dovitinib (TKI258) / Novartis, Oncoheroes - LARVOL DELTA

Ex Vivo Drug Sensitivity Evaluation of a ZMYM2: : FGFR1 Fusion-Positive 8p11 Myeloproliferative Syndrome (EMS) Leukemia (ASH 2023) - "Bortezomib and Axitinib exhibited high efficacy on the patient's sample...Other FGFR inhibitors, including Olverematinib, AZD4547, Axitinib, Cediranib, Dovitinib, and Lenvatinib, also demonstrated exquisite sensitivity. Despite extensive screening, no other single agents or drug combinations exhibited increased effectiveness in the ZMYM2: : FGFR1 transformed BaF3 cells except for Trametinib, a MEK inhibitor, and the combination of Belvarafenib (RAF inhibitor) and Gilteritinib (FLT3 inhibitor)... Ex vivo drug sensitivity assays demonstrated the highly selective efficacy of FGFR inhibitors in ZMYM2: : FGFR1 fusion-positive leukemia cells and a fusion-expressing BaF3 cell line. Mutations in the FGFR1 kinase domain (ZMYM2: : FGFR1 F1171L) could contribute to Ponatinib insensitivity. These ex vivo drug screening results provide further support for ongoing clinical trials which are investigating the use of single agent Pemigatinib and other FGFR1 inhibitors for the..."

Preclinical • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Transplantation • FGFR1 • FLT3 • RUNX1 • ZMYM2

Integrating the secretome and interactome to identify novel biomarkers and therapeutic targets in colorectal cancer. (PubMed, Cell Commun Signal) - "This study highlights FGFR4, FLT1, and WNT5A as key diagnostic and therapeutic biomarkers for CRC, with their relevance varying based on the tumor's site of origin. Leveraging these findings, we propose Dovitinib and Nintedanib as promising targeted therapies for CRC. These insights can enhance current treatment strategies and pave the way for future in vivo and in vitro studies, driving progress in CRC research and therapy."

Biomarker • Journal • Colorectal Cancer • Oncology • Solid Tumor • FGFR4 • FLT1

Targeted therapies for Bacillus Calmette-Guerin unresponsive nonmuscle-invasive bladder cancer: a narrative review. (PubMed, Curr Opin Urol) - "The THOR-2 study demonstrated promising results for oral Erdafitinib in 73 high-risk BCG-unresponsive pTa/pT1 patients, showing 6 and 12-month recurrence-free survival rates of 96 and 77%, respectively. However, it was associated with notable adverse events (100%, including 22% serious). Other targeted therapies, such as Dovitinib (FGFR inhibitor), Sunitinib (VEGF inhibitor), and Everolimus (mTOR inhibitor), were assessed in three phase II studies, yielding disease-free survival rates between 8 and 44% over 3-12 months. Additionally, in a recent phase 3 trial involving 134 patients with BCG-unresponsive NMIBC, Oportuzumab Monatox (an EpCAM inhibitor) demonstrated a complete response rate of 40% at 3 months and a median response duration of 9.4 months."

Journal • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

Tyrosine Kinase Inhibitors for Gastrointestinal Stromal Tumor After Imatinib Resistance. (PubMed, Pharmaceutics) - "Sunitinib, regorafenib, and ripretinib are currently approved as standard second-, third-, and fourth-line therapies, each demonstrating efficacy against distinct mutational profiles. Avapritinib, notably effective against PDGFRA D842V mutations, represents a milestone for previously untreatable subgroups. Several alternative agents-such as nilotinib, masitinib, sorafenib, dovitinib, pazopanib, and ponatinib-have shown varying degrees of success in refractory cases or specific genotypes. Investigational compounds, including crenolanib, bezuclastinib, famitinib, motesanib, midostaurin, IDRX-42, and olverembatinib, are under development to address resistant or wild-type GISTs...Future strategies include precision medicine approaches such as ctDNA-guided therapy, rational drug combinations, and novel drug delivery systems to optimize bioavailability and reduce toxicity. Ongoing research will be crucial for refining treatment sequencing and expanding therapeutic options,..."

Journal • Review • Gastrointestinal Cancer • Gastrointestinal Disorder • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • KIT • PDGFRA

Dovitinib Ameliorates Inflammation-Related Diseases by Inhibiting Necroptosis and Ferroptosis. (PubMed, ACS Chem Biol) - "Additionally, Dov inhibited ferroptosis by regulating the NRF2/HMOX1 axis and lipid peroxidation and protected against concanavalin A-induced acute liver injury. Thus, our work revealed that Dov is a dual inhibitor of necroptosis and ferroptosis and provides a potential therapeutic drug or combination approach for treating necroptosis- and ferroptosis-related diseases."

