- |||||||||| Biomarker, Journal, Tumor mutational burden, PARP Biomarker: Calcium-dependent adhesion protein CDH18, a potential biomarker for prognosis in uterine corpus endometrial carcinoma. (Pubmed Central) - Feb 28, 2025
In the group with high CDH18 expression, the IC50 values for (5Z)-7-Oxozeaenol, AG-014699, CEP-701, Mitomycin C, PD-0325901, PD-0332991, PHA-665752, SL 0101-1, and SN-38 were notably elevated. CDH18 is a novel promising biomarker in UCEC, uniquely associating tumor progression, immune modulation, and chemotherapy resistance, offering enhanced prognostic accuracy and guiding individualized therapeutic strategies for improved patient outcomes.
- |||||||||| Efficacy of FLT3 Inhibitors in Acute Myeloid Leukemia (AML): A Network Meta-Analysis of Randomized Controlled Trials (LEVEL 3, HALL B3) - Aug 30, 2024 - Abstract #SOHO2024SOHO_436;
Nonsignificant combinations, in decreasing order of effect, were midostaurin + CT + HSCT (HR, 0.8114 [0.5192-1.2681]), sorafenib + CT (HR, 0.8182 [0.6239-1.0730]), gilteritinib + HSCT (HR, 0.8307 [0.5170-1.3348]), sorafenib + HSCT (HR, 0.8834 [0.5367-1.4539]), and lestaurtinib + CT (HR, 0.9056 [0.7642-1.0731]). Our analysis shows that quizartinib + CT + HSCT and gilteritinib + CT significantly reduce mortality risk compared with chemotherapy
- |||||||||| lestaurtinib (CEP-701) / Teva, Kyowa Kirin
Journal, Metastases: Lestaurtinib's antineoplastic activity converges on JAK/STAT signaling to inhibit advanced forms of therapy resistant ovarian cancer. (Pubmed Central) - Jun 19, 2024
In contrast, the most well-known JAK/STAT inhibitor, ruxolitinib, lacked antineoplastic activity against all ovarian cancer cell lines and PDX models tested...Taken together, these findings indicate that lestaurtinib, and other treatments that converge on JAK/STAT signaling, are worthy of further pre-clinical and clinical exploration for the treatment of highly aggressive and advanced forms of ovarian cancer. Lestaurtinib is a novel inhibitor of ovarian cancer, including chemotherapy- and PARPi-resistant models, that acts through robust inhibition of the JAK/STAT pathway and synergizes with standard-of-care agents at clinically relevant concentrations.
- |||||||||| Review, Monotherapy: Efficacy and safety of FLT3 inhibitors in monotherapy of hematological and solid malignancies: a systemic analysis of clinical trials. (Pubmed Central) - Jun 3, 2024
We searched and reviewed clinical trial reports on the monotherapy of 13 FLT3 inhibitors, including sorafenib, lestaurtinib, midostaurin, gilteritinib, quizartinib, sunitinib, crenolanib, tandutinib, cabozantinib, pexidartinib, pacritinib, famitinib, and TAK-659 in patients with hematological and solid malignancies before May 31, 2023...The ORRs of FLT3 inhibitors in hematologic malignancies and solid tumors were 40.8% and 18.8%, respectively, indicating FLT3 inhibitors were more effective for hematologic malignancies than for solid tumors. In addition, time to maximum plasma concentration (Tmax) in these FLT3 inhibitors ranged from 0.7-12.0 hours, but the elimination half-life (T1/2) range was highly variable, from 6.8 to 151.8 h. FLT3 inhibitors monotherapy has shown significant anti-tumor effect in clinic, and the effectiveness may be further improved through combination medication.
- |||||||||| lestaurtinib (CEP-701) / Teva, Kyowa Kirin
Journal: Integrating Transcriptomic and Structural Insights: Revealing Drug Repurposing Opportunities for Sporadic ALS. (Pubmed Central) - Jan 29, 2024
Additionally, docking analysis revealed NOS3 as the gene that interacts with all the short-listed drugs, suggesting its possible involvement in the mechanisms underlying the therapeutic potential of these drugs in sporadic ALS. Overall, our study provides a systematic framework for identifying potential drug candidates for sporadic ALS therapy and highlights the potential of drug repurposing as a promising strategy for discovering new therapies for neurodegenerative diseases.
