Trilaciclib Dihydrochloride

CDK4, or cyclin-dependent kinase 4, is a crucial protein involved in cell cycle regulation in the human body. It plays a significant role in controlling the progression of cells from the G1 phase to the S phase, where DNA replication occurs. CDK4 forms a complex with cyclin D, which activates its kinase activity. This activation leads to the phosphorylation of key proteins involved in cell cycle progression, allowing cells to transition from the resting phase to the active phase of cell division. Dysregulation of CDK4 activity has been associated with various diseases, including cancer, making it an important target for pharmaceutical interventions. In ER+ breast cancer, estrogen signaling increases the activity of the ER- cell cycle protein D1-CDK4/6 pathway, driving cells from the G1 phase into the S phase, ultimately leading to uncontrolled cell proliferation. CDK4/6 inhibitors can inhibit the formation of a complex between CDK4/6 and cell cycle protein D, block ATP binding, thus interrupting upstream growth signals and preventing the transition from G1 phase to S phase. The CDK inhibitors currently approved by the FDA are all CDK4/6 inhibitors: Pfizer's Palbociclib (PD-0332991, 21), Novartis's Ribociclib (LEE011, 22), Eli Lilly's Abemaciclib (LY-2835219,23) and G1 Therapeutics' Trilaciclib (G1T28,24). The ATP binding domains of CDK4 and CDK6 exhibit high structural similarity, with differences only between Glu144 (CDK4) and Gln149 (CDK6). These four inhibitors are all ATP-competitive inhibitors, capable of binding with the kinase's ATP binding domain. The analysis of the target CDK4 reveals a competitive landscape with several companies actively involved in the research and development of drugs. Novartis AG and Pfizer Inc. are leading the way with drugs in advanced stages of development. The indications for the target CDK4 primarily focus on breast cancer, with several drugs approved for hormone receptor-positive HER2-negative breast cancer. Small molecule drugs are progressing rapidly, indicating intense competition around innovative drugs. China and the United States are the frontrunners in terms of development, with China showing significant progress. Overall, the target CDK4 presents a promising future in the pharmaceutical industry. How do they work?CDK4 inhibitors are a type of drug that specifically target and inhibit the activity of cyclin-dependent kinase 4 (CDK4). CDK4 is an enzyme that plays a crucial role in regulating the cell cycle, specifically in the transition from the G1 phase to the S phase. By inhibiting CDK4, these inhibitors help to prevent the uncontrolled cell growth and proliferation that is characteristic of cancer. From a biomedical perspective, CDK4 inhibitors are a promising class of drugs in the field of oncology. They have shown potential in the treatment of various types of cancer, including breast cancer, melanoma, and glioblastoma. By blocking the activity of CDK4, these inhibitors can halt the cell cycle progression and induce cell cycle arrest, leading to the inhibition of tumor growth. CDK4 inhibitors are often used in combination with other cancer therapies, such as chemotherapy or targeted therapies, to enhance their effectiveness. They can also be used as single agents in certain cases. These inhibitors are typically administered orally in the form of pills or tablets. It's important to note that CDK4 inhibitors are prescription drugs and should only be used under the supervision of a qualified healthcare professional. They may have side effects, such as nausea, fatigue, and low blood cell counts, which need to be monitored during treatment. Additionally, individual response to CDK4 inhibitors may vary, and not all patients may benefit from this type of therapy. List of CDK4 Inhibitors The currently marketed CDK4 inhibitors include: Trilaciclib Dihydrochloride Dalpiciclib Isethionate AbemaciclibLetrozole/Ribociclib Succinate Ribociclib Succinate Palbociclib Birociclib Lerociclib BEBT-209 BPI-16350 The content above comes from the network. if any infringement, please contact us to modify.