Journal • Hepatology • Immunology • Inflammation • Liver Failure • Oncology • Systemic Inflammatory Response Syndrome • HMOX1 • RIPK1 • TNFA

Molecular Docking and Drug-Likeness of Salicornia-Derived Phytochemicals Against HER Receptors. (PubMed, Curr Issues Mol Biol) - "Among them, 3,5-di-O-caffeoylquinic acid, 3-O-caffeoylquinic acid, myricetin, quercetin, stigmasterol, kaempferol, isorhamnetin, rhamnetin, and hesperitin featured strong predicted binding affinities to the HER1, HER2, and HER4 growth factor receptors, comparable to those of standard anti-cancer drugs such as gefitinib and dovitinib. Further pharmacokinetic assessments, including bioavailability and toxicity analyses, identified compounds with favorable drug-likeness properties and minimal toxicity risks, except for myricetin and quercetin. These findings underscore the potential of Salicornia-derived phytochemicals as promising candidates for the development of safe, novel, and effective anti-cancer agents targeting GFRs, contributing to the advances in precision oncology, pending further validation through in vitro and/or in vivo experiments."

Journal • Oncology • EGFR • ERBB4 • HER-2

Therapeutic targeting of triple-negative breast cancer: A multi-model evaluation of LNA-anti-miR-19b-3p and small molecule inhibitors. (PubMed, Comput Biol Med) - "Additionally, we screened for potential small molecule inhibitors, identifying four promising candidates, including Dovitinib, S-Adenosylmethionine, Guanosine-5',3'-tetraphosphate, and Neomycin, which exhibited favorable drug-like characteristics. In conclusion, our multifaceted approach demonstrates the significant potential of LNA-anti-miR-19b-3p as a therapeutic option for TNBC patients, and the small molecule inhibitors we've uncovered could open new avenues for treating this aggressive form of breast cancer."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ANXA5 • FAT3 • GFOD1 • MIR19B1

Characterization of dovitinib-human serum albumin association potential through optical spectroscopic and in silico approaches. (PubMed, Spectrochim Acta A Mol Biomol Spectrosc) - "Binding place of DTB, as detected by ligand displacement and molecular docking analyses, was found at Sudlow's site I in HSA. The results of the molecular dynamics simulations indicated that the DTB-HSA complex was stable."

Journal • Oncology

Differential Scanning Fluorimetry and compound screening enabled the identification of novel series of microRNA-21 targeting compounds (EACR 2025) - "Selectivity was proven by using as positive control dovitinib, a pre-miR-21 binding molecule that inhibits miR-21 biogenesis... The combination of DSF and screening has identified novel series of pharmacophores acting as pre-miR-21 binders, with the potential to serve as building blocks for the development of lead compounds offering an unconventional modality to target cancer progression."

Oncology • MIR21

IDENTIFICATION OF NOVEL THERAPEUTIC COMPOUNDS FOR THE TREATMENT OF INFANT PATIENTS WITH KMT2A-REARRANGED ACUTE LYMPHOBLASTIC LEUKEMIA BY DRUG REPURPOSING (EHA 2025) - "Additionally, synergistic effects with standard chemotherapy (Vincristine, Dexamethasone, L-Asparaginase; VXL) were assessed.The drug screening identified 119 compounds with selective activity against KMT2Ar iALL while sparing normal cells. This study successfully identified two RTKi as novel therapeutic candidates for KMT2Ar iALL through a drug repurposing approach. Dovitinib and Foretinib have a potent anti-leukemic activity, while sparing healthy cells. Their ability to synergize with standard chemotherapy highlights their potential for clinical application."

Clinical • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • CD34 • CDC37 • KMT2A

Study to Determine the Maximum Tolerated Dose (MTD) of PARPi 2X-121 Monotherapy and the MTD of Dovitinib in Combination With 2X-121 in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=40 | Suspended | Sponsor: Allarity Therapeutics | Trial completion date: Mar 2025 ➔ Dec 2025

Monotherapy • Trial completion date • Oncology • Solid Tumor

FDA-approved drug repurposing screen identifies inhibitors of SARS-CoV-2 pseudovirus entry. (PubMed, Front Pharmacol) - "Pyridoxal 5'-phosphate, Dovitinib, Adefovir dipivoxil, and Biapenem potently inhibit ACE2-dependent viral entry with inhibitory concentration 50% (IC50) values of 57nM, 74 nM, 130 nM, and 183 nM, respectively. We identified four novel FDA-approved candidate drugs for anti-SARS-CoV-2 combination therapy. Our findings contribute to the growing body of evidence supporting drug repurposing as a viable strategy for rapidly developing COVID-19 treatments."

