Latest news with #ALK5
The Hindu
29-07-2025
- Health
- The Hindu
SB43154 drug used in cancer research shows promise against COVID-19 in preclinical studies: Scientists
After a long battle and research, Indian scientists have found out that a drug used in cancer studies has the potential to provide substantial protection against the coronavirus infection in preclinical studies. Remarkably, even after more than 50 consecutive generations exposed to the drug, the virus was unable to develop resistance. Scientists from the Indian Council of Medical Research (ICMR) and Indian Council of Agricultural Research (ICAR) have jointly found that the drug -- SB431542, an ALK5 inhibitor -- is highly effective against the coronavirus. Study findings This discovery was a collaborative effort between the National Centre for Veterinary Type Culture in Hisar and National Institute of Virology (NIV) under the ICMR in Pune, said NIV Director Dr Naveen Kumar. The study was first released as a preprint on bioRxiv and has since been accepted for publication in the Journal of Virology. If future human trials confirm its effectiveness, the drug could become a groundbreaking tool in the fight against COVID-19. Since December 2019, when the coronavirus emerged from China's Wuhan, it has spread to nearly every country in the world. Since 2020, more than 30 anti-Covid vaccines have received the World Health Organization's (WHO) approval for global use. "However, health experts believe vaccines alone are not enough. The virus continues to mutate, and many existing treatments like Remdesivir and monoclonal antibodies will quickly lose effectiveness," Kumar said. In this context, Indian scientists have been screening small molecule inhibitors that mainly target cellular kinases and phosphatases. One such compound, SB431542 -- originally developed to block TGF-β (Transforming Growth Factor-beta) signalling and commonly used in preclinical cancer, inflammation and fibrosis research -- has now been found by Indian researchers to also inhibit the coronavirus effectively. Kumar explained that SB431542 fights the virus in three fronts. It first blocks the virus from entering human cells by targeting the TGF-β/Smad pathway. Secondly, it disrupts the ability of the virus to assemble inside cells by interfering with ORF3a-related lysosomal dysfunction. Finally, it prevents the virus from killing the infected cell (a process called apoptosis), which helps stop the virus from escaping and spreading to other cells. This three-pronged approach has not been observed in any existing antiviral drug. Interestingly, the drug acted through both direct and indirect mechanisms -- it directly targets the viral ORF3a protein and indirectly hinders the virus by blocking the host cell's TGF-β signaling pathway. SB431542 was also tested against the chicken coronavirus (Infectious Bronchitis Virus or IBV) in specific pathogen-free chicken embryos. Embryos treated with the drug developed normally and showed no mortality, while those in the untreated control group failed to develop properly and did not survive. Kumar emphasised that even after exposing the virus to the drug over 50 successive generations (passage), it failed to develop resistance. This suggests that the chances of the virus evolving a drug-resistant variant against this compound are extremely low. This is a major advancement over existing antivirals like Remdesivir, against which the virus builds resistance quickly.
The Print
28-07-2025
- Health
- The Print
SB43154 drug used in cancer research shows promise against COVID-19 in preclinical studies: Scientists
This discovery was a collaborative effort between the National Centre for Veterinary Type Culture in Hisar and National Institute of Virology (NIV) under the ICMR in Pune, said NIV Director Dr Naveen Kumar. Remarkably, even after more than 50 consecutive generations exposed to the drug, the virus was unable to develop resistance. Scientists from the Indian Council of Medical Research (ICMR) and Indian Council of Agricultural Research (ICAR) have jointly found that the drug — SB431542, an ALK5 inhibitor — is highly effective against the coronavirus. New Delhi, Jul 28 (PTI) After a long battle and research, Indian scientists have found out that a drug used in cancer studies has the potential to provide substantial protection against the coronavirus infection in preclinical studies. The study was first released as a preprint on bioRxiv and has since been accepted for publication in the Journal of Virology. If future human trials confirm its effectiveness, the drug could become a groundbreaking tool in the fight against COVID-19. Since December 2019, when the coronavirus emerged from China's Wuhan, it has spread to nearly every country in the world. Since 2020, more than 30 anti-Covid vaccines have received the World Health Organization's (WHO) approval for global use. 'However, health experts believe vaccines alone are not enough. The virus continues to mutate, and many existing treatments like Remdesivir and monoclonal antibodies will quickly lose effectiveness,' Kumar said. In this context, Indian scientists have been screening small molecule inhibitors that mainly target cellular kinases and phosphatases. One such compound, SB431542 — originally developed to block TGF-β (Transforming Growth Factor-beta) signalling and commonly used in preclinical cancer, inflammation and fibrosis research — has now been found by Indian researchers to also inhibit the coronavirus effectively. Kumar explained that SB431542 fights the virus in three fronts. It first blocks the virus from entering human cells by targeting the TGF-β/Smad pathway. Secondly, it disrupts the ability of the virus to assemble inside cells by interfering with ORF3a-related lysosomal dysfunction. Finally, it prevents the virus from killing the infected cell (a process called apoptosis), which helps stop the virus from escaping and spreading to other cells. This three-pronged approach has not been observed in any existing antiviral drug. Interestingly, the drug acted through both direct and indirect mechanisms — it directly targets the viral ORF3a protein and indirectly hinders the virus by blocking the host cell's TGF-β signaling pathway. SB431542 was also tested against the chicken coronavirus (Infectious Bronchitis Virus or IBV) in specific pathogen-free chicken embryos. Embryos treated with the drug developed normally and showed no mortality, while those in the untreated control group failed to develop properly and did not survive. Kumar emphasised that even after exposing the virus to the drug over 50 successive generations (passage), it failed to develop resistance. This suggests that the chances of the virus evolving a drug-resistant variant against this compound are extremely low. This is a major advancement over existing antivirals like Remdesivir, against which the virus builds resistance quickly. PTI PLB RC This report is auto-generated from PTI news service. ThePrint holds no responsibility for its content.
