WNT3A

TOKYO, Aug. 23, 2023 /PRNewswire/ -- PeptiGrowth Inc (PeptiGrowth), a Japanese biotechnology company focusing on the development of synthetic peptide based growth factors and Orizuru Therapeutics, Inc(OZTx), a Japanese biopharmaceutical company focusing on the research and development of iPSC-derived regenerative medicine have entered into a joint development agreement to create a novel synthetic peptide that will replace a recombinant growth factor used in the manufacturing of regenerative medicine product developed by OZTx. Continue Reading OZTx, with the aim of social implementation of cell therapy products and innovative iPS cell-related technologies (platform innovation), is conducting research and development of regenerative medicine using iPS cell-derived cardiomyocytes and islet cells and supports commercialization of development candidate seeds through collaboration with commercial partnerships and academic institutions. PeptiGrowth is developing "synthetic peptide growth factors" that have the same functions as commercially available growth factors and cytokines by utilizing their proprietary peptide discovery technology: Peptide Discovery Platform System (PDPS). PeptiGrowth aims to contribute to expansion of the regenerative medicine and cell therapy industry by developing "synthetic peptide growth factors", thereby solving the problems of standards for biologically derived raw materials, quality uniformity, material stability, and high cost, currently faced by the industry. Under this agreement, PeptiGrowth will develop and supply multiple candidate peptides created by PDPS to OZTx. OZTx will use the provided candidate peptides as part of their in-house evaluation assay system to specify a few candidates that are promising as the growth factor alternative peptide. These candidate peptides will be optimized in terms of bioactivity, chemical stability, solubility, etc., to create novel chemically synthesized peptides that have the equivalent functions as conventional recombinant growth factors in cell proliferation and differentiation induction. The use of the synthetic peptide created under this agreement is expected to eliminate concerns about quality variations between production lots and reduce manufacturing cost, which have been a problem inherent in conventional recombinant growth factors, thereby enabling improved productivity and economic efficiency at OZTx. Kenji Nonaka, President at Orizuru Therapeutics, Inc. "We are very pleased with this collaboration with PeptiGrowth, which aims to promote the spread of regenerative medicine through innovative technologies and ideas. We recognize that quality variation and high manufacturing costs are two of the challenges that must be overcome in the development of regenerative medicine products, but we expect that this collaboration will enable us to make significant progress toward practical application and that the results will also benefit the regenerative medicine industry at large." Jiro Sugimoto, President at PeptiGrowth Inc. "It is a great honor for us to develop the novel growth factor alternative peptide in collaboration with Orizuru Therapeutics, a company that has attracted the attention of the regenerative medicine industry in the field of iPS cells. We hope that this collaboration of technologies originated from Japan will create innovative peptide that will be widely used in the global market and make a significant contribution to the industry." About PeptiGrowth Inc. Name ：PeptiGrowth Inc. Founded ：April 1st, 2020 Address ：6-1, Marunouchi 2-Chome, Chiyoda-ku, Tokyo, 100-8086, Japan President ：Jiro Sugimoto Business ：Conventional growth factors and cytokines used in the manufacturing of regenerative medicine and cell therapy products are facing various challenges such as lot-to-lot quality variation, potential contamination with biological impurities, low stability, and high cost. PeptiGrowth was established as a joint venture between Mitsubishi Corporation and PeptiDream Inc. with the missions to address and solve those challenges that regenerative medicine and cell therapy industry is facing. PeptiGrowth has been working on the development of a series of synthetic peptides that have the same functions as conventional growth factors and cytokines. Its peptides are completely chemically synthesized and animal component-free. We have already launched six products, and plan to launch growth factor substitute peptides with the same functions as VEGF, Wnt3a, PDGF-AA, bFGF, and TPO in 2023 and early of 2024. For more information, please visit About Orizuru Therapeutics, Inc. Name ：Orizuru Therapeutics, Inc. Founded ：April 9th, 2021 Address ：2-26-1 Muraoka-higashi, Fujisawa-shi, Kanagawa, 251-8555 Japan President ：Kenji Nonaka Business ：OZTx, founded in April 2021 by KYOTO-iCAP, is steadfast in its dedication to bringing hope for better health through the infinite power of science. To deliver cell therapies to patients, the company promotes the wide use of cell therapy products and innovative iPSC-related technology through the following activities: 1.Development of regenerative medical products through cell transplantation 2.Support for drug discovery research and development of regenerative medicine research platform using iPSC-related technology For more information, please visit Contacts for inquiries or additional information: PeptiGrowth Inc. E-mail: [email protected] TEL：+81-70-4503-1497 SOURCE PeptiGrowth Inc.

