Deaths from cancer or infections can occur when available treatments are ineffective. Once turned on, the pregnane X receptor (PXR) activates the expression of genes encoding enzymes that metabolize external chemicals, including drugs. This causes a significant drop in the effectiveness of chemotherapy, antivirals, and other pharmaceuticals. Blocking the PXR activity is notoriously difficult, as many drugs that bind the protein, whether intentionally or unintentionally, activate it. Scientists at St. Jude Children’s Research Hospital have leveraged chemical and structural studies in the design of PXR inhibitors to better understand this process. The findings, published in Nature Communications, provide new insights into the relationship between compounds that activate PXR and ones that block its activity, with implications for designing more effective therapeutics. Removing toxic compounds from our bodies is a vital process to maintain overall health and well-being. To accomplish this, the human body has a toxin-removal system. A family of proteins called cytochrome P450 plays a significant role in this process; however, these proteins do not discriminate between toxins and well-intentioned therapeutics. Higher drug doses are often needed to overcome the work these proteins do to eliminate drugs and toxins alike from the body. Cytochrome P450 protein levels are elevated when a drug binds to and activates their respective regulators, such as nuclear receptors, which in turn activates cytochrome P450 genes’ expression. In particular, PXR regulates the expression of a central player in drug metabolism, CYP3A4. “PXR is a transcription factor that regulates the gene expression of CYP3A4, and when a drug binds to and activates PXR, it upregulates CYP3A4,” said corresponding author Taosheng Chen, PhD, St. Jude Department of Chemical Biology & Therapeutics. “CYP3A4 metabolizes more than half of drugs on the market, so it’s clear how important it is.” CYP3A4 inhibitors, such as ritonavir, have shown benefit when used in combination with the anti-SARS-CoV-2 drug Paxlovid by stopping its active ingredient, nirmatrelvir, from being metabolized by CYP3A4 too quickly. Directly inhibiting PXR activity represents an alternative solution to control drug metabolism by CYP3A4. If drug-metabolizing proteins like CYP3A4 are the hired goons, then PXR represents the mob boss. The researchers’ challenge was overcoming generations of PXR evolution, which has turned the protein into a juggernaut of ligand promiscuity. “Lots of compounds can bind to PXR,” explained Chen. “There are even very small compounds that by themselves, are inactive. But if you combine a few of them, they can bind to different areas of PXR and together activate it.” The flexibility that allows it to bind thousands of different compounds also means inhibiting its function requires a deft touch. Previous work from the Chen lab on PXR inhibitor discovery identified the inhibitor SPA70 as a potent candidate. But as a testament to PXR’s unique capabilities, very minor changes to SPA70 flipped it into an activator rather than an inhibitor. In this study, Chen and his team leveraged chemical and structural studies to understand the molecular basis behind the subtle differences between activator and inhibitor binding. To address these differences, the researchers used X-ray crystallography to obtain the first-ever atomic structures of PXR bound to an inhibitor, presenting four new PXR structures with different inhibitors bound. These could be used to compare old and new structures of PXR bound to activators with almost identical chemical structures to the inhibitors to pinpoint the exact protein regions that govern PXR activity. “The activator and inhibitor structures are very similar, except that the activators interact with a region of PXR we call activation function-2, AF2,” said Chen. “The inhibitor failed to interact effectively.” The AF2 region appeared to be crucial in determining whether a drug would function as an activator or inhibitor. “When you have an activator, the conformation of the AF2 is different from that induced by an inhibitor. And it would favor either co-activator or co-repressor recruitment, respectively,” explained Chen. “So, it’s almost like a gatekeeper.” Building on the information gained from these structures, the researchers found they could flip the drugs between activator and inhibitor by rationally adding or taking away pieces of the molecules based on the identified “hot spots” within the protein. Chen hopes these findings will spark new research into more effective PXR inhibitors, which could potentially be used to prevent PXR-mediated drug metabolism. Garcia-Maldonado E, Huber AD, Chai SC et al.Chemical manipulation of an activation/inhibition switch in the nuclear receptor PXR.

