denfivontinib (SKI-G-801) / Oscotec - LARVOL DELTA

Have You Seem Kerstersia gyiorium on the Bench? Reliable Identification Method and Susceptibility Profile (ASM Microbe 2025) - "Susceptibility was obtained by VITEK® 2 AST-GN801 (bioMerieux, Inc.) applying non-fermenter CLSI breakpoints Final identification of K. gyiorium was achieved by WGS...Only 76.92% were susceptible to Aztreonam and 70.59% to Piperacillin/Tazobactam. 88.89% were susceptible to Levofloxacin but 70.37% were resistant to Ciprofloxacin Conclusion K. gyiorium has been frequently isolated from different sources, but only a few reports. Final identification of K. gyiorium was achieved by WGS. All isolates were 100% susceptible to Aminoglycosides, Carbapenems and Tetracyclines. 90% and 96.15% were susceptible to Cefepime and Ceftazidime, respectively."

Infectious Disease • Otorhinolaryngology • Respiratory Diseases

Targeting the ZMYM2-ANXA9 Axis with FLT3 Inhibitor G749 Overcomes Oxaliplatin Resistance in Colorectal Cancer. (PubMed, Biomedicines) - " The ZMYM2-ANXA9 signaling axis drives chemoresistance and tumor progression in CRC. FLT3 inhibition by G749 effectively downregulates ANXA9 and sensitizes tumors to chemotherapy, highlighting a novel therapeutic approach for chemoresistant CRC."

Journal • Colorectal Cancer • Oncology • Solid Tumor • FLT3 • ZMYM2

Discovery of 3-amide-pyrimidine-based derivatives as potential fms-like tyrosine receptor kinase 3 (FLT3) inhibitors for treating acute myelogenous leukemia. (PubMed, Bioorg Med Chem Lett) - "To discover next-generation FLT3 inhibitors and gather additional structure-activity relationship (SAR) information, we performed structural modifications of G-749 (denfivontinib) utilizing structure simplification and scaffold hopping strategies...Furthermore, it significantly reduced reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP), and strongly inhibited FLT3-mediated signaling pathways. These findings, along with the obtained SAR information, provide valuable insights for the further development of FLT3 inhibitors."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • FLT3

Denfivontinib activates effector T-cells through NLRP3-inflammasome, yielding potent anticancer effects by combination with pembrolizumab. (PubMed, Mol Cancer Ther) - "To demonstrate the extent to which our findings reflect clinical results, we analyzed bulk-RNA sequencing data from 21 NSCLC patients undergoing anti-PD-1 immunotherapy. The NLRP3 inflammasome score influenced enhanced immune responses in patient data undergoing anti-PD-1 immunotherapy, suggesting a role for NLRP3 inflammasome in activating immune responses during treatment."

IO biomarker • Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD4 • CD8 • IFNG • NLRP3

PON1, APOE and SDF-1 Gene Polymorphisms and Risk of Retinal Vein Occlusion: A Case-Control Study. (PubMed, Genes (Basel)) - "Genotyping of rs854560 (L55M) and rs662 (Q192R) for the PON1 gene, rs429358 and rs7412 for the APOE gene and rs1801157 [SDF1-3'G(801)A] for SDF-1 gene was performed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method...In conclusion, PON1 192 R allele carriers (QR + RR) were associated with a statistically significantly increased risk of RVO compared to the QQ homozygotes. These findings suggest that the R allele of the PON1 Q192R is likely to play a role as a risk factor for retinal vein occlusion."