FDA event • Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Allarity Therapeutics Announces Final Settlement with the U.S. Securities and Exchange Commission (GlobeNewswire) - "Allarity Therapeutics, Inc...today announced that it has reached a final settlement with the U.S. Securities and Exchange Commission (SEC) relating to the previously disclosed investigation regarding the Company’s past disclosures concerning its interactions with the U.S. Food and Drug Administration (FDA) regarding its New Drug Application ('NDA') for Dovitinib or Dovitinib-DRP, which was submitted to the FDA in 2021...Under the terms of the settlement, Allarity has consented, without admitting or denying the SEC’s findings, to the entry of an administrative cease-and-desist order. The settlement resolves the SEC’s investigation as to the Company with findings of violations of non-scienter-based provisions under Sections 17(a)(2) and (3) of the Securities Act of 1933, as well as Section 13(a) of the Securities Exchange Act of 1934 and related rules."

Commercial • Oncology • Solid Tumor

Health-related quality of life outcomes in hepatocellular carcinoma patients undergoing systemic therapies: a systematic review (AGW-GESA 2024) - "Eighteen (62%) studies assessed sorafenib and four (14%) studies assessed atezolizumab-bevacizumab (atezo-bev). Of the remaining studies, five (17%) studies investigated PD-1 inhibitors (three pembrolizumab, two nivolumab), two (7%) studied lenvatinib, two (7%) studied ramucirumab, and one study each evaluated cabozantinib, dovitinib, brivanib, regorafenib and durvalumab-tremelimumab... Despite worsening HRQOL outcomes compared to baseline, the first-line agents atezo-bev and lenvatinib improved HRQOL in comparison to sorafenib. Patients on PD-1 inhibitors or nivolumab experienced no change in HRQOL. Sorafenib significantly worsened HRQOL compared to TARE."

Clinical • HEOR • Review • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

Study to Determine the Maximum Tolerated Dose (MTD) of PARPi 2X-121 Monotherapy and the MTD of Dovitinib in Combination With 2X-121 in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=40 | Suspended | Sponsor: Allarity Therapeutics | Trial completion date: Dec 2024 ➔ Mar 2025 | Recruiting ➔ Suspended

Monotherapy • Trial completion date • Trial suspension • Oncology • Solid Tumor

An Ultra-Fast Green UHPLC-MS/MS Method for Assessing the In Vitro Metabolic Stability of Dovitinib: In Silico Study for Absorption, Distribution, Metabolism, Excretion, Metabolic Lability, and DEREK Alerts. (PubMed, Medicina (Kaunas)) - "The DVB and encorafenib (EFB), internal standard, and chromatographic peaks were successfully separated using a reversed phase column (an Eclipse Plus Agilent C8 column) and an isocratic mobile phase. The in vitro half-life (t1/2) and intrinsic clearance (Clint) of DVB were calculated to be 15.48 min and 52.39 mL/min/kg, respectively, which aligned with the findings from the WhichP450 software (version 6.6). Via the usage of in silico software, it has been observed that making small changes to the structure of the aryl piperazine ring and quinolinone moieties, or replacing these groups in the drug design process, shows potential for enhancing the metabolic safety and stability of newly developed derivatives compared to DVB."

Journal • Preclinical • Oncology • Osteosarcoma • Pediatrics • Sarcoma • Solid Tumor

Screening of differential gene expression patterns through survival analysis for diagnosis, prognosis and therapies of clear cell renal cell carcinoma. (PubMed, PLoS One) - "Then we detected 10 repurposable drug molecules (Irinotecan, Imatinib, Telaglenastat, Olaparib, RG-4733, Sorafenib, Sitravatinib, Cabozantinib, Abemaciclib, and Dovitinib.) by molecular docking with KGs-mediated receptor proteins. Their ADME/T analysis and cross-validation with the independent receptors, also supported their potent against ccRCC. Therefore, these outputs might be useful inputs/resources to the wet-lab researchers and clinicians for considering an effective treatment strategy against ccRCC."

Biomarker • Journal • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • CD4 • CD8 • SERPINA5 • SLC2A3

Therapeutic Potental of Quinolin-2H-one Hybrids as Anticancer Agents. (PubMed, Mini Rev Med Chem) - "Tipifarnib and Dovitinib are quinolin-2-one hybrids used to treat cancer, possessing imidazole and benzimidazole heterocyclic rings. The current review presents information on the different quinolin-2-one hybrids and their effect on different cancer cell lines. It also imparts knowledge of the structural requirements for designing novel anticancer agents."

Journal • Gene Therapies • Oncology

Integrative alternative splicing analysis reveals new prognosis signature in B-cell acute lymphoblastic leukemia. (PubMed, Int J Biol Sci) - "More importantly, we conducted in vitro cell proliferation assays to confirm our analysis, demonstrating that the High-18AS cell line (SUP-B15) exhibited significantly enhanced sensitivity to Dasatinib, Dovitinib, and Midostaurin compared to the Low-18AS cell line (REH). These findings reveal AS events as novel prognostic biomarkers and therapeutic targets, advancing personalized treatment strategies in B-ALL management."

