Pharmacological Features and Therapeutic Implications of Plumbagin in Cancer and Metabolic Disorders: A Narrative Review.

Plumbagin (PLB) is a naphthoquinone extracted from Plumbago indica. In recent times, there has been a growing body of evidence suggesting the potential importance of naphthoquinones, both natural and artificial, in the pharmacological world. Numerous studies have indicated that PLB plays a vital role in combating cancers and other disorders. There is substantial evidence indicating that PLB may have a significant role in the treatment of breast cancer, brain tumours, lung cancer, hepatocellular carcinoma, and other conditions. Moreover, its potent anti-oxidant and anti-inflammatory properties offer promising avenues for the treatment of neurodegenerative and cardiovascular diseases. A number of studies have identified various pathways that may be responsible for the therapeutic efficacy of PLB. These include cell cycle regulation, apoptotic pathways, ROS induction pathways, inflammatory pathways, and signal transduction pathways such as PI3K/AKT/mTOR, STAT3/PLK1/AKT, and others. This review aims to provide a comprehensive analysis of the diverse pharmacological roles of PLB, examining the mechanisms through which it operates and exploring its potential applications in various medical conditions. In addition, we have conducted a review of the various formulations that have been reported in the literature with the objective of enhancing the efficacy of the compound. However, the majority of the reviewed data are based on in vitro and in vivo studies. To gain a comprehensive understanding of the safety and efficacy of PLB in humans and to ascertain its potential integration into therapeutic regimens for cancer and chronic diseases, rigorous clinical trials are essential. Finally, by synthesizing current research and identifying gaps in knowledge, this review seeks to enhance our understanding of PLB and its therapeutic prospects, paving the way for future studies and clinical applications.

Recent advancement in understanding of Alzheimer's disease: Risk factors, subtypes, and drug targets and potential therapeutics.

Alzheimer's disease (AD) is a significant neocortical degenerative disorder characterized by the progressive loss of neurons and secondary alterations in white matter tracts. Understanding the risk factors and mechanisms underlying AD is crucial for developing effective treatments. The risk factors associated with AD encompass a wide range of variables, including gender differences, family history, and genetic predispositions. Additionally, environmental factors such as air pollution and lifestyle-related conditions like cardiovascular disease, gut pathogens, and liver pathology contribute substantially to the development and progression of AD and its subtypes. This review provides current update and deeper insights into the role of diverse risk factors, categorizing AD into its distinct subtypes and elucidating their specific pathophysiological mechanisms. Unlike previous studies that often focus on isolated aspects of AD, our review integrates these factors to offer a comprehensive understanding of the disease. Furthermore, the review explores a variety of drug targets linked to the neuropathology of different AD subtypes, highlighting the potential for targeted therapeutic interventions. We further discussed the novel therapeutic options and categorized them according to their targets. The roles of different drug targets were comprehensively studied, and the mechanism of action of their inhibitors was discussed in detail. By comprehensively covering the interplay of risk factors, subtype differentiation, and drug targets, this review provides a deeper understanding of AD and suggests directions for future research and therapeutic strategies.

Investigating underlying molecular mechanisms, signaling pathways, emerging therapeutic approaches in pancreatic cancer.

Pancreatic adenocarcinoma, a clinically challenging malignancy constitutes a significant contributor to cancer-related mortality, characterized by an inherently poor prognosis. This review aims to provide a comprehensive understanding of pancreatic adenocarcinoma by examining its multifaceted etiologies, including genetic mutations and environmental factors. The review explains the complex molecular mechanisms underlying its pathogenesis and summarizes current therapeutic strategies, including surgery, chemotherapy, and emerging modalities such as immunotherapy. Critical molecular pathways driving pancreatic cancer development, including KRAS, Notch, and Hedgehog, are discussed. Current therapeutic strategies, including surgery, chemotherapy, and radiation, are discussed, with an emphasis on their limitations, particularly in terms of postoperative relapse. Promising research areas, including liquid biopsies, personalized medicine, and gene editing, are explored, demonstrating the significant potential for enhancing diagnosis and treatment. While immunotherapy presents promising prospects, it faces challenges related to immune evasion mechanisms. Emerging research directions, encompassing liquid biopsies, personalized medicine, CRISPR/Cas9 genome editing, and computational intelligence applications, hold promise for refining diagnostic approaches and therapeutic interventions. By integrating insights from genetic, molecular, and clinical research, innovative strategies that improve patient outcomes can be developed. Ongoing research in these emerging fields holds significant promise for advancing the diagnosis and treatment of this formidable malignancy.