- |||||||||| Review, Journal: Novel janus-kinase (JAK) inhibitors in myelofibrosis. (Pubmed Central) - Nov 7, 2023
This review includes the current status of JAKi treatment for myelofibrosis, mainly focusing on investigational JAKis; jaktinib, lestaurtinib, itacitinib, gandotinib, BMS-911543, ilginatinib, TQ05105, and flonoltinib maleate...In patients with myelofibrosis, momelotinib was effective in treating anemia, whereas jaktinib was effective in both anemia and Total Symptom Score (TSS)...The increasing variety of JAKis will allow for more personalized treatment options for myelofibrosis in the future. The potential impact on disease progression, molecular responses, and the duration of this response will become important parameters for future evaluations of these drugs.
- |||||||||| lestaurtinib (CEP-701) / Teva, Kyowa Kirin
Journal: Cytosolic DNA accumulation promotes breast cancer immunogenicity via a STING-independent pathway. (Pubmed Central) - Nov 5, 2023
The potential impact on disease progression, molecular responses, and the duration of this response will become important parameters for future evaluations of these drugs. This work demonstrated that cytosolic ssDNA accumulation promotes breast cancer immunogenicity and may be a novel therapeutic strategy to improve the efficacy of ICB with minimal toxicities.
- |||||||||| bemcentinib (BGB324) / BerGenBio, repotrectinib (TPX-0005) / BMS
Journal: The promising impact of Bemcentinib and Repotrectinib on sleep impairment in Alzheimer's disease. (Pubmed Central) - Nov 4, 2023
We report Bemcentinib and Repotrectinib, formerly prescribed for cancer, as potential inhibitors of the CK1 ?. Besides their high binding affinity compared to ATP, they can inhibit all ATP-binding sites and alter the tau binding stability.Communicated by Ramaswamy H. Sarma.
- |||||||||| lestaurtinib (CEP-701) / Teva, Kyowa Kirin
Journal: A short-term three dimensional culture-based drug sensitivity test is feasible for malignant bone tumors. (Pubmed Central) - Sep 14, 2023
Of two CDX and six clinical samples of OS and Ewing's sarcoma, DST identified proteasome inhibitors (bortezomib, carfilzomib) and CEP-701 as potentially effective drugs in common. This unique method of in vitro drug testing using 3D-cell cultures is feasible in surgically resected tissues of metastatic malignant bone tumors.
- |||||||||| lestaurtinib (CEP-701) / Teva, Kyowa Kirin
Preclinical testing of lestaurtinib (CEP701) as a single and combination agent for the treatment of Ewing sarcoma (Section 41; Poster Board #18) - Mar 14, 2023 - Abstract #AACR2023AACR_8252;
Additionally, it provides important insights into the role of IMMT in the mechanism underlying mitochondrial activity and angiogenesis development in KIRC, which suggests IMMT as a promising target for the development of new therapies. Our results highlight the in vitro efficacy of lestaurtinib in EwS and warrant further testing in an in vivomodel as a single agent and in combination with doxorubicin.
- |||||||||| Avastin (bevacizumab) / Roche, Lynparza (olaparib) / Merck (MSD), AstraZeneca, lestaurtinib (CEP-701) / Teva, Kyowa Kirin
Investigation of the JAK/STAT signaling pathway in chemotherapy and PARP inhibitor resistant ovarian cancer (Section 13; Poster Board #5) - Mar 14, 2023 - Abstract #AACR2023AACR_7209;
Recently, the use of targeted therapies such as bevacizumab and PARP inhibitors have been shown to improve progression-free survival in a subset of patients...Through an unbiased drug screen, we have identified lestaurtinib as a potent inhibitor of many sensitive and resistant ovarian cancer cell lines and patient derived organoid models...Finally, combining lestuartinib with standard-of-care cisplatin or olaparib (a PARP inhibitor) is shown to be synergistic, indicating that pharmacological inhibition of JAK/STAT signaling has the potential to counteract drug resistance. Ongoing studies are aimed at further understanding the role of JAK/STAT signaling in ovarian cancer, elucidating the mechanistic processes by which STAT1/3 mediate progression of this disease, and identifying the most effective pharmacological strategies to study in possible future clinical trials.
