riviciclib (P27600) / Piramal Phytocare - LARVOL DELTA

Antifungal Activity of 8-Hydroxyquinoline Derivatives Against Candida auris, Candida haemulonii, Cryptococcus neoformans, and Cryptococcus gattii Complex. (PubMed, Pathogens) - "PH276 exhibited synergistic effects with fluconazole and caspofungin against C. haemulonii (FIC ≤ 0.5). In vivo toxicity assays in Tenebrio molitor, Galleria mellonella, and Caenorhabditis elegans revealed no significant adverse effects, with survival rates comparable to controls. These findings highlight PH265 and PH276 as promising antifungal agents with biofilm-disrupting properties, capsule-modulating effects, and low toxicity, supporting their potential for therapeutic development."

Journal • Infectious Disease

Comparative study on selective profiling of cardiovascular and cerebrovascular disease-associated proteins using two statin-based magnetic separation materials. (PubMed, Anal Methods) - "Two first-line lipid-lowering drugs, atorvastatin (AN) and rosuvastatin (RSV), were covalently immobilized onto nanoparticle surfaces to fabricate novel magnetic separation materials, Fe3O4@AN and Fe3O4@RSV...Three proteins (Q3T052, P1276, and Q58D62) were co-enriched by the two materials...Among these, two proteins (P02042 and P14174) were exclusively detected in patient sera, while Q14624 was detectable in CVD patient serum, healthy human serum, and FBS but significantly upregulated in CVD patient serum. Collectively, this protein-drug interaction-based screening strategy exhibits broad applicability and establishes a novel paradigm for rational drug design and development."

Journal • Cardiovascular • CNS Disorders • Respiratory Syncytial Virus Infections • Vascular Neurology

The case of the vanishing CAN (colitis-associated neoplasia) (BSG 2025) - "She was intolerant to mesalazine/azathioprine and initially reluctant to start Infliximab.Surveillance in May 2023 showed a 20mm flat polyp in the splenic flexure (SF)...There was variable loss of MLH1 and null pattern of P53, which further confirmed the diagnosis.Download figure Open in new tab Download powerpoint Abstract P276 Figure 1 Conclusions We present a case of a young patient with clinically indolent IBD and concomitant PSC who benefitted by 'aggressive' medical treatment, as this allowed accurate dysplasia assessment. More importantly, this case demonstrates a challenging histological diagnosis of predominantly non-conventional IBD dysplasia, both visible and invisible, which was initially 'missed' in the resection specimen, despite the biopsy diagnosis of subtle, yet classical, dysplasia features. Pathologists need to be aware of these cytoarchitectural and immunohistochemical features to avoid misdiagnosis and disservice to patients and..."

Clinical • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Oncology • Ulcerative Colitis • MLH1 • SATB2

P276-P290: Trauma Poster Session 2 (AAOS 2025) - No abstract available

Mood Disorders

MCM8-mediated mitophagy protects vascular health in response to nitric oxide signaling in a mouse model of Kawasaki disease. (PubMed, Nat Cardiovasc Res) - "Mice that are deficient in Mcm8, Trim21 and Nos2 or reconstituted with the East-Asian-specific MCM8-P276 variant develop more severe coronary artery vasculopathy in the Lactobacillus casei extract-induced KD model. Collectively, the data suggest that MCM8 protects vascular health in the KD setting."

Journal • Preclinical • Cardiovascular • Targeted Protein Degradation • MCM8 • MCM9 • NOS2 • STING • TRIM21

Computational Modeling to Identify Drugs Targeting Metastatic Castration-Resistant Prostate Cancer Characterized by Heightened Glycolysis. (PubMed, Pharmaceuticals (Basel)) - "Three of the candidates, ivermectin, CNF2024, and P276-00, were selected for subsequent vitro validation based on the highest measured drug responses associated with glycolysis/OXPHOS in pan-cancer cell lines...EEF1B2 and CCNA2 were identified as key biomarkers for ivermectin and CNF2024, respectively, through multiple independent biomarker nomination pipelines. In conclusion, this study offers new efficacious therapeutics beyond traditional androgen-deprivation therapies by precisely targeting mCRPC with high glycolysis."

Journal • Metastases • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor • AR • CCNA2

De novo transcriptome analysis of Dysoxylum binectariferum to unravel the biosynthesis of pharmaceutically relevant specialized metabolites. (PubMed, Front Plant Sci) - "The tropical tree, D. binectariferum, is a prominent source of chromone alkaloid rohitukine, which is used in the semi-syntheses of anticancer molecules such as flavopiridol and P-276-00. Together, the D. binectariferum transcriptome resource forms a basis for further exploration of biosynthetic pathways of these valuable compounds through functional validation of the candidate genes and metabolic engineering in heterologous hosts. Additionally, the transcriptome dataset generated will serve as an important resource for research on functional genomics and enzyme discovery in D. binectariferum and comparative analysis with other Meliaceae family members."