Insights into the preventive actions of natural compounds against Klebsiella pneumoniae infections and drug resistance.

Klebsiella pneumoniae is a type of Gram-negative bacteria that causes a variety of infections, including pneumonia, bloodstream infections, wound infections, and meningitis. The treatment of K. pneumoniae infection depends on the type of infection and the severity of the symptoms. Antibiotics are generally used to treat K. pneumoniae infections. However, some strains of K. pneumoniae have become resistant to antibiotics. This comprehensive review examines the potential of natural compounds as effective strategies against K. pneumonia infections. The alarming rise in antibiotic resistance underscores the urgent need for alternative therapies. This article represents current research on the effects of diverse natural compounds, highlighting their anti-microbial and antibiofilm properties against K. pneumonia. Notably, compounds such as andrographolide, artemisinin, baicalin, berberine, curcumin, epigallocatechin gallate, eugenol, mangiferin, piperine, quercetin, resveratrol, and thymol have been extensively investigated. These compounds exhibit multifaceted mechanisms, including disruption of bacterial biofilms, interference with virulence factors, and augmentation of antibiotic effectiveness. Mechanistic insights into their actions include membrane perturbation, oxidative stress induction, and altered gene expression. While promising, challenges such as limited bioavailability and varied efficacy across bacterial strains are addressed. This review further discusses the potential of natural compounds as better alternatives in combating K. pneumonia infection and emphasizes the need for continued research to harness their full therapeutic potential. As antibiotic resistance persists, these natural compounds offer a promising avenue in the fight against K. pneumonia and other multidrug-resistant pathogens.

The role of serum and glucocorticoid-regulated kinase 1 in cellular signaling: Implications for drug development.

Serum and glucocorticoid-regulated kinase 1 (SGK1) is a ubiquitously expressed protein belonging to the Ser/Thr kinase family. It regulates diverse physiological processes, including epithelial sodium channel activity, hypertension, cell proliferation, and insulin sensitivity. Due to its significant role in the pathogenesis of numerous diseases, SGK1 can be exploited as a potential therapeutic target to address challenging health problems. SGK1 is associated with the development of obesity, and its overexpression enhances the sodium-glucose co-transporter 1 activity, which absorbs intestinal glucose. This review highlighted the detailed functional significance of SGK1 signaling and role in different diseases and subsequent therapeutic targeting. We aim to provide deeper mechanistic insights into understanding the pathogenesis and recent advancements in the SGK1 targeted drug development process. Small-molecule inhibitors are being developed with excellent binding affinity and improved SGK1 inhibition with desired selectivity. We have discussed small molecule inhibitors designed explicitly as potent SGK1 inhibitors and their therapeutic implications in various diseases. We further addressed the therapeutic potential and mechanism of action of these SGK1 inhibitors and provided a strong scientific foundation for developing effective therapeutics.

Comprehensive Insights into Biological Roles of Rosmarinic Acid: Implications in Diabetes, Cancer and Neurodegenerative Diseases.

Phytochemicals are abundantly occurring natural compounds extracted from plant sources. Rosmarinic acid (RA) is an abundant phytochemical of Lamiaceae species with various therapeutic implications for human health. In recent years, natural compounds have gained significant attention as adjuvant and complementary therapies to existing medications for various diseases. RA has gained popularity due to its anti-inflammatory and antioxidant properties and its roles in various life-threatening conditions, such as cancer, neurodegeneration, diabetes, etc. The present review aims to offer a comprehensive insight into the multifaceted therapeutic properties of RA, including its potential as an anticancer agent, neuroprotective effects, and antidiabetic potential. Based on the available evidences, RA could be considered a potential dietary component for treating various diseases, including cancer, diabetes and neurodegenerative disorders.

Therapeutic targeting of microtubule affinity-regulating kinase 4 in cancer and neurodegenerative diseases.

