作者: He, Chen ; Chen, Long ; Zhang, Baixue ; Duan, Yiping ; Zhong, Wenyi ; Xu, Jinyi ; Yao, Hong ; Xu, Shengtao ; Zhou, Pijun ; Chen, Jichao ; Wang, Tianyi

Hematopoietic progenitor kinase 1 (HPK1), a negative regulator of T cell receptor signaling, plays a crucial role in multiple cellular immune responses. Emerging researches have demonstrated that inhibiting HPK1 kinase function enhances T cells' ability to recognize tumor antigens and boosts anti-tumor immune responses. As a result, HPK1 has become a promising target for tumor immunotherapy. Herein, we report the design, synthesis, and biological evaluation of a series of novel HPK1 inhibitors featuring a 3-cyano-quinoline scaffold. Among these, compound 3a was identified as the most potent HPK1 inhibitor (HPK1 IC₅₀ = 48 nM). It effectively inhibited SLP76 phosphorylation, enhanced IL-2 cytokine secretion, and reversed PGE2-induced immunosuppression in Jurkat cells. In addition, compound 3a exhibited favorable metabolic stability in mouse liver microsomes and plasma. Overall, this work provides a structurally novel lead compound for the development of HPK1 inhibitors.

项与 HPK1 Inhibitor(Curadev Pharma ) 相关的新闻（医药）

2024-03-12

·BioSpace

Nimbus Therapeutics Appoints Katharine Knobil, M.D., to Board of Directors

BOSTON--(BUSINESS WIRE)-- Nimbus Therapeutics, LLC (“Nimbus Therapeutics” or “Nimbus”), a biotechnology company that designs and develops breakthrough medicines for patients through its powerful computational drug discovery engine, today announced that Katharine Knobil, M.D., has been appointed to the Company’s Board of Directors. Dr. Knobil is a seasoned executive with more than 20 years of experience in pharmaceutical research and product development including global clinical research, medical affairs, and patient safety. “We are honored to welcome Dr. Knobil to our Board of Directors as we embark on the next exciting chapter at Nimbus with plans to accelerate and expand our development programs in multiple therapeutic areas including oncology, immunology, and metabolism. Her leadership and breadth of expertise across clinical development at both small biotechnology and large pharmaceutical companies, including progressing several therapies through to commercialization, will be invaluable as we advance our programs into the clinic,” said Jeb Keiper, M.S., MBA, Chief Executive Officer of Nimbus. “We look forward to working closely with Dr. Knobil to achieve our vision of bringing novel, clinically proven small molecules to millions of patients in need.” Dr. Knobil has led multiple research and development efforts that have resulted in regulatory approvals and launches of several commercial therapies. She most recently served as Chief Medical Officer at Agilent Technologies, where she established an industry-leading medical affairs organization and was responsible for integrating the voice of patients into business and clinical development strategy and decision-making. Previously, she was Chief Medical Officer and Head of Research and Development at Kaleido Biosciences. Before that, Dr. Knobil spent more than 20 years at GlaxoSmithKline (GSK) in roles of increasing responsibility, most recently serving as Chief Medical Officer. In this role, she led medical governance across the pharmaceutical, vaccines, and consumer business units. Her responsibilities also included evidence generation to support the value of new therapies for patients, healthcare providers and payers. Dr. Knobil is currently a member of the Board of Directors at Marker Therapeutics (NASDAQ: MRKR) and Pliant Therapeutics (NASDAQ: PLRX). She earned her B.A. in biology from Cornell University, an M.D. from the University of Texas Southwestern Medical School, and completed her residency at the University of Michigan Medical School and her fellowship in pulmonary and critical care medicine at Johns Hopkins University School of Medicine. “Nimbus has built a robust R&D organization that has demonstrated continued success in advancing promising discovery-stage science to product development. The recent acquisition of the company’s TYK2 inhibitor program by Takeda further reinforces the strength of their unique business model and powerful drug discovery approach. I am excited to join the team, especially given their track record and significant potential to deliver novel medicines that target the underlying causes of many difficult-to-treat diseases,” said Dr. Knobil. “I look forward to partnering with the executive leadership team and other members of the Board to help drive continued progress in pipeline development and initiation of new clinical programs.” About Nimbus Therapeutics Nimbus Therapeutics is a clinical-stage, structure-based drug discovery company developing novel small molecule medicines designed to act against well-validated but difficult-to-drug targets implicated in multiple human diseases. The company advances promising research based on a unique strategy that combines leading-edge computational technologies with a tailored array of machine learning-based predictive modeling approaches. Nimbus’ pipeline includes a clinical-stage HPK1 inhibitor for the treatment of cancer (NCT05128487), as well as a diverse portfolio of preclinical programs focused on cancer, autoimmune conditions, and metabolic diseases. The company is headquartered in Boston, Mass. To learn more about Nimbus, please visit .