Journal • Oncology

VA.APS.P276. Every Step Counts: Insights From the Latest Research in PAD (AHA 2022) - No abstract available

Cardiovascular

An Overview of CDK Enzyme Inhibitors in Cancer Therapy. (PubMed, Curr Cancer Drug Targets) - "We have mentioned first-generation pan-CDKIs, flavopiridol and roscovitine, as well as second-generation CDKIs, dinaciclib, P276-00, AT7519, TG02, roniciclib, and RGB-286638, based on their research phases, clinical trials, and cancer targeting. CDKIs are CDK4/6, CDK7, CDK9, and CDK12 inhibitors. Finally, we have looked into the efficacy of CDK inhibitors and PD1/PDL1 antibodies when used together, which could lead to the development of a viable cancer treatment strategy."

Journal • Oncology • CDK4 • CDK7 • CDK9

Rohitukine content across the geographical distribution of Dysoxylum binectariferum Hook F. and its natural derivatives as potential sources of CDK inhibitors. (PubMed, Heliyon) - "The chromone alkaloids, majorly rohitukine and its analogues were closely clustered with flavopiridol, P-276-00 and IIIM-290 along with other chrotacumines in the chemical phylogeny. In conclusion, D. binectariferum is a rich source of chromone alkaloids, which could lead to the discovery of more potential scaffolding for CDK inhibitors as anticancer drugs."

Journal • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • CDK1 • CDK15

Transcriptome analysis and differential expression in Arabidopsis thaliana in response to rohitukine (a chromone alkaloid) treatment. (PubMed, Funct Integr Genomics) - "Rohitukine is a chromone alkaloid and precursor of potent anticancer drugs flavopiridol, P-276-00, and 2,6-dichloro-styryl derivative (11d) (IIIM-290). The RNA-seq result was also validated by real-time qRT-PCR analysis. In light of these results, we discuss (i) likely ecological importance of rohitukine in parent plant as well as (ii) comparison between responses to rohitukine treatment in plants and mammals."

Journal • Immune Modulation • Inflammation • Metabolic Disorders • Oncology

Promising Anticancer Activity of Multitarget Cyclin Dependent Kinase Inhibitors against Human Colorectal Carcinoma Cells. (PubMed, Curr Mol Pharmacol) - "This study provides evidence that multitarget CDK inhibitors can serve as promising therapeutic agents against CRC alone or in combination."

Journal • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CDK1 • CDK9

ACNP 60 Annual Meeting: Poster Abstracts P276 - P550. (PubMed, Neuropsychopharmacology) - No abstract available

Journal

Integrated Genomic Profiling and Drug Screening of Patient-Derived Cultures Identifies Individualized Copy Number-Dependent Susceptibilities Involving PI3K Pathway and 17q Genes in Neuroblastoma. (PubMed, Front Oncol) - "Among 1278 significantly correlated gene-drug pairs, copy number of GNA13 and DNA damage response genes CBL, DNMT3A, and PPM1D were most significantly correlated with cytotoxicity; the drugs most commonly associated with these genes were PI3K/mTOR inhibitor PIK-75, and CDK inhibitors P276-00, SNS-032, AT7519, flavopiridol and dinaciclib. Together, our data defined individualized dose-dependent relationships between copy number gains of PI3K and STAT family genes particularly on 17q and susceptibility to PI3K and cell cycle agents in neuroblastoma. Integration of genomic profiling and drug screening of patient-derived models of neuroblastoma can quantitatively define copy number-dependent sensitivities to targeted inhibitors, which can guide personalized therapy for such mutationally quiet cancers."

Journal • Immunology • Neuroblastoma • Oncology • Pediatrics • Solid Tumor • DNMT3A • GNA13 • PPM1D

"PS276 RAS Symposium is happening now!! #ACSCC21 @AmCollSurgeons @RandiRyanMD @kBraselDazzle @daniellis__ @MinterWiscSurg @HPB_Surgeon and Ingrid Woelfel discuss time-based vs competency-based approaches to #SurgEd" (@RASACS)

[VIRTUAL] PS276. RAS Symposium (ACS-CLINCON 2021) - "The Resident and Associate Society–American College of Surgeons Symposium is a pro- and con-style debate where an experienced surgeon and a resident member on each side of an issue present a thoughtful, researched-based point of view. A differrent topic of interest to the surgical community is chosen each year, and an established surgeon serves as the moderator."