Microtubule affinity-regulating kinase 4 (MARK4) is a member of the Ser/Thr protein kinase family, phosphorylates the microtubule-connected proteins and plays a vital role in causing cancers and neurodegenerative diseases. This kinase modulates multiple signaling pathways, including mammalian target of rapamycin, nuclear factor-κB, and Hippo-signaling, presumably responsible for cancer and Alzheimer's. MARK4 acts as a negative controller of the Hippo-kinase cassette for promoting YAP/TAZ action, and the loss of MARK4 detains the tumorigenic properties of cancer cells. MARK4 is involved in tau hyperphosphorylation that consequently affects neurodegeneration. MARK4 is a promising drug target for cancer, diabetes, and Alzheimer's. Developing the potent and selective inhibitors of MAKR4 are promising in the therapeutic management of associated diseases. Despite its great significance, a few reviews are available to discuss its structure, function and clinical significance. In the current review, we aimed to provide detailed information on the structural features of MARK4 targeted in drug development and its role in various signaling pathways related to cancer and neurodegenerative diseases. We further described the therapeutic potential of MARK4 inhibitors in preventing numerous diseases. Finally, the updated information on MARK4 will be helpful in the further development of effective therapeutic molecules.

Structure-Based Identification of Natural Compounds as Potential RET-Kinase Inhibitors for Therapeutic Targeting of Neurodegenerative Diseases.

BACKGROUND: Tyrosine-protein kinase receptor Ret (RET), a proto-oncogene, is considered as an attractive drug target for cancer and neurodegenerative diseases, including Alzheimer's disease (AD). OBJECTIVE: We aimed to identify potential inhibitors of RET kinase among natural compounds present in the ZINC database. METHODS: A multistep structure-based virtual screening approach was used to identify potential RET kinase inhibitors based on their binding affinities, docking scores, and interactions with the biologically important residues of RET kinase. To further validate the potential of these compounds as therapeutic leads, molecular dynamics (MD) simulations for 100 ns were carried out and subsequently evaluated the stability, conformational changes, and interaction mechanism of RET in-complex with the elucidated compounds. RESULTS: Two natural compounds, ZINC02092851 and ZINC02726682, demonstrated high affinity, specificity for the ATP-binding pocket of RET and drug-likeness properties. The MD simulation outputs indicated that the binding of both compounds stabilizes the RET structure and leads to fewer conformational changes. CONCLUSIONS: The findings suggest that ZINC02092851 and ZINC02726682 may be potential inhibitors for RET, offering valuable leads for drug development against RET-associated diseases. Our study provides a promising avenue for developing new therapeutic strategies against complex diseases, including AD. Identifying natural compounds with high affinity and specificity for RET provides a valuable starting point for developing novel drugs that could help combat these debilitating diseases.

Therapeutic Targeting of Regulated Signaling Pathways of Non-Small Cell Lung Carcinoma.

Non-small cell lung carcinoma (NSCLC) is the most common cancer globally. Phytochemicals and small molecule inhibitors significantly prevent varying types of cancers, including NSCLC. These therapeutic molecules serve as important sources for new drugs that interfere with cellular proliferation, apoptosis, metastasis, and angiogenesis by regulating signaling pathways. These molecules affect several cellular signaling cascades, including p53, NF-κB, STAT3, RAS, MAPK/ERK, Wnt, and AKT/PI3K, and are thus implicated in the therapeutic management of cancers. This review aims to describe the bioactive compounds and small-molecule inhibitors, their anticancer action, and targeting cellular signaling cascades in NSCLC. We highlighted the therapeutic potential of Epigallocatechin gallate (EGCG), Perifosine, ABT-737, Thymoquinine, Quercetin, Venetoclax, Gefitinib, and Genistein. These compounds are implicated in the therapeutic management of NSCLC. This review further offers deeper mechanistic insights into different signaling pathways that could be targeted for NSCLC therapy by phytochemicals and small-molecule inhibitors.

Investigating MARK4 inhibitory potential of Bacopaside II: Targeting Alzheimer's disease.

Microtubule affinity regulating kinase 4 (MARK4) is known to hyperphosphorylate tau protein, which subsequently causes Alzheimer's disease (AD). MARK4 is a well-validated drug target for AD; thus, we employed its structural features to discover potential inhibitors. On the other hand, complementary and alternative medicines (CAMs) have been used for the treatment of numerous diseases with little side effects. In this regard, Bacopa monnieri extracts have been extensively used to treat neurological disorders because of their neuroprotective roles. The plant extract is used as a memory enhancer and a brain tonic. Bacopaside II is a major component of Bacopa monnieri; thus, we studied its inhibitory effects and binding affinity towards the MARK4. Bacopaside II show a considerable binding affinity for MARK4 (K = 107 M-1) and inhibited kinase activity with an IC50 value of 5.4 µM. To get atomistic insights into the binding mechanism, we performed Molecular dynamics (MD) simulation studies for 100 ns. Bacopaside II binds strongly to the active site pocket residues of MARK4 and a number of hydrogen bonds remain stable throughout the MD trajectory. Our findings provide the basis for the therapeutic implication of Bacopaside and its derivatives in MARK4-related neurodegenerative diseases, especially AD and neuroinflammation.