Researchers have captured images of an enzyme for Wnt lipidation, which is pivotal to human development and cancer and crucial for Wnt signaling activation. The findings shed light on the mechanisms behind this activity and could eventually lead to new drugs to treat various malignancies. Using UT Southwestern's Cryo-Electron Microscopy Facility, researchers have captured images of an enzyme for Wnt lipidation, which is pivotal to human development and cancer and crucial for Wnt signaling activation. The findings, reported in Nature, shed light on the mechanisms behind this activity and could eventually lead to new drugs to treat various malignancies. "We are able to push the research envelope further into the key area of cancer-related signaling pathways thanks to UT Southwestern's state-of-the-art cryo-electron microscopy (cryo-EM) facility," said Xiaochun Li, Ph.D., Associate Professor of Molecular Genetics and Biophysics, who co-led the study with Yang Liu, a fourth-year graduate student, and Xiaofeng Qi, Ph.D., a postdoctoral researcher. Both Mr. Liu and Dr. Qi work in the Li lab. "The revealed scientific mechanism could accelerate the development of novel cancer-fighting drugs toward advanced solid tumors." Scientists have long known that members of the Wnt family of proteins are pivotal for embryonic development, kicking off signaling pathways necessary for functions such as axis formation, cell fate specification, and cell proliferation and migration. When Wnt proteins were first discovered in the early 1980s, they were immediately associated with cancer; aberrant Wnt signaling is known to contribute to pancreatic cancer, melanoma, triple-negative breast cancer, and other types of malignancies. To perform their signaling functions, Dr. Li explained, Wnt proteins must first be activated by the addition of a lipid molecule, a job performed by an enzyme called Porcupine (PORCN). How this occurs structurally and the mechanism by which investigational drugs inhibit this activity have been unknown. To investigate, Dr. Li and his colleagues gathered cryo-EM images of four structures: PORCN bound to a co-enzyme called palmitoleoyl-CoA, which contributes the lipid molecule to activate Wnt; PORCN bound to LGK974, an investigational drug known to inhibit Wnt signaling; PORCN bound to LGK974 and WNT3A, a Wnt family member; and PORCN bound to an activated, lipid-modified WNT3A protein. Cryo-EM, a technique recognized by a 2017 Nobel Prize, freezes proteins in place to get atomic-resolution microscopic images. These images showed that WNT3A, PORCN, and palmitoleoyl-CoA come together in a sandwich-type configuration, with PORCN in the middle flanked by the two other precursors. When WNT3A and PORCN were incubated with LGK974 instead of palmitoleoyl-CoA, the investigational drug took the place of the palmitoleoyl-CoA, blocking its ability to bind and contribute the lipid molecule; without this lipid modification, Dr. Li said, WNT3A can't set off a signaling cascade. Additionally, the images solved a decades-old mystery as to why the lipid chain that modifies Wnt proteins differs structurally from that on a related protein called Hedgehog, which is also involved in human development and cancer and activated by lipid modification. While the lipid chain on Hedgehog is made of a saturated fatty acid, causing it to extend into a straight line, the one on PORCN is unsaturated, causing it to kink into a C-shape. The researchers found that this kink is necessary for the lipid chain to fit into a cavity on PORCN, a critical step before transferring it onto Wnt. Dr. Li noted that LGK974 is one of several drugs that affect Wnt signaling that is currently in clinical trials against various cancers. Knowing the atomic structures of Wnt, PORCN, palmitoleoyl-CoA, and their complexes could lead to drugs better designed to block these interactions. Dr. Li is a Rita C. and William P. Clements, Jr. Scholar in Biomedical Research. Other researchers who contributed to this study include Linda Donnelly, Tao Long, Rich W. Zhou, Yingyuan Sun, and Boyuan Wang of UTSW; and Nadia Elghobashi-Meinhardt of Technical University Berlin in Germany. This work was supported by grants from the Damon Runyon Cancer Foundation (DRR-53S-19), the National Institutes of Health (P01 HL020948, P01 HL160487, R01 GM135343), The Welch Foundation (I-1957), and the Life Sciences Research Foundation. Cryo-EM data were collected at the UT Southwestern Medical Center Cryo-EM Facility, funded in part by an award from the Cancer Prevention and Research Institute of Texas (RP170644).