高管变更并购

2024-03-07

·BioSpace

Cyclacel Pharmaceuticals Announces Preclinical Proof-of-Concept Data for Fadraciclib to be Presented at the American Association for Cancer Research (AACR) Annual Meeting 2024

BERKELEY HEIGHTS, N.J., March 07, 2024 (GLOBE NEWSWIRE) -- Cyclacel Pharmaceuticals Inc. (NASDAQ: CYCC, NASDAQ: CYCCP; "Cyclacel" or the "Company"), a biopharmaceutical company developing innovative medicines based on cancer cell biology, today announced that preclinical proof-of-concept data with the Company’s fadraciclib will be presented at the upcoming American Association for Cancer Research (AACR) Annual Meeting 2024, being held April 5-10 in San Diego, California. The data will be presented at three poster sessions and report activity and antitumor effects of fadraciclib in biliary tract cancer, lung cancer, Richter transformation and lymphoma cell lines. Details of the presentations are as follows: Title: The CDK2/9 inhibitor fadraciclib is active in Richter transformation and lymphoma cell lines by targeting both cell survival and proliferation Abstract No: 518 / 15 Session Topic: Session PO.ET05.01 - Cell Cycle, Transcription Regulation, and Anticancer Drug Action Date and Time: April 7, 2024, 1:30 PM - 5:00 PM PT Location: Exhibition Hall, Section 21 Title: Elucidation of the fates of CDK2 inhibited aneuploid and residual lung cancers Abstract No: 2117 / 8 Session Topic: Session PO.ET07.02 - Pharmacodynamic Biomarkers of Drug Response Date and Time: April 8, 2024, 9:00 AM - 12:30 PM PT Location: Exhibition Hall, Section 30 Title: Anti-tumor effects of fadraciclib, CDK2/9 inhibitor, in biliary tract cancer Abstract No: 5711 / 11 Session Topic: Session PO.MCB01.01 - Pharmacologic Targeting of Cell Cycle Proteins Date and Time: April 9, 2024, 1:30 PM - 5:00 PM PT Location: Exhibition Hall, Section 18 About Cyclin-Dependent Kinases and Fadraciclib Cyclin-dependent kinases (CDKs) are critical for cell cycle control and transcriptional regulation. Dysregulated CDKs have been linked to the cancer hallmarks of uncontrolled proliferation and increased cancer cell survival. Fadraciclib is a highly selective, potent, orally and intravenously available, next generation inhibitor of CDK2 and CDK9. By inhibiting CDK2 and CDK9 fadraciclib causes apoptotic death through anaphase catastrophe of cancer cells at sub-micromolar concentrations. To date single agent activity, including CR, PR and SD, has been observed in patients with advanced endometrial, squamous NSCLC lung cancer and T-cell lymphoma. Encouraging signals of activity were observed in patients with advanced cervical, hepatocellular, ovarian and pancreatic cancers. 065-101 Study of Oral Fadraciclib Oral fadraciclib is being tested in a Phase 1/2 trial for the treatment of advanced solid tumors and lymphoma (065-101; NCT#04983810). A total of 29 patients have been treated as monotherapy in this ongoing study. The study is enrolling unselected, all comer patients with advanced solid tumors and lymphoma. The Phase 2 part of the 065-101 study is designed to further evaluate fadra safety and efficacy in up to 8 cohorts defined by histology and/or NGS. The study is powered to demonstrate response in the molecular subtype suggested by the Phase 1 data and others that may be sensitive. CDKN2A, CDKN2B, MTAP deletions CDKN2A gene deletions occur in over 40% of several solid tumors, including glioma, head and neck, pancreatic, esophageal, lung (incl. squamous), bladder, melanoma, and others. CDKN2B deletions occur in over 30% of several solid tumors, including bladder, glioma, pancreatic, esophageal, lung (incl. squamous), head and neck, melanoma, and others. MTAP deletions occur in over 25% of several solid tumors, including glioma, mesothelioma, pancreatic, bladder, esophageal and others. MTAP deletion confers dependency on the PRMT5 enzyme in cancer cells which was identified as a synthetic lethal target for MTAP deleted cancers. About Cyclacel Pharmaceuticals, Inc. Cyclacel is a clinical-stage, biopharmaceutical company developing innovative cancer medicines based on cell cycle, transcriptional regulation and mitosis biology. The transcriptional regulation program is evaluating fadraciclib, a CDK2/9 inhibitor, and the anti-mitotic program CYC140, a PLK1 inhibitor, in patients with both solid tumors and hematological malignancies. Cyclacel's strategy is to build a diversified biopharmaceutical business based on a pipeline of novel drug candidates addressing oncology and hematology indications. For additional information, please visit . Forward-looking Statements This news release contains certain forward-looking statements that involve risks and uncertainties that could cause actual results to be materially different from historical results or from any future results expressed or implied by such forward-looking statements. Such forward-looking statements include statements regarding, among other things, the efficacy, safety and intended utilization of Cyclacel’s product candidates, the conduct and results of future clinical trials, plans regarding regulatory filings, future research and clinical trials and plans regarding partnering activities. Factors that may cause actual results to differ materially include the risk that product candidates that appeared promising in early research and clinical trials do not demonstrate safety and/or efficacy in larger-scale or later clinical trials, trials may have difficulty enrolling, Cyclacel may not obtain approval to market its product candidates, the risks associated with reliance on outside financing to meet capital requirements, the potential effects of the COVID-19 pandemic, and the risks associated with reliance on collaborative partners for further clinical trials, development and commercialization of product candidates. You are urged to consider statements that include the words "may," "will," "would," "could," "should," "believes," "estimates," "projects," "potential," "expects," "plans," "anticipates," "intends," "continues," "forecast," "designed," "goal," or the negative of those words or other comparable words to be uncertain and forward-looking. For a further list and description of the risks and uncertainties the Company faces, please refer to our most recent Annual Report on Form 10-K and other periodic and other filings we the Securities and Exchange Commission and are available at . Such forward-looking statements are current only as of the date they are made, and we assume no obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise. Contacts Company: Paul McBarron, (908) 517-7330, pmcbarron@cyclacel.com Investor Relations: Grace Kim, IR@cyclacel.com © Copyright 2024 Cyclacel Pharmaceuticals, Inc. All Rights Reserved. The Cyclacel logo and Cyclacel® are trademarks of Cyclacel Pharmaceuticals, Inc.