Investigating regulated signaling pathways in therapeutic targeting of non-small cell lung carcinoma.

Non-small cell lung carcinoma (NSCLC) is the most common malignancy worldwide. The signaling cascades are stimulated via genetic modifications in upstream signaling molecules, which affect apoptotic, proliferative, and differentiation pathways. Dysregulation of these signaling cascades causes cancer-initiating cell proliferation, cancer development, and drug resistance. Numerous efforts in the treatment of NSCLC have been undertaken in the past few decades, enhancing our understanding of the mechanisms of cancer development and moving forward to develop effective therapeutic approaches. Modifications of transcription factors and connected pathways are utilized to develop new treatment options for NSCLC. Developing designed inhibitors targeting specific cellular signaling pathways in tumor progression has been recommended for the therapeutic management of NSCLC. This comprehensive review provided deeper mechanistic insights into the molecular mechanism of action of various signaling molecules and their targeting in the clinical management of NSCLC.

Therapeutic targeting of Huntington's disease: Molecular and clinical approaches.

Huntington's disease (HD) is an autosomal dominant ailment that affects a larger population. Due to its complex pathology operating at DNA, RNA, and protein levels, it is regarded as a protein-misfolding disease and an expansion repeat disorder. Despite the availability of early genetic diagnostics, disease-modifying treatments are still missing. Importantly, potential therapies are starting to make their way through clinical trials. Still, clinical trials are ongoing to discover potential drugs to relieve HD symptoms. However, now being aware of the root cause, the clinical studies are focused on molecular therapies to target it. The road to success has not been without bumps since a big phase III trial of tominersen was unexpectedly discontinued due to exceeding risks than drug's benefit to the patients. Although the trial's conclusion was disappointing, there is still cause to be optimistic about what this technique may achieve. We have reviewed the present disease-modifying therapies in clinical development for HD and examined the current landscape of developing clinical therapies. We further investigated the pharmaceutical development of Huntington's medicine in the pharma industries and addressed the existing challenges in their therapeutic success.

A review on regulation of cell cycle by extracellular matrix.

The extracellular matrix (ECM) is a network of structural proteins, glycoproteins and proteoglycans that assists independent cells in aggregating and forming highly organized functional structures. ECM serves numerous purposes and is an essential component of tissue structure and functions. Initially, the role of ECM was considered to be confined to passive functions like providing mechanical strength and structural identity to tissues, serving as barriers and platforms for cells. The doors to understanding ECM's proper role in tissue functioning opened with the discovery of cellular receptors, integrins to which ECM components binds and influences cellular activities. Understanding and utilizing ECM's potential to control cellular function has become a topic of much interest in recent decades, providing different outlooks to study processes involved in developmental programs, wound healing and tumour progression. On another front, the regulatory mechanisms operating to prevent errors in the cell cycle have been topics of a titanic amount of studies. This is expected as many diseases, most infamously cancer, are associated with defects in their functioning. This review focuses on how ECM, through different methods, influences the progression of the somatic cell cycle and provides deeper insights into molecular mechanisms of functional communication between adhesion complex, signalling pathways and cell cycle machinery.

The neuroprotective potential of phytochemicals in traumatic brain injury: mechanistic insights and pharmacological implications.