CDK inhibitors in cancer therapy, an overview of recent development. (PubMed, Am J Cancer Res) - "We reviewed first-generation pan-CDKIs Flavopiridol and Roscovitine, and second-generation CDKIs Dinaciclib, P276-00, AT7519, TG02, Roniciclib, RGB-286638 by focusing on their developing stages, clinical trials and targeting cancers. These CDKIs include CDK4/6, CDK7, CDK9, and CDK12/13 inhibitors. Finally, the efficacy and discrepancy of combination therapy with CDK inhibitors and PD1/PDL1 antibodies were analyzed, which might give insights into the development of promising strategy for cancer treatment."

Journal • Review • Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • CDK12 • CDK7 • CDK9

[VIRTUAL] PS276 - RAS-ACS Symposium: Resident Unionization: Future of Resident Advocacy or Deterioration of Our Profession? (ACS-CLINCON 2020) - "The Resident or Associate Fellow participants are chosen from a competitive essay contest. Each year, a different topic is selected based on current issues concerning surgery or surgeons."

Nucleic acid binding mechanism of flavone derivative, riviciclib: Structural analysis to unveil anticancer potential. (PubMed, J Photochem Photobiol B) - "The order (10 M) of binding constant for riviciclib-nucleic acid complexation infer moderate to strong affinity of riviciclib with DNA and tRNA, respectively. Molecular docking explorations are further in corroboration with our spectroscopic outcomes."

Journal • Oncology

[VIRTUAL] Medicinal chemistry of natural products to discover kinase inhibitors for cancer: Discovery and preclinical development of IIIM-290 for pancreatic cancer (ACS-Fall 2020) - "This natural product has already inspired the discovery of two clinical candidates flavopiridol and riviciclib, which are potent Cdk inhibitors. The regulatory safety pharmacology (IND-enabling studies: systemic toxicity, mutagenicity, genotoxicity, hERG binding, reproductive toxicity) of the lead have been completed, wherein it was found to possess good profile. This work will present our synthetic strategies, in vitro/ in-vivo efficacy data, ADME studies, preclinical safety and formulation results."

Preclinical • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor

[VIRTUAL] Medicinal chemistry of natural products to discover kinase inhibitors for cancer: Discovery and preclinical development of IIIM-290 for pancreatic cancer (ACS-Fall 2020) - "This natural product has already inspired the discovery of two clinical candidates flavopiridol and riviciclib, which are potent Cdk inhibitors. The regulatory safety pharmacology (IND-enabling studies: systemic toxicity, mutagenicity, genotoxicity, hERG binding, reproductive toxicity) of the lead have been completed, wherein it was found to possess good profile. This work will present our synthetic strategies, in vitro/ in-vivo efficacy data, ADME studies, preclinical safety and formulation results."

Preclinical • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor

Analyst presentation (Piramal Life Sciences) - Anticipated product launch in FY '14

Anticipated product launch • Hematological Malignancies

P276-00, a cyclin-dependent kinase inhibitor, modulates cell cycle and induces apoptosis in both in vitro and in vivo mantle cell lymphoma cell lines (Mol Cancer) - "P276-00 showed a potent cytotoxic effect against MCL cell lines..Most importantly, in vivo studies have revealed significant dose dependent efficacy as a single agent with increased survival period compared to vehicle treated. Further, preliminary combination studies of P276-00 with doxorubicin and bortezomib showed in vitro synergism"

Preclinical • Non-Hodgkin’s Lymphoma

'Urmitella timonensis' gen. nov., sp. nov., 'Blautia marasmi' sp. nov., 'Lachnoclostridium pacaense' sp. nov., 'Bacillus marasmi' sp. nov. and 'Anaerotruncus rubiinfantis' sp. nov., isolated from stool samples of undernourished African children. (PubMed) - New Microbes New Infect - "We report here the main characteristics of five new species 'Urmitella timonensis' strain Marseille-P2918(T) (CSUR P2918), 'Blautia marasmi' strain Marseille-P2377(T) (CSUR P2377), 'Lachnoclostridium pacaense' strain Marseille-P3100(T) (CSUR P3100), 'Bacillus marasmi' strain Marseille-P3556(T) (CSUR P3556) and 'Anaerotruncus rubiinfantis' strain MT15(T) (CSUR P2276), which were isolated recently from stool samples taken from undernourished children in Niger and Senegal using microbial culturomics."

Journal • Biosimilar

Development of a CDK10/CycM in vitro Kinase Screening Assay and Identification of First Small-Molecule Inhibitors. (PubMed, Front Chem) - "We reveal the ability of known CDK inhibitors, among which clinically tested SNS-032, riviciclib, flavopiridol, dinaciclib, AZD4573 and AT7519, to potently inhibit CDK10/CycM. We also show that NVP-2, a strong, remarkably selective CDK9 inhibitor is an equally potent CDK10/CycM inhibitor. Finally, we validate this kinase assay for applications in high-throughput screening campaigns to discover new, original CDK10 inhibitors."

Journal