Journal • Cardiovascular • Diabetes • Hematological Disorders • Hypertension • Inflammation • Metabolic Disorders • Retinal Vein Occlusion • APOE • CXCL12 • PON1

Comparison of Sulbactam/Durlobactam to Cefiderocol and Ampicillin/Sulbactam Plus Ceftazidime/Avibactam Synergy for Difficult to Treat (DTR) Acinetobacter baumannii Clinical Isolates (ASM Microbe 2024) - "ABDTR is defined as intermediate or resistant to A/S, meropenem and one more antimicrobial from any class. Initial susceptibilities were performed by the AST-GN801 Vitek® 2 card (bioMérieux, Inc)... Sulbactam-durlobactam demonstrated the higher activity against CRAB/DTR A. baumannii isolates when compared to other agents. It showed 89.3% in-vitro susceptibility compared to cefiderocol (63.8%), which is another antimicrobial option for treating CRAB/DTR isolates. Only 1 isolate that was resistant to S/D was susceptible to the synergy activity of ampicillin/sulbactam + ceftazidime avibactam."

Clinical • Infectious Disease

VIM-Carrying Pseudomonas aeruginosa. The Antimicrobial Resistance Nightmare with Few Therapeutic Options (ASM Microbe 2024) - "Susceptibility testing for multiple agents were performed using Vitek®2 AST-GN801 card (bioMérieux) and broth microdilution for cefiderocol (Liofilchem ComASP®)...All isolates were also NS to ciprofloxacin, levofloxacin, and tobramycin. All isolates were susceptible to cefiderocol (CFD) and amikacin (AMK)... A total of 24 blaVIM-producing P. aeruginosa were obtained from the LIS. All isolates were non-susceptible (NS) to the following β-lactams: piperacillin/tazobactam (P/T), imipenem (IMP), meropenem (MPM) and ceftolozane tazobactam (C/T). 58% (n=14) of isolates were non-susceptible to aztreonam (AZT), 88% (n=21) to cefepime and 92% (n=22) to ceftazidime."

Study to Find a Safe and Effective Dose of SKI-G-801 in the Treatment of Patients With Acute Myeloid Leukemia (AML) (clinicaltrials.gov) - P1 | N=14 | Completed | Sponsor: Oscotec Inc. | Unknown status ➔ Completed | N=40 ➔ 14

Enrollment change • Trial completion • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

A Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of SKI-G-801 in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=36 | Active, not recruiting | Sponsor: Oscotec Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Metastases • Monotherapy • Gastrointestinal Cancer • Oncology • Solid Tumor

A Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of SKI-G-801 in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=36 | Recruiting | Sponsor: Oscotec Inc.

Metastases • Monotherapy • New P1 trial • Gastrointestinal Cancer • Oncology • Solid Tumor

In-Vitro Activity of Aztreonam/Avibactam Gradient Strip Compared to Cefiderocol Disk and Aztreonam Plus Ceftazidime/Avibactam Synergy Broth Microdilution against Clin. Isolates of Multidrug Resistant Stenotrophomonas maltophilia (ASM Microbe 2023) - "Trimethoprim-sulfamethoxazole (SXT) is part of the treatment for S. maltophilia infections, however emerging SXT multidrug resistant (MDR) S. maltophilia has made treatment increasingly difficult...MDR S. maltophilia is defined as SXT resistant, tested by the VITEK®2 AST-GN801 card (bioMerieux, Inc.)...ATM-C/A displayed a lower MIC (greater recovery of ATM) over A/A in some isolates. It could be due to the extra potency of ceftazidime present in the synergy BMD."

Preclinical • Infectious Disease • Septic Shock • SLC51B

Incorporation of SKI-G-801, a Novel AXL Inhibitor, With Anti-PD-1 Plus Chemotherapy Improves Anti-Tumor Activity and Survival by Enhancing T Cell Immunity. (PubMed, Front Oncol) - "In this study, we examined the effect of AXL inhibitors on immune activation and tumor growth in TC1 and C3PQ mouse tumor models, in the context of clinical immunotherapy/chemotherapy and maintenance treatment, using an aPD-1 with/without pemetrexed. These results suggest increased infiltration of T cells, consistent with previous studies using AXL inhibitors. It is expected that the results from this study will serve as a stepping stone for clinical research to improve the existing standard of care."