- |||||||||| Rozlytrek (entrectinib) / Roche, lestaurtinib (CEP-701) / Teva, Kyowa Kirin
Journal: The Alternative TrkAIII Splice Variant, a Targetable Oncogenic Participant in Human Cutaneous Malignant Melanoma. (Pubmed Central) - Jan 22, 2023
In contrast, fully spliced TrkA was dysfunctional in A375 cells. The data identify fully spliced TrkA dysfunction as a novel mechanism for reducing melanoma suppression, support a causal relationship between reductive stress, UPR activation, alternative TrkAIII splicing and TrkAIII activation and characterise a targetable oncogenic pro-survival role for TrkAIII in CMM.
- |||||||||| lestaurtinib (CEP-701) / Teva, Kyowa Kirin
Journal, BRCA Biomarker: Lestaurtinib induces DNA damage that is related to estrogen receptor activation. (Pubmed Central) - Jan 10, 2023
Lestaurtinib also increased c-MYC expression, a target gene of ERα signaling, measured by the quantitative PCR method. This data suggests that lestaurtinib acts as a DNA damage inducer that is related to ERα activation.
- |||||||||| Stendra (avanafil) / Vivus, Menarini, Endo, lestaurtinib (CEP-701) / Teva, Kyowa Kirin
Journal: Bioinformatic Exploration of Hub Genes and Potential Therapeutic Drugs for Endothelial Dysfunction in Hypoxic Pulmonary Hypertension. (Pubmed Central) - Dec 10, 2022
To repurpose known and therapeutic drugs, three candidate compounds (procaterol, avanafil, and lestaurtinib) with a high level of confidence were obtained from the CMAP database. Taken together, the identification of these three hub genes, enrichment pathways, and potential therapeutic drugs might have important clinical implications for HPH diagnosis and treatment.
- |||||||||| Ibrance (palbociclib) / Pfizer, lestaurtinib (CEP-701) / Teva, Kyowa Kirin
Journal, IO biomarker: A cellular senescence-related classifier based on a tumorigenesis- and immune infiltration-guided strategy can predict prognosis, immunotherapy response, and candidate drugs in hepatocellular carcinoma. (Pubmed Central) - Dec 3, 2022
Additionally, four putative drugs (palbociclib, JAK3 inhibitor VI, floxuridine, and lestaurtinib) were identified as potential compounds for patients in the TIS-high group...Our study provides comprehensive clues demonstrating the role of novel TIS in predicting HCC prognosis, immunotherapeutic response, and candidate drugs. This work highlights the significance of tumorigenesis- and immune infiltration-related cellular senescence in cancer therapy.
- |||||||||| Real-World Outcomes and Cardiac Implications of FLT3 Inhibitors in Acute Myeloid Leukemia (Hall D (Ernest N. Morial Convention Center)) - Nov 4, 2022 - Abstract #ASH2022ASH_4182;
A careful cardiac history and management of predisposing conditions to serious cardiac events could help improve drug tolerance, morbidity, and mortality. Further studies are required to elucidate the precise mechanisms of increased incidence of cardiac arrythmias and ways to mitigate them.
- |||||||||| doxorubicin hydrochloride / Generic mfg.
Journal: Doxorubicin-Induced TrkAIII Activation: A Selection Mechanism for Resistant Dormant Neuroblastoma Cells. (Pubmed Central) - Oct 1, 2022
The inhibitory effects of lestaurtinib, entrectinib, crizotinib, and LY294002 on the Dox-induced TrkAIII and Akt phosphorylation and resistance confirm roles for TrkAIII and IP3-K consistent with Dox-induced, TrkAIII-mediated pro-survival IP3K/Akt signaling. This mechanism has the potential to select resistant dormant TrkAIII-expressing NB cells, supporting the use of Trk inhibitors during Dox therapy in TrkAIII-expressing NBs.