Traumatic brain injury (TBI) leads to brain damage, comprising both immediate primary damage and a subsequent cascade of secondary injury mechanisms. The primary injury results in localized brain damage, while the secondary damage initiates inflammatory responses, followed by the disruption of the blood-brain barrier, infiltration of peripheral blood cells, brain edema, and the release of various immune mediators, including chemotactic factors and interleukins. TBI disrupts molecular signaling, cell structures, and functions. In addition to physical tissue damage, such as axonal injuries, contusions, and haemorrhages, TBI interferes with brain functioning, impacting cognition, decision-making, memory, attention, and speech capabilities. Despite a deep understanding of the pathophysiology of TBI, an intensive effort to evaluate the underlying mechanisms with effective therapeutic interventions is imperative to manage the repercussions of TBI. Studies have commenced to explore the potential of employing natural compounds as therapeutic interventions for TBI. These compounds are characterized by their low toxicity and limited interactions with conventional drugs. Moreover, many natural compounds demonstrate the capacity to target various aspects of the secondary injury process. While our understanding of the pathophysiology of TBI, there is an urgent need for effective therapeutic interventions to mitigate its consequences. Here, we aimed to summarize the mechanism of action and the role of phytochemicals against TBI progression. This review discusses the therapeutic implications of various phytonutrients and addresses primary and secondary consequences of TBI. In addition, we highlighted the roles of emerging phytochemicals as promising candidates for therapeutic intervention of TBI. The review highlights the neuroprotective roles of phytochemicals against TBI and the mechanistic approach. Furthermore, our efforts focused on the underlying mechanisms, providing a better understanding of the therapeutic potential of phytochemicals in TBI therapeutics.

Microtubule-affinity regulating kinase 4: A potential drug target for cancer therapy.

The human genome encodes more than 500 protein kinases that work by transferring the γ-phosphate group from ATP to serine, threonine, or tyrosine (Ser/Thr/Tyr) residues. Various kinases are associated with the onset of cancer and its further progression. The recent advancements in developing small-molecule kinase inhibitors to treat different cancer types have shown noticeable results in clinical therapies. Microtubule-affinity regulating kinase 4 (MARK-4) is a Ser/Thr protein kinase that relates structurally to AMPK/Snf1 subfamily of the CaMK kinases. The protein kinase modulates major signalling pathways such as NF-κB, mTOR and the Hippo-signalling pathway. MARK4 is associated with various cancer types due to its important role in regulating microtubule dynamics and subsequent cell division. Aberrant expression of MARK4 is linked with several pathologies such as cancer, Alzheimer's disease, obesity, etc. This review provides detailed information on structural aspects of MARK4 and its role in various signalling pathways related to cancer. Several therapeutic molecules were designed to inhibit the MARK4 activity from controlling associated diseases. The review further highlights kinase-targeted drug discovery and development in oncology and cancer therapies. Finally, we summarize the latest findings regarding the role of MARK4 in cancer, diabetes, and neurodegenerative disease path to provide a solid rationale for future investigation and therapeutic intervention.

Structure-guided design and development of cyclin-dependent kinase 4/6 inhibitors: A review on therapeutic implications.

Cyclin-dependent kinase 6 (EC 2.7.11.22) play significant roles in numerous biological processes and triggers cell cycle events. CDK6 controlled the transcriptional regulation. A dysregulated function of CDK6 is linked with the development of progression of multiple tumor types. Thus, it is considered as an effective drug target for cancer therapy. Based on the direct roles of CDK4/6 in tumor development, numerous inhibitors developed as promising anti-cancer agents. CDK4/6 inhibitors regulate the G1 to S transition by preventing Rb phosphorylation and E2F liberation, showing potent anti-cancer activity in several tumors, including HR+/HER2- breast cancer. CDK4/6 inhibitors such as abemaciclib, palbociclib, and ribociclib, control cell cycle, provoke cell senescence, and induces tumor cell disturbance in pre-clinical studies. Here, we discuss the roles of CDK6 in cancer along with the present status of CDK4/6 inhibitors in cancer therapy. We further discussed, how structural features of CDK4/6 could be implicated in the design and development of potential anti-cancer agents. In addition, the therapeutic potential and limitations of available CDK4/6 inhibitors are described in detail. Recent pre-clinical and clinical information for CDK4/6 inhibitors are highlighted. In addition, combination of CDK4/6 inhibitors with other drugs for the therapeutic management of cancer are discussed.

Therapeutic implications and clinical manifestations of thymoquinone.

Thymoquinone (TQ), a natural phytochemical predominantly found in Nigella sativa, has been investigated for its numerous health benefits. TQ showed anti-cancer, anti-oxidant, and anti-inflammatory properties, validated in various disease models. The anti-cancer potential of TQ is goverened by anti-proliferation, cell cycle arrest, apoptosis induction, ROS production, anti-metastasis and anti-angiogenesis, inhibition of cell migration and invasion action. Additionally, TQ exhibited antitumor activity via the modulation of multiple pathways and molecular targets, including Akt, ERK1/2, STAT3, and NF-κB. The present review highlighted the anticancer potential of TQ . We summarize the anti-cancer, anti-oxidant, and anti-inflammatory properties of TQ, focusing on its molecular targets and its promising action in cancer therapy. We further described the molecular mechanisms by which TQ prevents signaling pathways that mediate cancer progression, invasion, and metastasis.