IO biomarker • Journal • Immune Modulation • Inflammation • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • CD86

SKI-G-801, an AXL kinase inhibitor, blocks metastasis through inducing anti-tumor immune responses and potentiates anti-PD-1 therapy in mouse cancer models. (PubMed, Clin Transl Immunology) - "SKI-G-801 significantly suppressed tumor metastasis and growth by enhancing anti-tumor immune responses. Our results suggest that SKI-G-801 has the potential to overcome anti-PD-1 therapy resistance and allow more patients to benefit from anti-PD-1 therapy."

IO biomarker • Journal • Preclinical • Melanoma • Oncology • Solid Tumor • AXL • CD8

G-749 Promotes Receptor Tyrosine Kinase TYRO3 Degradation and Induces Apoptosis in Both Colon Cancer Cell Lines and Xenograft Mouse Models. (PubMed, Front Pharmacol) - "G-749, a potential TAM receptor tyrosine kinase inhibitor, and its derivative SKI-G-801, effectively inhibits the phosphorylation of AXL at nanomolar concentration (IC = 20 nM)...In addition, we demonstrated that G-749 inhibits the signaling pathway associated with cell proliferation in colon cancer cell lines HCT15 and SW620, as well as tumor xenograft mouse models. We propose G-749 as a new therapeutic agent for the treatment of colon cancer caused by abnormal TYRO3 expression or activity."

Journal • Preclinical • Acute Myelogenous Leukemia • Breast Cancer • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Hematological Malignancies • Leukemia • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • Triple Negative Breast Cancer • AXL • FLT3 • TYRO3

[VIRTUAL] Single-cell RNA sequencing reveals priming professional antigen-presenting macrophages and chemokine expressing T cells in tumor microenvironment by AXL inhibitor, SKI-G-801 (AACR 2021) - "A novel AXL inhibitor, SKI-G-801 drives priming of professional antigen-presenting cells and tumor-infiltrating T cells, leading to immunological synapsis for tumor killing, which is significantly enhanced by the combination with pembrolizumab. These results suggest the inhibition of AXL signal pathway by SKI-G-801 could confer a solid rationale for clinical investigation of lung cancer cells."

Biomarker • Tumor microenvironment • Lung Cancer • Oncology • Solid Tumor • CCL4 • CD2 • CD34 • CD8 • GZMA • GZMB • HLA-DRB1 • IL1B

[VIRTUAL] Incorporation of SKI-G-801, novel AXL inhibitor, with anti-PD-1 inhibitor plus chemotherapy improved anti-tumor activity and survival outcome via enhancing anti-tumor T cell immunity (AACR 2021) - "Anti-PD-1(αPD-1) combined with paclitaxel(Pac) / carboplatin(Carbo) and pemetrexed(Pem) / cisplatin(Cis) are standard therapy in non-squamous and squamous lung cancer patients, respectively. Incorporation of SKI-G-801, a novel AXL inhibitor, with αPD-1 combined with chemotherapy significantly improved overall survival and anti-tumor activity in both non-squamous and squamous lung cancer model through enhancing cytotoxicity of CD8+ T cells and memory CD4+ T cells. These findings provide mechanistic insight into the activity of SKI-G-801 combined with standard therapy and support its clinical development in metastatic NSCLC as first line therapy."

Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • CD44 • CD8 • IFNG

[VIRTUAL] Neoadjuvant and adjuvant anti-PD-1 based combination immunotherapy with a novel AXL inhibitor, SKI-G-801 in syngeneic tumor model: A combined analysis of immune profiling (AACR-II 2020) - "This study confirmed that a potential combination with aPD-1 and SKI-G-801 applies to neoadjuvant therapy, as evidenced by increased T cell infiltration and function. Our findings provide a rationale for further clinical investigations."

Oncology • CD44 • IFNG

SKI-G-801, an AXL kinase inhibitor, blocks metastasis and induces anti-tumor immune responses in various syngeneic cancer models (AACR 2019) - "SKI-G-801 demonstrates great potential in anti-cancer activity though immune responses. The anti-cancer effects lead to a reversal of the metastatic phenotype in animal model. Our results suggest that SKI-G-801 is a promising drug for prevention against metastatic cancer."

Preclinical