KPT-9274

12/01/2019 - "In addition, KPT-9274 improved overall survival in vivo in 2 different mouse models of AML and reduced tumor development in a patient-derived xenograft model of AML. "
01/01/2020 - "Furthermore, combination of anti-PD-1 with the PAK4 inhibitor KPT-9274 improved anti-tumor response compared with anti-PD-1 alone. "
01/01/2023 - "We show that NAMPT inhibitor KPT-9274 and Fulv works synergistically to reduce metastatic tumor burden. "
05/28/2020 - "Male BALB/cJ mice were injected subcutaneously with RENCA cells and, after tumors were palpable, they were treated with KPT-9274 and/or anti-programmed cell death 1 (PDCD1; PD1) antibody for 21 days. "
01/01/2016 - "When KPT-9274 was administered in vivo to a 786-O (VHL-mut) human RCC xenograft model, there was dose-dependent inhibition of tumor growth with no apparent toxicity; KPT-9274 demonstrated the expected on-target effects in this mouse model. "

11/29/2019 - "KPT-9274 given orally at 150 mg/kg 5 days/week for 4 weeks dramatically reduced PNET sub-cutaneous tumor growth. "
10/01/2021 - "KPT-9274, given at 150 mg/kg in combination with sub-MTD everolimus (2.5 mg/kg), significantly suppressed two PNET-derived xenografts. "
11/29/2019 - "KPT-9274 suppressed NAD pool and ATP levels in PNET cell lines. "
11/29/2019 - "Treatment with KPT-9274 (currently in a Phase I trial or analogs, PF3758309 (the PAK4 selective inhibitor) or FK866 (the NAMPT inhibitor)) suppressed the growth of PNET cell lines and synergized with the mammalian target of rapamycin (mTOR) inhibitors everolimus and INK-128. "
10/01/2021 - "Molecular analysis showed alteration of mTORC2 through downregulation of RICTOR as a mechanism supporting synergy with everolimus in vitro KPT-9274 suppressed β-catenin activity via inhibition of PAK4, highlighting the cross-talk between Rho GTPases and Wnt signaling in PNETs. "

01/01/2016 - "Dual and Specific Inhibition of NAMPT and PAK4 By KPT-9274 Decreases Kidney Cancer Growth."
05/28/2020 - "Although we have previously shown efficacy of the dual PAK4/nicotinamide phosphoribosyltransferase (NAMPT) inhibitor KPT-9274, and the immune checkpoint inhibitors (CPI) have shown utility in the clinic, there has been no evaluation of this combination either clinically or in an immunocompetent animal model of kidney cancer. "

01/01/2021 - "In vivo studies using PAK4 inhibitors, KPT-9274 and PF-3758309 demonstrated significant inhibition of primary and metastatic tumor formation, while transcriptomic analysis of PAK4-inhibitor-treated tumors identified concomitant suppression of Notch, β-catenin, and hypoxia-mediated signatures. "

01/01/2017 - "Our results indicate that KPT-9274 is a novel therapeutic option for triple negative breast cancer therapy."
01/01/2017 - "A novel orally bioavailable compound KPT-9274 inhibits PAK4, and blocks triple negative breast cancer tumor growth."
01/01/2020 - "KPT-9274, an Inhibitor of PAK4 and NAMPT, Leads to Downregulation of mTORC2 in Triple Negative Breast Cancer Cells."
01/01/2017 - "We find that KPT-9274 (and its analog, KPT-8752) can reduce the steady state level of PAK4 protein in triple negative breast cancer cells. "
01/01/2017 - "Most importantly, oral administration of KPT-9274 reduces tumorigenesis in mouse models of human triple negative breast cancer. "