IO biomarker • Journal • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology

Oncoheroes Obtains Exclusive Worldwide Oncology Pediatric Rights Of Dovitinib (Oncoheroes Biosciences Press Release) - "Oncoheroes Biosciences...and Novartis have signed a worldwide, exclusive licensing agreement for dovitinib, a multi-tyrosine kinase inhibitor originally developed by Novartis. Under the terms of this agreement, Novartis granted Oncoheroes the exclusive rights to research, develop, and commercialize dovitinib for pediatric oncology indications."

Licensing / partnership • Oncology

Bioinformatics analysis to disclose shared molecular mechanisms between type-2 diabetes and clear-cell renal-cell carcinoma, and therapeutic indications. (PubMed, Sci Rep) - "Finally, sKGs-guided top-ranked three repurposable drug molecules (Digoxin, Imatinib, and Dovitinib) were recommended as the common treatment for both T2D and ccRCC by molecular docking and ADME/T analysis. Therefore, the results of this study may be useful for diagnosis and therapies of ccRCC patients who are also suffering from T2D."

Journal • Clear Cell Renal Cell Carcinoma • Diabetes • Genito-urinary Cancer • Metabolic Disorders • Oncology • Solid Tumor • Type 2 Diabetes Mellitus • CDC42 • CXCL8 • FOXC1 • GATA2 • IL1B • MIR203A • MIR204 • MIR335 • MIR93 • NR2F1 • SCARB1 • TLR2 • TLR4 • YY1

FLT3-PROTACs for combating AML resistance: Analytical overview on chimeric agents developed, challenges, and future perspectives. (PubMed, Eur J Med Chem) - "Next, we explored the latest FLT3-targeting PROTACs developed in the past few years such as quizartinib-based PROTACs, dovitinib-based PROTACs, gilteritinib-based PROTACs, and others. Then, we followed with a deep analysis of their advantages regarding potency improvement and overcoming AML drug resistance. Finally, we discussed the challenges facing these chimeric molecules with proposed future solutions to circumvent them."

Journal • Review • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Targeted Protein Degradation • FLT3

Fibroblast growth factor receptor signaling in estrogen receptor-positive breast cancer: mechanisms and role in endocrine resistance. (PubMed, Front Oncol) - "Current clinical trials, including those evaluating FGFR inhibitors like erdafitinib, lucitanib, and dovitinib, have demonstrated mixed outcomes, underscoring the complexity of FGFR signaling in breast cancer. In conclusion, targeting FGFR signaling in ER+ breast cancer presents both challenges and opportunities. A deeper understanding of the molecular mechanisms and resistance pathways is crucial for the successful integration of FGFR inhibitors into clinical practice, aiming to improve outcomes for patients with endocrine-resistant breast cancer."

Journal • Review • Breast Cancer • Endocrine Cancer • Estrogen Receptor Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • EIF4EBP1 • ER • FGFR • FGFR1 • FGFR2 • FGFR3 • FGFR4 • NSD3

Quantification and analyses of seven tyrosine kinase inhibitors targeting hepatocellular carcinoma in human plasma by QuEChERS and UPLC-MS/MS. (PubMed, J Chromatogr B Analyt Technol Biomed Life Sci) - "Herein, seven TKIs, namely sorafenib tosylate, axitinib, erlotinib, cediranib, brivanib, linifanib, and golvatinib, were successfully analyzed in human plasma by following a quick, easy, cheap, effective, rugged, and safe (QuEChERS) pretreatment method combined with ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS)...In this study, dovitinib was used as the internal standard...The intraday and interday accuracy values ranged from -6.12 % to 7.31 %, with a precision (RSD) of ≤ 10.57 %. The method was rapid, accurate, specific, simple, reproducible, and suitable for the quantitative determination of the seven TKIs in human plasma."

Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

The antihistamine terfenadine inhibits TFE3 dimerization, has antitumor activity and synergizes with tyrosine kinase inhibitors in translocation renal cell carcinoma (AACR 2024) - "The combination of terfenadine with sunitinib showed a synergistic effect in cells endogenously expressing PRCC-TFE3 (IC50=1.5µM; Fraction Affected > 0.05) and NONO-TFE3 (IC50=1.8µM; Fraction Affected0.7). The combination of terfenadine with dovitinib showed a synergistic effect in cells expressing PRCC-TFE3 fusion (IC50=1µM; Fraction Affected>0.4)...This observation underlines the importance of identifying the TFE3 partner gene for targeted therapy. Overall, our results suggest that targeting the dimerization domain along with different oncogenic pathways activated in tRCC cells may represent a new therapeutic approach for this disease."

Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • PRCC • TFE3 • TFEB