Associated Press
10-03-2025
- Health
- Associated Press
Agomab Announces Positive Topline Phase 2a Interim Results for AGMB-129 in Fibrostenosing Crohn's Disease
Agomab Therapeutics NV ('Agomab') today announced positive interim results from 44 patients completing treatment in the ongoing STENOVA 1 Phase 2a clinical trial for AGMB-129, an oral gastro-intestinal (GI)-restricted small molecule inhibitor of ALK5 (TGF-β RI or ALK5) for the potential treatment of Fibrostenosing Crohn's Disease (FSCD). STENOVA is a randomized, double-blind, placebo-controlled study in a total of 90 patients with symptomatic FSCD. Patients are randomized to receive one of two doses of AGMB-129 or placebo for 12 weeks on top of standard of care, including biologics. The multi-center study is global with investigational sites in the USA, Canada and Europe. The primary endpoints are the safety and tolerability of AGMB-129 in FSCD patients. Secondary endpoints include the pharmacokinetics and target engagement at the site of the ileal strictures as measured through transcriptomics. All primary and secondary endpoints were met. The company has also initiated the open-label treatment extension of the STENOVA study with AGMB-129. Study participants who have completed the double-blind 12-week treatment period are eligible to participate and can receive treatment for up to an additional 48 weeks. 'The positive interim data for the STENOVA Phase 2a clinical trial represent a significant milestone for this program, and we look forward to presenting the detailed results at a scientific conference in the near-term,' said Philippe Wiesel, Chief Medical Officer at Agomab Therapeutics. 'We want to thank all patients and investigators for participating in this trailblazing study, which aims to address the high unmet medical need that exists in the field of Fibrostenosing Crohn's disease.' AGMB-129 is an investigational drug and not approved by any regulatory authority. Its efficacy and safety have not been established. About AGMB-129 AGMB-129 is an oral, small molecule GI-restricted inhibitor of ALK5 (or TGF-β RI) currently in clinical development for the treatment of Fibrostenosing Crohn's Disease (FSCD). TGF-β is a major driver of fibrosis. AGMB-129 is specifically designed to inhibit ALK5/TGF-β in the GI-tract. Rapid first-pass metabolism in the liver prevents clinically relevant systemic exposure, potentially delivering an improved safety profile over systemically available inhibitors in this class. In a Phase 1 trial in healthy subjects, single- and multiple-dose AGMB-129 was generally well-tolerated at all doses tested. In addition, the trial showed high local exposure to AGMB-129 in the ileum but no clinically relevant systemic exposure, demonstrating that the GI restricted mechanism may operate efficiently in humans. Fibrostenosing complications occur in nearly 50% of Crohn's disease patients and are the leading cause of bowel resection surgery, however there are no approved specific therapies for FSCD. AGMB-129 has received U.S. FDA Fast Track Designation. About Agomab Agomab is focused on achieving disease modification by modulating inflammation and fibrosis in chronic indications such as Fibrostenosing Crohn's Disease and Idiopathic Pulmonary Fibrosis. We do this by targeting biologically validated pathways, including Transforming Growth Factor β, and by applying specialized capabilities in organ-restricted small molecules. With a differentiated clinical pipeline across several fibrotic disorders, end-to-end research and development capabilities, a proven track-record and a strong investor base, Agomab is building a transformational company with the aim to have a real impact on patients. Sofie Van Gijsel VP of Investor Relations Phone: +1 781 296 1143Media Requests for Agomab Dr. Stephanie May Trophic Communications Phone: +49 171 1855682 KEYWORD: BELGIUM EUROPE SOURCE: Agomab Therapeutics NV Copyright Business Wire 2025. PUB: 03/10/2025 06:00 AM/DISC: 03/10/2025 06:00 AM