The Pharmaceuticals Export Promotion Council of India (Pharmexcil), in collaboration with the Embassy of India in Armenia, is aiming to fortify trade relations and tap into the burgeoning pharmaceutical market in Armenia. In order to initiate the collaboration, Pharmexcil is all set to host a webinar titled “Armenia-India Collaborative Opportunities in the Pharmaceutical Sector” on May 17, 2024. Armenia, a promising market within the Commonwealth of Independent States (CIS) region, imported pharmaceuticals worth USD 213.7 million in 2022. The market is projected to grow to USD 548.4 million by 2027, reflecting a compound annual growth rate (CAGR) of 10.4%. Scheduled to commence at 17:30 IST (16:00 Armenian Time), the webinar will offer in-depth insights into Armenia’s regulatory framework, enabling Indian pharmaceutical companies to better navigate and engage with the Armenian market. The webinar will feature experts from Armenia discussing regulatory aspects and recent healthcare reforms aimed at Universal Health Insurance. This will equip participants with critical knowledge to leverage opportunities in the expanding Armenian market. Uday Bhaskar, director general (DG) of Pharmexcil, emphasized the significance of this event, stating, “I urge member companies to take advantage of this opportunity to explore and expand their presence in the Armenian health sector. The insights gained from this webinar will be invaluable for enhancing our exports to Armenia.” A Q&A session will follow the presentations, allowing participants to interact directly with Armenian stakeholders, fostering potential business collaborations.

Even as the Association of the Pharmacy Teachers of India is persistent on the implementation of a common pharmacist registration process at the national level, the pharmacy professionals in Karnataka highlight on the requirement of One Nation -One Registration benefits. Prof R Raveendra, charter president, Indian Pharmaceutical Association, Peenya Branch, Bengaluru and professor, Department of Pharmaceutical Chemistry, Cauvery College of Pharmacy, Mysuru said the One Nation-One Ration card facility has helped every Indian to get their ration even after migration to other states due to employment and other reasons. In a similar way, the registered pharmacist has to get the right opportunity to work anywhere in India. Once they register their name as registered pharmacist in any State Pharmacy Council the recognition of this status should be automatic. The government and PCI already initiated the process of linking Aadhar card to registered pharmacist of any state pharmacy councils across India, this would give a further impetus to the whole process of One Nation-One Registration. Those who get the opportunity to work in different parts of India in pharmaceutical industry, research departments or community health services, Pharmacovigilance, or even in the academia, their expertise will only be an advantage to the sector, he added. In this regard, PCI should take immediate steps to frame a common guideline to all State Pharmacy Councils to ensure that all State Pharmacy Councils have to follow the same guidelines while registering as pharmacist. Another important aspect is the need to ensure life time registration to each and every registered pharmacist. Karnataka State Pharmacy Council has initiated a unique registration scheme along with social security insurance and health scheme. The One Nation-One Pharmacist registration can allow such initiatives too of pharmacist welfare, said Prof. Raveendra. Also each State Pharmacy Council should appoint senior teachers as pharmacy inspector as per Pharmacy Act to ensure that all pharmacy shops are functioning   under the presence of registered pharmacist only. If One Nation-One Pharmacist registration is approved then pharmacists can chip in their services anywhere and anytime as many a time there is a shortfall existing in pharmacy outlets for qualified hands, he said. Even the profession of a pharmacy faculty can be broadened if opportunities to  work in pharmacy outlets or an hospitals as counsellors to guide the patient regarding dosages and treatment.  The professional service of a pharmacist even as a faculty can stall self medication which is rampant in the country. Their broadened expertise can be utilised during their guidance to  student community . Aspects of drug to drug interactions and drug-food interactions are critical information that can be shared. This is where One Nation-One Pharmacist registration to bolster recognition of professionals, said Prof. Raveendra.

