Vascular adhesion protein‐1 (VAP‐1) plays a dual role with its adhesive and enzymatic properties, facilitating leukocyte migration to sites of inflammation and catalyzing the breakdown of primary amines into harmful by‐products, which are linked to diabetic complications. Present in various tissues, VAP‐1 also circulates in a soluble form in the bloodstream. Diabetes is associated with several complications such as cardiovascular disease, retinopathy, nephropathy, and neuropathy, significantly contributing to disability and mortality. These complications arise from hyperglycemia‐induced oxidative stress, inflammation, and the formation of advanced glycation end‐products (AGEs). Earlier research, including our own from the 1990s and early 2000s, has underscored the critical role of VAP‐1 in these pathological processes, prompting extensive investigation into its contribution to diabetic complications. In this review, we examine the involvement of VAP‐1 in diabetes and its complications, alongside its link to other conditions related to diabetes, such as cancer and metabolic dysfunction‐associated fatty liver disease. We also explore the utility of soluble VAP‐1 as a biomarker for diabetes, its complications, and other related conditions. Since the inhibition of VAP‐1 to treat diabetic complications is a novel and promising treatment option, further studies are needed to translate the beneficial effect of VAP‐1 inhibitors observed in animal studies to clinical trials recruiting human subjects. Besides, future studies should focus on using serum sVAP‐1 levels for risk assessment in diabetic patients, identifying those who need intensive glycemic control, and determining the patient population that would benefit most from VAP‐1 inhibitor therapies.

2024-06-13·JOURNAL OF MEDICINAL CHEMISTRY

Discovery of the Selective and Orally Available Galectin-1 Inhibitor GB1908 as a Potential Treatment for Lung Cancer

Article

作者: Leffler, Hakon ; Andréasson Dahlgren, Kajsa ; Zarrizi, Reihaneh ; Zetterberg, Fredrik R ; Peterson, Kristoffer ; Diehl, Carl ; Håkansson, Maria ; Slack, Robert J ; Khabut, Areej ; Pedersen, Anders ; Nilsson, Ulf J ; MacKinnon, Alison C ; Holyer, Ian ; Kahl-Knutson, Barbro ; Roper, James A

We have previously described a new series of selective and orally available galectin-1 inhibitors resulting in the thiazole-containing glycomimetic GB1490. Here, we show that the introduction of polar substituents to the thiazole ring results in galectin-1-specific compounds with low nM affinities. X-ray structural analysis of a new ligand-galectin-1 complex shows changes in the binding mode and ligand-protein hydrogen bond interactions compared to the GB1490-galectin-1 complex. These new high affinity ligands were further optimized with respect to affinity and ADME properties resulting in the galectin-1-selective GB1908 (K_d galectin-1/3 0.057/6.0 μM). In vitro GB1908 inhibited galectin-1-induced apoptosis in Jurkat cells (IC₅₀ = 850 nM). Pharmacokinetic experiments in mice revealed that a dose of 30 mg/kg b.i.d. results in free levels of GB1908 in plasma over galectin-1 K_d for 24 h. GB1908 dosed with this regimen reduced the growth of primary lung tumor LL/2 in a syngeneic mouse model.

2024-05-02·Future medicinal chemistry

Design and synthesis of novel coumarin–benzimidazole hybrids as human galectin-1 inhibitors

Article

作者: Nerella, Sridhar G ; Alvala, Ravi ; Kalle, Arunasree M ; Alvala, Mallika

Aim: To develop novel non-carbohydrate inhibitors of human galectin-1 (GAL-1), we have designed a series of coumarin-benzimidazole hybrids. Methods: We synthesized and characterized the coumarin-benzimidazole hybrids and further evaluated them using an in vitro GAL-1 enzyme-linked immunosorbent assay and in silico methods. Results: Among all, the compounds 6p and 6q were found to be potent, with GAL-1 inhibition of 37.61 and 36.92%, respectively, at 10 μM in GAL-1-expressed cell culture supernatant of MCF-7 cells. These two compounds are feasible for fluorine-18 radiolabeling to develop GAL-1 selective PET radiotracers. Computational studies revealed strong binding interactions of GAL-1 with these novel coumarin-benzimidazole hybrids. Conclusion: Coumarin-benzimidazole hybrids can serve as potential leads to develop selective non-carbohydrate GAL-1 inhibitors for cancer therapy.

项与 RTU-1096 相关的新闻（医药）

2023-10-26

·PipelineReview

CatalYm commences Dosing in a Phase 2 Study with Visugromab in Combination with Neoadjuvant Immunotherapy in Treatment-naive Muscle Invasive Bladder Cancer Patients