- |||||||||| Review, Journal: BDNF and its signaling in cancer. (Pubmed Central) - Oct 1, 2022
The aberrant signaling of BDNF is implicated in various cancers. Well-designed clinical trials are needed to clarify the BDNF role in cancer progression and target it as a therapeutic method.
- |||||||||| 7-Hydroxystaurosporine (UCN-01) / National Cancer Institute, lestaurtinib (CEP-701) / Teva, Kyowa Kirin
Journal: Development of actionable targets of multi-kinase inhibitors (AToMI) screening platform to dissect kinase targets of staurosporines in glioblastoma cells. (Pubmed Central) - Aug 22, 2022
As a result, AToMI analysis revealed AKT and mitochondrial pyruvate dehydrogenase kinase PDK1 and PDK4 as kinase targets of staurosporine derivatives UCN-01, CEP-701, and K252a that synergized with PP2A activation across heterogeneous glioblastoma cells. Based on these proof-of-principle results, we propose that the application and further development of AToMI for clinically applicable multi-kinase inhibitors could provide significant benefits in overcoming the challenge of lack of knowledge of the target specificity of multi-kinase inhibitors.
- |||||||||| lestaurtinib (CEP-701) / Teva, Kyowa Kirin
Rational design of pentapeptides to probe co-assembly with hydrophobic drugs | Poster Board #3078 (Hall F2 (McCormick Place Convention Center)) - Aug 9, 2022 - Abstract #ACSFall2022ACS_Fall_3338;
Out of the positive candidates from the screen, two peptides are studied in detail in for their interaction with the drug Lestaurtinib in proof-of-concept biological studies including in-vitro stability and toxicity assays, and in-vivo bio-distribution. We demonstrate that particles can be engineered from rational design and used for therapeutic applications.
- |||||||||| Iclusig (ponatinib) / Takeda, Otsuka, Incyte, lestaurtinib (CEP-701) / Teva, Kyowa Kirin
Journal: Ponatinib, Lestaurtinib and mTOR/PI3K inhibitors are promising repurposing candidates against Entamoeba histolytica. (Pubmed Central) - Mar 23, 2022
Two classes of compounds are most interesting for further investigations: the Bcr-Abl TK inhibitors, with the ponatinib (EC 0.39) as most potent and mTOR or PI3K inhibitors with 8 compounds in clinical development, of which 4 have nanomolar potency. Overall, these are promising candidates and represent a significant advance for drug development against E. histolytica.
- |||||||||| Jakafi (ruxolitinib) / Novartis, Incyte, Avastin (bevacizumab) / Roche, lestaurtinib (CEP-701) / Teva, Kyowa Kirin
Interrogating JAK/STAT signaling in ovarian cancer as a potential oncogenic driver and therapeutic target (Section 24) - Mar 9, 2022 - Abstract #AACR2022AACR_3278;
Recently, the use of targeted therapies such as bevacizumab and PARP inhibitors have been shown to improve progression-free survival...We have identified lestaurtinib as a potent inhibitor of many ovarian cancer cell lines, including platinum and PARP inhibitor resistant models, and patient derived organoid models...For example, ruxolitinib, the only JAK/STAT inhibitor currently in clinical trials for ovarian cancer, failed to inhibit the growth sensitive, platinum resistant or PARP inhibitor resistant cell lines...Further we plan to elucidate the molecular mechanisms by which STAT1 and STAT3 function to support ovarian cancer cell viability and growth, in order to substantially advance our understanding of JAK/STAT signaling in ovarian cancer and to identify the most effective ways to pharmacologically inhibit JAK/STAT signaling in ovarian cancer cells. Outcomes from this work will have both immediate and long-term impacts for our patients and will lay the foundation for future biomarker-driven clinical trials.
- |||||||||| Nexavar (sorafenib) / Bayer, Amgen
Clinical, Journal: Safety of FLT3 inhibitors in patients with acute myeloid leukemia. (Pubmed Central) - Mar 3, 2022
However, there are unique toxicities and drug-drug interactions that need to be resolved. It is necessary to understand the mechanisms of toxicity in order to recognize and manage them adequately.
