FAK-JAK 2 dual Inhib / Teva - LARVOL DELTA

Bioactive siRNA-Based Liposomes Promoted Tendon-Bone Healing in Osteoporotic Mice by Recovering the Stemness of CD248+ TSPCs. (PubMed, Adv Sci (Weinh)) - "CD248+ TSPCs displayed reduced proliferation, increased apoptosis, and impaired migration, driven by altered FAK-JAK-STAT1 signaling...This study reveals that elevated CD248 expression negatively impacts TSPC stemness and impairs healing under osteoporotic conditions. Targeting CD248 using si-CD248-loaded liposomes effectively restores TSPC regenerative potential, representing a promising therapeutic strategy to enhance tendon-bone healing in osteoporotic patients."

Journal • Preclinical • Osteoporosis • Rheumatology • STAT1

Osimertinib plus repotrectinib phase I trial in TKI-resistant non-small cell lung cancer (NSCLC) with EGFR mutations. (ASCO 2025) - P1 | "The findings prompted us to carry out the current study with osimertinib plus TPX-0005, which inhibit Src/FAK/JAK2, in addition to ALK, ROS1 and NTRKs. In Part Ia osimertinib + repotrectinib showed impressive intracranial ORR with a manageable safety profile. Part Ib with repotrectinib 160 mg BID plus osimertinib 80 mg is ongoing. Updated results will be presented."

P1 data • Anemia • Fatigue • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • CDK4 • EGFR • FAT1 • FGFR3 • MET • MYC • PIK3CA • ROS1 • STAT3 • TP53 • YAP1

Unraveling the mechanism of the anticancer potential of emodin using 2D and spheroid models of A549 cells. (PubMed, Biochem Biophys Res Commun) - "Molecular docking analysis confirmed the interactions of emodin with JAK2 and FAK. These findings suggest that the JAK2/STAT3 and FAK/ERK signaling pathways may serve as critical drivers of the therapeutic effectiveness of emodin in A549 cells."

Journal • Oncology

Ropotrectinib is a novel polypharmacology kinase inhibitor against WT and mutant ROS1, TRK and ALK (AACR 2018) - P1/2; "...Moreover, ropotrectinib displays inhibitory activity for SRC/FAK/JAK2, rendering its potential to overcome drug resistance caused by by-passing mechanisms such as EMT.Ropotrectinib is a superb ROS1 inhibitor...Acquired secondary mutations in ROS1 kinase domain is a common drug resistance mechanism in 50-60% patients progressed on crizotinib treatment, with solvent front mutations most frequently observed. Compared to other ROS1 inhibitors, such as lorlatinib, ceritinib, brigatinib and entrectinib, ropotrectinb demonstrated most potent activity against WT and mutant ROS1, especially solvent front mutations such as G2032R in cellular assays and potently inhibited xenograft tumors.Ropotrectinib is the most potent TRK inhibitors in clinic, with IC50s < 1nM in cellular assays. Preclinic in vitro and in vivo studies further demonstrated that ropotrectinib overcomes clinical resistance mutations which occur in patients progressed on TRK inhibitors, such as entrectinib and...

Non Small Cell Lung Cancer

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Interferon functional analog activates antiviral Jak/Stat signaling through integrin in an arthropod. (PubMed, Cell Rep) - "Therefore, this study reveals that integrin, as the receptor of MjVago-L, mediates Jak/Stat activation. The establishment of the MjVago-L/integrin/Fak/Jak/Stat/Ficolin axis provides insights into antiviral cytokine signaling in invertebrates."

Journal

[VIRTUAL] Repotrectinib increases effectiveness of MEK inhibitors in KRAS mutant cancer models (AACR 2021) - "However, clinical studies of single agent MEKi or combinations with docetaxel in mutant KRAS NSCLC patients were associated with low response rates...Repotrectinib is a next-generation ROS1/TRK inhibitor with SRC/FAK/JAK2 inhibitory potencies which may suppress adaptive resistance to MEK inhibitors. In the current study, repotrectinib combinations with KRAS signaling network inhibitors including MEK (trametinib, selumetinib), MEK/RAF (VS-6766), ERK (LY3214996), SHP2 (TNO155) were explored...Repotrectinib was shown to suppress molecular mechanisms of adaptive resistance mechanisms to MEK inhibition in preclinical models. These results suggest that the combination of repotrectinib with MEKi can repress the mutant KRAS signaling network to achieve more potent and durable anti-tumor activity and warrants clinical investigation in patients with KRASG12D and KRASG12V mutant cancers."

Preclinical • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • KRAS • MAP2K1

[VIRTUAL] Repotrectinib Increases KRAS-G12C Inhibitor Effectiveness Via Simultaneous Inhibition of SRC, FAK, and JAK2 (AACR-NCI-EORTC 2020) - "KRAS-G12C inhibitors AMG510 and MRTX849 have clinical activity in patients harboring a KRASG12C mutation, however, the durability of response is attenuated by the onset of multiple resistance mechanisms...Repotrectinib/AMG510 suppresses more KRAS signaling nodes than AMG510 combinations with dasatinib, defactinib, or ruxolitinib and therefore affects a broader signaling network... In preclinical studies, simultaneous inhibition of SRC/FAK/JAK2 by repotrectinib has a range of effects that synergize with KRAS-G12C inhibitor pharmacology and suppress mechanisms of resistance. Further investigation for the potential to increase the duration of response for KRAS-G12C inhibitor therapies is warranted."

Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • JAK2 • KRAS • ROS1

[VIRTUAL] Repotrectinib Increases KRAS-G12C Inhibitor Effectiveness Via Simultaneous Inhibition of SRC, FAK, and JAK2 (AACR-NCI-EORTC 2020) - "KRAS-G12C inhibitors AMG510 and MRTX849 have clinical activity in patients harboring a KRASG12C mutation, however, the durability of response is attenuated by the onset of multiple resistance mechanisms...Repotrectinib/AMG510 suppresses more KRAS signaling nodes than AMG510 combinations with dasatinib, defactinib, or ruxolitinib and therefore affects a broader signaling network... In preclinical studies, simultaneous inhibition of SRC/FAK/JAK2 by repotrectinib has a range of effects that synergize with KRAS-G12C inhibitor pharmacology and suppress mechanisms of resistance. Further investigation for the potential to increase the duration of response for KRAS-G12C inhibitor therapies is warranted."

Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • JAK2 • KRAS • ROS1

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[VIRTUAL] Repotrectinib increases effectiveness of MEK inhibitor trametinib in KRAS mutant cancer models via simultaneous SRC/FAK/JAK2 inhibition (AACR-II 2020) - "In contrast, suppression of the trametinib-induced pAKT rebound was not achieved by combinations of trametinib with dasatinib (SRCi), ruxolitinib (JAK1/2i), or defactinib (FAKi), suggesting that concomitant SRC/FAK/JAK2 inhibition is potentially necessary. Importantly, the combination of repotrectinib and trametinib demonstrated increased in vivo anti-tumor effect compared to trametinib alone. Our data suggest that the combination of repotrectinib with trametinib may sustainably suppress the mutant KRAS network signaling to achieve more potent and durable anti-tumor efficacy, and that further clinical investigation of the combination treatment of a MEK inhibitor with repotrectinib in patients with KRAS mutant cancers is warranted."

Preclinical • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Sarcoma • Solid Tumor • Thoracic Cancer • ALK • EGFR • JAK1 • KRAS • ROS1

JANEX-1 improves acute pulmonary embolism through VEGF and FAK in pulmonary artery smooth muscle cells. (PubMed, Exp Biol Med (Maywood)) - "Moreover, JANEX-1 inhibited the thrombus-induced intimal hyperplasia and the expression of VEGF and FAK activation in neointimal SMCs of APE mice. The data are helpful to elucidate the pharmacological mechanism and potential therapeutic effect of JANEX-1 in APE."

Journal • Cardiovascular • Pulmonary Embolism • Thrombosis • JAK3 • VEGFA

[VIRTUAL] Repotrectinib increases effectiveness of KRAS-G12C inhibitors in KRAS-G12C mutant cancer models via simultaneous SRC/FAK/JAK2 inhibition (AACR-II 2020) - "Therapeutic targeting of KRAS has proven challenging until recent success of KRAS-G12C inhibitor AMG510 that demonstrated tumor regression in lung and colon cancer patients with a KRAS-G12C mutation. Additional combination data in KRAS-G12C mutant cancer models will be presented. Overall, these studies warrant further clinical investigation on the combination of KRAS-G12C inhibitors with repotrectinib in patients with KRAS-G12C mutation for potential response and duration improvement of current investigational KRAS-G12C inhibitors."

Preclinical • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • ALK • CASP3 • KRAS • ROS1

Upregulation of PLOD2 promotes invasion and metastasis of osteosarcoma cells (PubMed, Zhonghua Zhong Liu Za Zhi) - " Up-regulation of PLOD2 in osteosarcoma is correlated with lymphatic and distant metastasis. PLOD2 promotes invasion and metastasis of osteosarcoma might through FAK/JAK2-STAT3 signal pathway."

Journal

Co-treatment of trametinib MEK inhibitor with TPX-0005 Src/FAK/JAK2 inhibitor synergistic in KRAS mutant NSCLC cell lines and CDCP1 acts as a biomarker in KRAS mutant patients p (ELCC 2018) - "However, we have previously shown that selumetinib (MEK inhibitor) in KRAS mutant NSCLC cells caused a rebound of ERK, AKT and STAT3, as well as YAP phosphorylation (Y357), NOTCH3 and activation of RTKs, AXL and MET. The combination of trametinib plus TPX-0005 shows significant in-vitro activity in the majority of KRAS mutant NSCLC cell lines and the mRNA levels of CDCP1 could be a biomarker in KRAS mutant NSCLC p, indicating the activation of Src-YAP signaling. Clinical trials with the combination of MEK inhibitors with TPX-0005 are warranted."

Co-treatment of trametinib MEK inhibitor with TPX-0005 Src/FAK/JAK2 inhibitor synergistic in KRAS mutant NSCLC cell lines and CDCP1 acts as a biomarker in KRAS mutant patients p (ELCC 2018) - "However, we have previously shown that selumetinib (MEK inhibitor) in KRAS mutant NSCLC cells caused a rebound of ERK, AKT and STAT3, as well as YAP phosphorylation (Y357), NOTCH3 and activation of RTKs, AXL and MET. The combination of trametinib plus TPX-0005 shows significant in-vitro activity in the majority of KRAS mutant NSCLC cell lines and the mRNA levels of CDCP1 could be a biomarker in KRAS mutant NSCLC p, indicating the activation of Src-YAP signaling. Clinical trials with the combination of MEK inhibitors with TPX-0005 are warranted."