Therapeutic targeting of TANK-binding kinase signaling towards anticancer drug development: Challenges and opportunities.

TANK-binding kinase 1 (TBK1) plays a fundamental role in regulating the cellular responses and controlling several signaling cascades. It regulates inflammatory, interferon, NF-κB, autophagy, and Akt pathways. Post-translational modifications (PTM) of TBK1 control its action and subsequent cellular signaling. The dysregulation of the TBK1 pathway is correlated to many pathophysiological conditions, including cancer, that implicates the promising therapeutic advantage for targeting TBK1. The present study summarizes current updates on the molecular mechanisms and cancer-inducing roles of TBK1. Designed inhibitors of TBK1 are considered a potential therapeutic agent for several diseases, including cancer. Data from pre-clinical tumor models recommend that the targeting of TBK1 could be an attractive strategy for anti-tumor therapy. This review further highlighted the therapeutic potential of potent and selective TBK1 inhibitors, including Amlexanox, Compound II, BX795, MRT67307, SR8185 AZ13102909, CYT387, GSK8612, BAY985, and Domainex. These inhibitors may be implicated to facilitate therapeutic management of cancer and TBK1-associated diseases in the future.

Potential therapeutic targets of Klebsiella pneumoniae: a multi-omics review perspective.

The multidrug resistance developed in many organisms due to the prolonged use of antibiotics has been an increasing global health crisis. Klebsiella pneumoniae is a causal organism for various infections, including respiratory, urinary tract and biliary diseases. Initially, immunocompromised individuals are primarily affected by K. pneumoniae. Due to the emergence of hypervirulent strains recently, both healthy and immunocompetent individuals are equally susceptible to K. pneumoniae infections. The infections caused by multidrug-resistant and hypervirulent K. pneumoniae strains are complicated to treat, illustrating an urgent need to develop novel and more practical approaches to combat the pathogen. We focused on the previously performed high-throughput analyses by other groups to discover several novel enzymes that may be considered attractive drug targets of K. pneumoniae. These targets qualify most of the selection criteria for drug targeting, including an absence of its homolog's gene in the host. The capsule, lipopolysaccharide, fimbriae, siderophores and essential virulence factors facilitate the pathogen entry, infection and survival inside the host. This review discusses K. pneumoniae pathophysiology, including its virulence determinants and further the potential drug targets that might facilitate the discovery of novel drugs and effective treatment regimens shortly.

Identification of Phytoconstituents as Potent Inhibitors of Casein Kinase-1 Alpha Using Virtual Screening and Molecular Dynamics Simulations.

Casein kinase-1 alpha (CK1α) is a multifunctional protein kinase that belongs to the serine/threonine kinases of the CK1α family. It is involved in various signaling pathways associated with chromosome segregation, cell metabolism, cell cycle progression, apoptosis, autophagy, etc. It has been known to involve in the progression of many diseases, including cancer, neurodegeneration, obesity, and behavioral disorders. The elevated expression of CK1α in diseased conditions facilitates its selective targeting for therapeutic management. Here, we have performed virtual screening of phytoconstituents from the IMPPAT database seeking potential inhibitors of CK1α. First, a cluster of compounds was retrieved based on physicochemical parameters following Lipinski's rules and PAINS filter. Further, high-affinity hits against CK1α were obtained based on their binding affinity score. Furthermore, the ADMET, PAINS, and PASS evaluation was carried out to select more potent hits. Finally, following the interaction analysis, we elucidated three phytoconstituents, Semiglabrinol, Curcusone_A, and Liriodenine, posturing considerable affinity and specificity towards the CK1α binding pocket. The result was further evaluated by molecular dynamics (MD) simulations, dynamical cross-correlation matrix (DCCM), and principal components analysis (PCA), which revealed that binding of the selected compounds, especially Semiglabrinol, stabilizes CK1α and leads to fewer conformational fluctuations. The MM-PBSA analysis suggested an appreciable binding affinity of all three compounds toward CK1α.