Cystic Fibrosis (CF) is a multisystem autosomal recessive disease, caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. The CFTR protein is an ion channel mainly used to regulate the transepithelial movement of anions in mucus secretion tissues, thereby coordinating the balance of salt and fluid levels in mucus secretions. Pathogenic mutations in this gene leading to CF can affect multiple organs including the intestines, pancreas, and liver, with the dysfu

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

Due to their large molecular weight (700-1200Da), poor solubility, and low permeability, PROTAC molecules generally have a low oral bioavailability (F). Therefore, researchers often go to great lengths to increase F, such as optimizing the linker to improve permeability and metabolic stability, selecting E3 ligase ligands with smaller molecular weights, and using prodrug strategies, etc. The structure and bioavailability in various species of ARD-1676The research group of Wang Shaomeng recently

Multiple Myeloma (MM) is a malignant clonal plasma cell disease, accounting for about 10% of malignant tumors of the hematopoietic system. The prognosis of MM varies greatly, it is currently incurable, and most patients still face the problem of recurrence after treatment. With the emergence of new therapies such as immunomodulatory drugs (IMiDs), proteasome inhibitors (PI), and monoclonal antibodies (mAbs), the efficacy of MM has been significantly improved. CD38 is a multifunctional enzyme fo

The KRAS (Kirsten Rat Sarcoma Viral Oncogene Homolog) gene is a GDP/GTP binding protein. KRAS is in the activated state when bound to GTP, and in the deactivated state when bound to GDP. KRAS can be briefly activated by growth factors or tyrosine kinases such as EGFR. The activated KRAS can then activate downstream pathways such as the PI3K-AKT-mTOR pathway, which controls cell generation, and the RAS-RAF-MEK-ERK pathway, which controls cell proliferation. Mutated KRAS becomes continuously activ

JAK2 (Janus kinase 2) is an enzyme that plays a crucial role in the human body, particularly in the regulation of cell growth and differentiation. It is a member of the JAK family of kinases and is primarily involved in the signaling pathway of cytokines and growth factors. JAK2 is responsible for transmitting signals from these molecules to the nucleus of cells, ultimately leading to the activation of various genes involved in cell proliferation and differentiation. Dysregulation or mutations i

The KRAS gene is one of the most commonly mutated oncogenes in tumors and can be detected in various types of malignant tumors, being particularly prevalent in pancreatic cancer (86%), colorectal cancer (41%), and lung cancer (32%). Among all KRAS mutations, G12D (35%), G12V (29%), and G12C (21%) are the most common. KRAS G12D differs from KRAS G12C only in the type of amino acid mutation on the same codon. KRAS G12D is a mutation that introduces an aspartic acid instead of a cysteine at the 12

The JAK molecular family is a key kinase and central node in the cellular signaling pathway within organisms. JAK (Janus kinase) is an important family of non-receptor tyrosine kinases, which includes four subtypes: JAK1, JAK2, JAK3, and TYK2. Its upstream regulators are various types of cell surface receptors of cytokines, and its downstream is signal transducer and activator of transcription (STAT). Its main signaling pathway is: after extracellular cytokines bind to receptors, the JAK coupled

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that commences subtly. Clinically, it is characterized by comprehensive dementia symptoms including memory impairment, aphasia, apraxia, agnosia, impairment of visuospatial skills, executive function disorder, as well as alterations in personality and behavior. The exact etiology of the disease remains unknown to this day. Acetylcholinesterase (AChE) is an essential enzyme found in the human body that plays a crucial role in t

The Cannabinoid receptor 1 (CB1), as one of the most classic receptors of the Endocannabinoid system (ECS), is a G protein-coupled membrane receptor. The CB1 gene is located on chromosome 6q14-q15, containing 4 exons and 3 introns. The encoded CB1 protein is composed of 473 amino acids, with the 117 N-terminal amino acids forming the extracellular region, and the 401-473 C-terminal amino acids forming the intracellular region, with seven transmembrane domains in between. The extracellular region