Discover the top pharmaceutical companies in India listed on the NSE, sorted from highest to lowest by market cap Pharmaceutical companies play a pivotal role in safeguarding public health and well-being. Their significance lies in their pursuit of groundbreaking research, innovation, and the development of life-saving medications. In this blog, we have compiled a list of the top pharma companies in India as listed on the NSE (National Stock Exchange of India). Top 10 pharma companies in India by market cap Below, we have sorted India’s top 10 pharma companies listed on the NSE according to their market caps, from highest to lowest. Note: All market cap data below is sourced from NSE India as of April 24, 2024. Rank Company Name Market Cap (Rs. Cr) Headquarter #1 Sun Pharma 3,65,178.78 Mumbai, Maharashtra #2 Cipla 1,13,915.46 Mumbai, Maharashtra #3 Divi’s Labs 1,05,921.96 Hyderabad, Telangana #4 Dr Reddy’s Labs 1,04,611.73 Hyderabad, Telangana #5 Zydus Life 96,497.84 Ahmedabad, Gujarat #6 Mankind Pharma 95,139.75 Delhi #7 Torrent Pharma 91,312.58 Ahmedabad, Gujarat #8 Lupin 74,617.69 Mumbai, Maharashtra #9 Aurobindo Pharma 67,441.53 Hyderabad, Telangana #10 Alkem Lab 58,431.42 Mumbai, Maharashtra Sun Pharma Managing Director: Dilip Shanghvi Net Sales (Cr.): 20,812.14 Sun Pharmaceutical Industries Limited is the largest pharmaceutical company in India and the sixth-largest generic pharmaceutical manufacturer in the world. It produces and sells pharmaceutical formulations and active pharmaceutical ingredients to over 100 countries worldwide. Recently, Sun Pharmaceutical acquired 100 percent of Libra Merger Ltd, an Israeli company. Cipla Managing Director: Dilip Shanghvi Net Sales (Cr.): 20,812.14 Sun Pharmaceutical Industries Limited is the largest pharmaceutical company in India and the sixth-largest generic pharmaceutical manufacturer in the world. It produces and sells pharmaceutical formulations and active pharmaceutical ingredients to over 100 countries worldwide. Recently, Sun Pharmaceutical acquired 100 percent of Libra Merger Ltd, an Israeli company. Divi’s Labs CEO: Dr. Kiran Divi Net Sales (Cr.): 7,625.30 Divi’s Laboratories Limited specializes in producing active pharmaceutical ingredients and intermediates. The company is engaged in the manufacturing and custom synthesis of generic APIs and intermediates. Zydus Life Managing Director: Sharvil P. Patel Net Sales (Cr.): 8,731.60 Founded in 1952 by Ramanbhai B. Patel and A Modi, Zydus Lifesciences Limited was known as Cadila Healthcare Limited. Today, Zydus Life is predominantly involved in the production of generic drugs. Mankind Pharma CEO: Sheetal Arora Net Sales (Cr.): 8,127.15 Incorporated in 1995, Mankind Pharma specialises in various therapeutic areas, offering products from antibiotics to gastrointestinal, cardiovascular, dermal, and erectile dysfunction medications. At the end of 2023, Mankind made an additional investment of £1 million in Actimed Therapeutics, showing a dedication to advancing treatments for cancer cachexia, amyotrophic lateral sclerosis, and multiple muscle wasting issues.  Torrent Pharma Chairman: Samir Mehta Net Sales (Cr.): 7,695.20 The Torrent Group owns Torrent Pharmaceuticals Ltd. Initially promoted by UN Mehta as Trinity Laboratories Ltd., it was later renamed Torrent Pharmaceuticals Ltd. Through strategic acquisitions and diversifications, Torrent Pharma has joined the ranks of the top pharmaceutical companies in India. Lupin CEO: Vinita D Gupta Net Sales (Cr.): 11,258.83 Lupin Limited is globally recognized as one of the largest generic pharmaceutical companies and India’s fifth-largest pharmaceutical company by revenue. Lupin’s key focus areas encompass pediatrics, cardiovascular, anti-infectives, diabetology, asthma, and anti-tuberculosis medications. Aurobindo Pharma CEO: Dr Sanjay Chaturvedi Net Sales (Cr.): 12,792.28 Aurobindo Pharma Limited specializes in producing generic pharmaceuticals and active pharmaceutical ingredients. Founded by Penaka Venkata Ramprasad Reddy and Kambam Nithyananda Reddy in 1986, the company has established itself as one of India’s top pharmaceutical companies. Notably, a subsidiary of the company recently received the USFDA’s (United States Food and Drug Administration) approval for the Posaconazole Injection to prevent severe fungal infections.  Alkem Lab CEO: Dr. Vikas Gupta Net Sales (Cr.): 9,054.55 Alkem Laboratories Limited focuses on manufacturing and selling pharmaceutical generics, formulations, and nutraceuticals. It has a global presence in addition to its strong presence in the Indian market. FAQs Which are the top 5 pharmaceutical companies in the world by market cap? Going by market cap, here are the top 5 pharmaceutical companies in the world as of April 29, 2024: Eli Lilly: Market cap $697.39 billion Novo Nordisk: Market cap $568.92 billion Johnson & Johnson: Market cap $352.16 billion Merck: Market cap $332.33 billion AbbVie: Market cap $282.63 billion   What is the growth rate of the pharmaceutical industry in India? The Indian Pharmaceutical industry is ranked third in pharmaceutical production by volume, having grown at a CAGR of 9.43 percent over the past nine years. According to IBEF, the industry is expected to grow to $65 billion by 2024 and $130 billion by 2030.