, their crystal structures with different kinases were summarized, with a primary focus on their binding modes and interactions. The proposed metabolic pathways and metabolites of these drugs were also illustrated. To sum up, the data in the current review could help in the design of new JAK inhibitors with potential therapeutic benefits in inflammatory and autoimmune diseases.

Keywords: JAK, synthesis, kinase inhibitory activity, pharmacological uses, binding mode/interactions

1. Introduction

Janus kinases (JAKs) are intracellular, non-receptor tyrosine kinases [1]. The JAK family consists of four members, including JAK1, JAK2, JAK3, and TY2K. Since the first discovery of JAKs by Wilks thirty years ago [2], great efforts have been made to understand their structure and functions. The four JAKs play an essential role in the transduction of the cytokine-mediated signals, which takes place through the