On January 13, Xiansheng Pharmaceutical Group, through its subsidiary Xiansheng Zaiming, announced a collaboration agreement with AbbVie. According to the agreement, AbbVie will obtain licensing options for SIM0500 and will make an upfront payment as well as potential milestone payments of up to $1.055 billion. Additionally, AbbVie will enjoy sales revenue sharing outside of the Greater China region. SIM0500 is a humanized GPRC5D-BCMA-CD3 trispecific antibody developed by Xiansheng Zaiming using its proprietary T-cell engager multispecific antibody technology platform. This drug is currently undergoing Phase I clinical trials for relapsed or refractory multiple myeloma (MM) in both the U.S. and China. As a long-established domestic biopharmaceutical company, Xiansheng Pharmaceutical has cash flow products including Xianbixin, Endu, and Elamod. In the first half of 2024, the company reported an adjusted profit attributable to shareholders of approximately 538 million RMB, an increase of about 144 million RMB compared to approximately 394 million RMB in the same period of 2023, representing a growth rate of about 36.5%. The company's annual net profit target is 1 billion RMB, a 40% increase compared to 2023. Looking back at 2024, several of Xiansheng Pharmaceutical's products have encountered key catalysts, likely ensuring performance in 2025. The sequential therapy composed of Xianbixin sublingual tablets and Xianbixin is expected to peak at 2.5 billion RMB in sales. On December 2, 2024, Xianbixin sublingual tablets were approved for market by the National Medical Products Administration, intended to improve neurological symptoms, daily living activities, and functional impairments caused by acute ischemic stroke. The main results of the Phase III clinical study of Xianbixin sublingual tablets were published in the Journal of the American Medical Association Neurology, demonstrating safety and efficacy in treating acute ischemic stroke. Given that Xianbixin injection sales have exceeded 2 billion RMB, the future potential for Xianbixin sublingual tablets is vast. Enlitone (Situximab β) and Kexaira (Trilaciclib) have successfully entered the National Medical Insurance catalog and are expected to see growth in 2025. Enlitone, as the first domestically produced EGFR-targeted drug, fills the gap for domestically produced EGFR-targeted antibody drugs for colorectal cancer. Kexaira, as the first-of-its-kind short-acting, reversible cyclin-dependent kinase CDK4/6 inhibitor, can temporarily block hematopoietic stem/progenitor cells in G1 phase before chemotherapy, protecting them from the cytotoxic effects of chemotherapeutic agents, thereby enhancing the efficacy of chemotherapy. Established in 2020, Xiansheng Zaiming focuses on the research, development, production, and commercialization of innovative anti-tumor drugs. On February 24, 2024, Xiansheng Pharmaceutical announced that its subsidiary Xiansheng Zaiming completed a 970 million RMB financing round, achieving a post-investment valuation of 8.47 billion RMB. CITIC Investment led the round with 800 million RMB, while Zhongshen New Venture invested 100 million RMB, Xingze Capital contributed 50 million RMB, and Zhonghe Capital invested 20 million RMB. In Xiansheng Zaiming's product pipeline, SIM0500 (CD3/BCMA/GPRC5D) and SIM0505 (CDH6-ADC) are particularly noteworthy. SIM0500 is a humanized GPRC5D-BCMA-CD3 trispecific antibody developed using Xiansheng Zaiming's proprietary T-cell engager multispecific antibody technology platform. This molecule combines a low-affinity high-target-activation CD3 antibody with anti-tumor-associated antibodies to create a T-cell activating drug specifically targeting tumors, exhibiting synergistic effects from multiple antibodies. BCMA and GPRC5D are closely related to the pathogenesis of multiple myeloma, with many CAR-T and TCE therapies associated with this target. Pharmaceutical giant Johnson & Johnson has also shown strong interest in this target combination, developing several CD3 bispecific antibodies and exploring the effects of combination therapy. SIM0500, as one of the top three candidates globally in clinical progress for GPRC5D-BCMA-CD3, completed its first patient enrollment (FPI) in May 2024. Additionally, SIM0500 has obtained FDA fast track designation, significantly enhancing its speed of clinical advancement. SIM0505 (CDH6-ADC) is a CDH6 ADC that is currently still in the preclinical stage. The interest in the CDH6 target has gradually increased in recent years. In 2023, MSD introduced the first ADC targeting CDH6, raludotatug deruxtecan (R-DXd; DS-6000). At the 2023 ESMO, the first ADC updated its Phase I results, showing significant efficacy. In January 2025, Xiansheng Zaiming announced that the CDH6 ADC has been approved for clinical trials in both the U.S. and China. Xiansheng Pharmaceutical's traditional business has shown stable growth, with an adjusted net profit growth rate expected to exceed 40% in 2024. The innovative drug business — Xiansheng Zaiming, having accumulated over several years, is nearing a harvest period. With strong innovation in SIM0500 (CD3/BCMA/GPRC5D) and SIM0505 (CDH6-ADC), this collaboration with AbbVie further validates its innovative strength. We look forward to this well-established pharmaceutical company rejuvenating itself and achieving new heights, leading the way in the industry.