临床2期临床1期AACR会议

2024-03-06

·GlobeNewswire-Health Care

Cyclacel Pharmaceuticals Announces Receipt of $2.9 Million R&D Tax Credit

BERKELEY HEIGHTS, N.J., March 06, 2024 (GLOBE NEWSWIRE) -- Cyclacel Pharmaceuticals, Inc. (NASDAQ: CYCC, NASDAQ: CYCCP; "Cyclacel" or the "Company"), a biopharmaceutical company developing innovative medicines based on cancer cell biology, announced that it received £2.3 million (approximately $2.9 million) as a research & development (R&D) tax credit from HMRC, the tax agency of the United Kingdom government. The tax credit is based on R&D costs incurred in the year ended December 31, 2023. The Company expects to receive an additional approximately $0.8 million following confirmation of a change in the rate of tax credit regarding 2023 expenditures. “The R&D tax credit has been an important source of non-dilutive capital supporting Cyclacel’s programs. We appreciate this governmental support as we evaluate potential precision medicine approaches for both our clinical candidates, oral fadraciclib and oral plogosertib, to address oncology indications with large unmet medical needs,” said Paul McBarron, Executive Vice President, Finance & Chief Operating Officer. About Cyclacel Pharmaceuticals, Inc. Cyclacel is a clinical-stage, biopharmaceutical company developing innovative cancer medicines based on cell cycle, transcriptional regulation, epigenetics and mitosis biology. The transcriptional regulation program is evaluating fadraciclib, a CDK2/9 inhibitor, and the epigenetic/anti-mitotic program plogosertib, a PLK1 inhibitor, in patients with both solid tumors and hematological malignancies. Cyclacel's strategy is to build a diversified biopharmaceutical business based on a pipeline of novel drug candidates addressing oncology and hematology indications. For additional information, please visit www.cyclacel.com. Contacts Company:Paul McBarron, (908) 517-7330, pmcbarron@cyclacel.comInvestor Relations:Grace Kim, IR@cyclacel.com © Copyright 2024 Cyclacel Pharmaceuticals, Inc. All Rights Reserved. The Cyclacel logo and Cyclacel® are trademarks of Cyclacel Pharmaceuticals, Inc.

100 项与 HPK1 Inhibitor(Curadev Pharma ) 相关的药物交易

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