- |||||||||| lestaurtinib (CEP-701) / Teva, Kyowa Kirin
Journal: Emerging role for the Serum Response Factor (SRF) as a potential therapeutic target in cancer. (Pubmed Central) - Mar 3, 2022
Small-molecule inhibitors of SRF, such as the CCGs series of compounds and lestaurtinib, which could be used as cancer therapeutics, are also discussed...Further understanding of the molecular mechanisms behind the action of SRF could provide a pipeline of novel molecular targets and therapeutic combinations for cancer. Basket clinical trials and the use of SRF immunohistochemistry as companion diagnostics will help testing of these new targets in patients.
- |||||||||| Nexavar (sorafenib) / Bayer, Amgen
Expert Curation of Somatic FLT3 Variants By the Clingen Somatic Hematologic Cancer Taskforce (ClinGen HCT) () - Nov 24, 2021 - Abstract #ASH2021ASH_6830;
Type II FLT3 inhibitors, including sorafenib, ponatinib, and quizartinib, interact with a hydrophobic region directly adjacent to the ATP-binding domain that is only accessible when the receptor is inactive, which prevents receptor activation...Two separate Tier II, Level D Assertions have been submitted for FLT3 -ITD&D839G for its response to pexidartinib and ponatinib, and more evidence is being collected to form an Assertion for FLT3 N676K. The complexity of the prediction of response/resistance associated with FLT3 D839G and N676K supports the importance of evidence-based curation and collection for these variants in the context of the overall mutation profile, disease context and specific FLT3 TKIs to clearly define their clinical impact.
- |||||||||| CC-90009 / BMS
Synergistic Combination Activity of the Novel GSPT1 Degrader CC-90009 in Acute Myeloid Leukemia Models (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_5008;
P1, P1/2
Using a high-throughput combination screen, we identified rational combination partners that synergize with CC-90009 in in vitro and in vivo AML models. Collectively, these results support the clinical evaluation of CC-90009 in combination with FLT3, BCL2, and IDH2 inhibitors to further improve treatment outcomes for patients with AML.
- |||||||||| lestaurtinib (CEP-701) / Teva, Kyowa Kirin
Journal: Pro-myogenic small molecules revealed by a chemical screen on primary muscle stem cells. (Pubmed Central) - Oct 6, 2021
Further exploration of one of these compounds, the RTK inhibitor CEP-701 (also known as lestaurtinib), revealed potent activity on mouse satellite cells both in vitro and in vivo...We provide compelling evidence that certain RTKs, and in particular RET, regulate satellite cell expansion during muscle regeneration. This study demonstrates the power of small molecule screens of even rare adult stem cell populations for identifying stem cell-targeting compounds with therapeutic potential.
- |||||||||| dexamethasone / Generic mfg., cisplatin / Generic mfg.
Journal: Cisplatin-mediated activation of glucocorticoid receptor induces platinum resistance via MAST1. (Pubmed Central) - Sep 1, 2021
Co-treatment with dexamethasone and cisplatin restores cisplatin-resistant tumor growth, whereas addition of the MAST1 inhibitor lestaurtinib abrogates tumor growth while preserving the inhibitory effect of dexamethasone on inflammation in vivo. These findings not only provide insights into the underlying mechanism of GR in cisplatin resistance but also offer an effective alternative therapeutic strategy to improve the clinical outcome of patients receiving platinum-based chemotherapy with GR agonists.
- |||||||||| Nexavar (sorafenib) / Bayer, Amgen
Retrospective data, Review, Journal, Adverse events: FLT3 inhibitors in acute myeloid leukaemia: assessment of clinical effectiveness, adverse events and future research-a systematic review and meta-analysis. (Pubmed Central) - Jun 26, 2021
There are a large number of ongoing trials; therefore, the results of this review are not a fait accompli; thus, is it recommended that the review be updated in a couple of years' time. Given the challenges in extracting the complete data set required to assess clinical effectiveness, it is highly recommended that ongoing and future trials improve transparency and consistency of reporting of all trial outcomes, particularly disease control and adverse events, to enable a global clinical effectiveness assessment.
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