MUNICH, Germany I October 26, 2023 I CatalYm today announced that the first patient has been dosed in the Phase 2 clinical trial, GDFather-NEO ( NCT06059547 ), evaluating its lead anti-GDF-15 antibody candidate, visugromab, in combination with neoadjuvant immunotherapy (nivolumab, aPD-1 inhibitor) in muscle invasive bladder cancer (MIBC). The exploratory study expands visugromab’s clinical Phase 2 evaluation to a therapeutic front-line setting, building on the positive results from the ongoing GDFather-2 ( NCT04725474 ) trial in last-line metastatic patients with a range of advanced, treatment-resistant solid tumors. “Visugromab offers a very distinct mechanism of action that has the potential to break key immunotherapy resistance mechanisms preventing aPD-1 therapy to fully deliver,” commented Prof. Dr. Andrea Necchi, Director of Genitourinary Medical Oncology at IRCCS San Raffaele Hospital and Principal Investigator of the study. “Based on the encouraging efficacy signs achieved with the visugromab-nivolumab combination in the last-line setting, we are looking forward to exploring this new approach in the front-line setting to open new avenues for the treatment of early-stage bladder cancer.” “This study provides us with the first opportunity to evaluate visugromab in an earlier clinical setting and allows us to gain a deeper understanding of its immunosupportive activity. It will also offer us expanded reference data on response-predictive biomarkers and provide further insights into visugromab’s extensive therapeutic potential for patients with hard-to-treat cancers that have built immune-resistance mechanisms,” added Dr. Phil L’Huillier, Chief Executive Officer at CatalYm. The exploratory, controlled GDFATHER-NEO Phase 2 study is assessing the safety and initial signs of clinical efficacy of a combination treatment of nivolumab plus visugromab compared to nivolumab plus placebo in patients with MIBC who are set to undergo radical cystectomy and cannot or refuse to receive cisplatin-based chemotherapy. In addition, the study will provide data on potential response-predictive biomarkers for patient stratification. The trial will be led from Milan, Italy, and will enroll 30 patients in a 1:1 setting at four sites in Italy. About the GDFATHER-2 Trials The GDFATHER-2 trials ( GDF -15 A ntibody-media T ed H uman E ffector cell R elocation Phase 2 ) ( NCT04725474 ) are ongoing first-in-human Phase 2a cohorts investigating the effect of visugromab (CTL-002) as monotherapy and/or in combination with a PD-1 checkpoint inhibitor in patients with various advanced-stage, relapse/refractory solid tumors and the new biomarker-selected cohort. The study consists of two segments with a total of up to seven cohorts, enrolling up to 164 patients in Simon-2-stage designs to confirm a certain response rate within each tumor type. Five cohorts are within tumor types with anti-PD1/-L1 label, recruiting patients that either were refractory to or relapsed post prior anti-PD1/-L1 treatment. One cohort entails treatment of an anti-PD1/-L1 naïve tumor type in an indication without anti-PD1/-L1 approval and one tumor-agnostic cohort evaluates patient-selection based on two novel predictive biomarkers. In addition the company is also evaluating visugromab in an exploratory Phase 2 study GDFather-NEO ( NCT06059547 ) in combination with neoadjuvant immunotherapy in first-line muscle invasive bladder cancer. About Visugromab (CTL-002) Visugromab is a monoclonal antibody that neutralizes the tumor-derived Growth Differentiation Factor-15 (GDF-15), a locally acting immunosuppressant fostering immunotherapy resistance. Neutralizing GDF-15 with visugromab reverses key cancer resistance mechanisms to reinstate an efficient anti-tumor response by reenabling immune cell activation and tumor infiltration. Visugromab has already demonstrated a good safety profile and potent and durable anti-tumor efficacy in combination with anti-PD-1 treatment in advanced cancer patients. The antibody is currently being investigated in ongoing Phase 2 studies in multiple solid tumor indications. About CatalYm CatalYm has identified GDF-15 as a key cancer therapy resistance mechanism and is developing a safe and efficacious immune therapy for solid tumors. GDF-15, an immunosuppressant important for feto-maternal tolerance, is hijacked by cancer cells to evade immune system attack. Visugromab, CatalYm’s lead antibody, has demonstrated durable anti-tumor efficacy with long-lasting objective responses in relapsed and refractory metastatic solid tumor patients in combination with anti-PD-1. CatalYm is now advancing to Phase 2b studies to confirm visugromab as a new class of cancer immunotherapy in a broad range of anti-cancer regimens. SOURCE: CatalYm

临床2期免疫疗法临床结果

2023-02-02

·BioSpace

Terns Pharmaceuticals to Participate in Guggenheim Healthcare Talks 2023 Oncology Conference

FOSTER CITY, Calif., Feb. 02, 2023 (GLOBE NEWSWIRE) -- Terns Pharmaceuticals, Inc. (“Terns” or the “Company”) (Nasdaq: TERN), a clinical-stage biopharmaceutical company developing a portfolio of small-molecule product candidates to address serious diseases, including oncology, obesity and non-alcoholic steatohepatitis (NASH), today announced that management will participate in a fireside chat at the Guggenheim Healthcare Talks 2023 Oncology Conference on Thursday, February 9, 2023 at 10:10 a.m. ET. A live audio webcast of the event will be available on the investor relations page of the Terns Pharmaceuticals website at . A replay of the webcast will be archived on Terns’ website for 30 days following the event. About Terns Pharmaceuticals Terns Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company developing a portfolio of small-molecule product candidates to address serious diseases, including oncology, obesity and NASH. Terns’ pipeline includes four clinical stage development programs including an allosteric BCR-ABL inhibitor, a THR-β agonist, an FXR agonist, a VAP-1 inhibitor, and preclinical small-molecule GLP-1 receptor agonist and GIPR modulator programs. For more information, please visit: . Contacts for Terns Investors Justin Ng investors@ternspharma.com Media Jenna Urban Berry & Company Public Relations media@ternspharma.com

2022-12-23

·GlobeNewswire-Health Care

Terns Announces Closing of Public Offering of Shares of Common Stock, Including Full Exercise of Underwriters’ Option to Purchase Additional Shares

FOSTER CITY, Calif., Dec. 23, 2022 (GLOBE NEWSWIRE) -- Terns Pharmaceuticals, Inc. (“Terns” or the “Company”) (Nasdaq: TERN), a clinical-stage biopharmaceutical company developing a portfolio of small-molecule product candidates to address serious diseases, including oncology, obesity and non-alcoholic steatohepatitis (NASH), today announced the closing of its previously announced underwritten public offering of 11,902,500 shares of its common stock, including 1,552,500 shares sold pursuant to the underwriters’ exercise in full of their option to purchase additional shares, at a public offering price of $7.25 per share, before underwriting discounts and commissions. The gross proceeds from the offering, before deducting underwriting discounts and commissions and other offering expenses payable by Terns, are approximately $86.3 million. All of the securities were offered by Terns. Jefferies and Cowen acted as lead book-running managers for the offering. UBS Investment Bank also acted as a bookrunner for the offering. Mizuho and JMP Securities, a Citizens Company, acted as co-lead managers for the offering. Terns intends to use the net proceeds from the offering, together with its existing cash and cash equivalents, to advance its clinical-stage development pipeline, including the TERN-501, TERN-701 and TERN-601 clinical programs and for working capital and general corporate purposes. The public offering was made pursuant to a registration statement on Form S-3 previously filed with the Securities and Exchange Commission (“SEC”), which became effective on March 14, 2022. A prospectus supplement and accompanying prospectus relating to the offering was filed with the SEC and is available on the SEC’s website located at www.sec.gov. Copies of the prospectus supplement and accompanying prospectus relating to this offering may be obtained from Jefferies LLC, Attention: Equity Syndicate Prospectus Department, 520 Madison Avenue, New York, NY 10022, by telephone at 877-821-7388 or by email at prospectus_department@jefferies.com or Cowen and Company, LLC, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, New York 11717, by telephone at 1-833-297-2926 or by e-mail: PostSaleManualRequests@broadridge.com. This press release shall not constitute an offer to sell or a solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification of these securities under the securities laws of any such state or other jurisdiction. About Terns Pharmaceuticals Terns Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company developing a portfolio of small-molecule product candidates to address serious diseases, including oncology, obesity and NASH. Terns’ pipeline includes four clinical stage development programs including an allosteric BCR-ABL inhibitor, a THR-β agonist, an FXR agonist, a VAP-1 inhibitor, and a preclinical small-molecule GLP-1 receptor agonist program. Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements about Terns Pharmaceuticals, Inc. (the “Company,” “we,” “us,” or “our”) within the meaning of the federal securities laws, including those related to the use of proceeds of the offering. All statements other than statements of historical facts contained in this press release are forward-looking statements. In some cases, you can identify forward-looking statements by terminology such as “aim,” “anticipate,” “assume,” “believe,” “contemplate,” “continue,” “could,” “design,” “due,” “estimate,” “expect,” “goal,” “intend,” “may,” “objective,” “plan,” “positioned,” “potential,” “predict,” “seek,” “should,” “target,” “will,” “would” and other similar expressions that are predictions of or indicate future events and future trends, or the negative of these terms or other comparable terminology. The Company has based these forward-looking statements largely on its current expectations, estimates, forecasts and projections about future events and financial trends that it believes may affect its financial condition, results of operations, business strategy and financial needs. In light of the significant uncertainties in these forward-looking statements, you should not rely upon forward-looking statements as predictions of future events. These statements are subject to risks and uncertainties that could cause the actual results and the implementation of the Company’s plans to vary materially, including the risks associated with the initiation, cost, timing, progress, results and utility of the Company’s current and future research and development activities and preclinical studies and clinical trials. These risks are not exhaustive. For a detailed discussion of the risk factors that could affect the Company and the offering, please refer to the risk factors identified in the Company’s SEC reports, including but not limited to its Annual Report on Form 10-K for the year ended December 31, 2021 and its Quarterly Report on Form 10-Q for the period ended September 30, 2022, and its prospectus supplement. Except as required by law, the Company undertakes no obligation to update publicly any forward-looking statements for any reason. Contacts for Terns Investors Justin Nginvestors@ternspharma.com MediaJenna UrbanBerry & Company Public Relationsmedia@ternspharma.com

100 项与 RTU-1096 相关的药物交易

登录后查看更多信息

研发状态

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
特应性皮炎	临床1期	-	Sucampo Pharmaceuticals LLC	-
糖尿病性黄斑水肿	临床1期	-	Sucampo Pharmaceuticals LLC	-
银屑病	临床1期	-	Sucampo Pharmaceuticals LLC	-