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    DRUG CLASS:

    RPS6 inhibitor

    Related drugs:
    9ms
    A Study of TAS0612 in Participants With Advanced or Metastatic Solid Tumor Cancer (clinicaltrials.gov)
    P1, N=47, Terminated, Taiho Oncology, Inc. | N=100 --> 47 | Trial completion date: Jul 2027 --> Nov 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Apr 2025 --> Nov 2024; Taiho Oncology as the sponsor of study TAS0612-101, has made a strategic decision to terminate the TAS0612-101 study, taking into consideration the safety profile of TAS0612 and the absence of encouraging anti-tumor activity.
    Enrollment change • Trial completion date • Trial termination • Trial primary completion date
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    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • PTEN (Phosphatase and tensin homolog) • NF1 (Neurofibromin 1)
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    KRAS mutation • HR positive • KRAS G12C • HER-2 negative • KRAS G12D • KRAS G12 • HR positive + HER-2 negative
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    TAS0612
    1year
    A Study of TAS0612 in Participants With Advanced or Metastatic Solid Tumor Cancer (clinicaltrials.gov)
    P1, N=100, Active, not recruiting, Taiho Oncology, Inc. | Recruiting --> Active, not recruiting | Trial primary completion date: Aug 2024 --> Apr 2025
    Enrollment closed • Trial primary completion date • Metastases
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    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • PTEN (Phosphatase and tensin homolog) • NF1 (Neurofibromin 1)
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    KRAS mutation • HR positive • KRAS G12C • HER-2 negative • KRAS G12D • NF1 mutation • KRAS G12 • HR positive + HER-2 negative
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    TAS0612
    1year
    Higher risk of recurrence in early-stage breast cancer patients with increased levels of ribosomal protein S6. (PubMed, Sci Rep)
    When assessed in combination with lymph node status, the predictive capacity was higher compared to both univariate models individually. In conclusion, pS6 could represent a novel independent marker for predicting recurrence risk in luminal breast cancer.
    Observational data • Retrospective data • Journal
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    HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • RPS6 (Ribosomal Protein S6)
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    HER-2 positive • HR positive • HER-2 negative • PIK3CA mutation • AKT1 mutation • HR positive + HER-2 negative • PTEN mutation + HR positive • HER-2 negative + HR positive + AKT1 mutation
    1year
    Robust anti-myeloma effect of TAS0612, an RSK/AKT/S6K inhibitor, with venetoclax regardless of cytogenetic abnormalities. (PubMed, Leukemia)
    Moreover, the combination of TAS0612 with venetoclax (VEN) showed the synergy in inducing apoptosis in HMCLs irrespective of the t(11;14) translocation status. TAS0612 alone and combined with VEN are new potent candidate therapeutic strategies for MM, regardless of cytogenetic/genetic profiles, facilitating its future clinical development.
    Journal
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    RPS6KA3 (Ribosomal Protein S6 Kinase A3) • PDPK1 (3-Phosphoinositide dependent protein kinase 1)
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    Chr t(11;14)
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    Venclexta (venetoclax) • TAS0612
    over1year
    Computer-assisted discovery and evaluation of potential ribosomal protein S6 kinase beta 2 inhibitors. (PubMed, Comput Biol Med)
    Among the compounds, compound 1 induced restrictive dissociation of S6K2 in the presence of a flexible region, compound 8 achieved strong stability through hydrogen bonding with Lys99, compound 9 caused S6K2 tightening, and the binding of compound 16 was heavily influenced by hydrophobic interactions. This study suggests that these four potential inhibitors with different mechanisms of action could provide potential therapeutic options.
    Journal
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    RPS6 (Ribosomal Protein S6)
    almost2years
    A Study of TAS0612 in Participants With Advanced or Metastatic Solid Tumor Cancer (clinicaltrials.gov)
    P1, N=100, Recruiting, Taiho Oncology, Inc. | N=242 --> 100 | Trial completion date: Jun 2024 --> Jul 2027 | Trial primary completion date: Oct 2023 --> Jul 2024
    Enrollment change • Trial completion date • Trial primary completion date • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • PTEN (Phosphatase and tensin homolog) • NF1 (Neurofibromin 1)
    |
    KRAS mutation • HR positive • KRAS G12C • HER-2 negative • KRAS G12D • NF1 mutation • KRAS G12 • HR positive + HER-2 negative
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    TAS0612
    almost2years
    Ribosomal protein S6 kinase 2 (RPS6KB2) is a potential immunotherapeutic target for cancer that upregulates proinflammatory cytokines. (PubMed, Mol Biol Rep)
    Our research indicates that RPS6KB2 is a prognostic biomarker associated with immune infiltration in cancer that can affect antitumor immunity by increasing secretion of proinflammatory factors, providing a potential drug target for cancer treatment.
    Journal • IO biomarker
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    MSI (Microsatellite instability) • BCL2 (B-cell CLL/lymphoma 2) • MMP2 (Matrix metallopeptidase 2) • BAX (BCL2-associated X protein) • MMP9 (Matrix metallopeptidase 9) • PCNA (Proliferating cell nuclear antigen) • RPS6 (Ribosomal Protein S6) • RPS6KB2 (Ribosomal Protein S6 Kinase B2)
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    BCL2 expression • BAX expression • PCNA expression
    2years
    TAS0612, a novel RSK, AKT, and S6K inhibitor, exhibits antitumor effects in preclinical tumor models. (PubMed, Mol Cancer Ther)
    Additionally, TAS0612 demonstrated the persistence of blockade of downstream growth and anti-apoptotic signals, despite activation of upstream effectors in the signaling pathway and FoxO-dependent re-expression of HER3. In conclusion, TAS0612 with RSK/AKT/S6K inhibitory activity may provide a novel therapeutic strategy for cancer patients to improve clinical responses and overcome resistance mechanisms.
    Preclinical • Journal
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    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • PTEN (Phosphatase and tensin homolog) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3)
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    KRAS mutation • BRAF mutation • ERBB3 expression
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    TAS0612
    2years
    Triple targeting of RSK, AKT, and S6K as pivotal downstream effectors of PDPK1 by TAS0612 in B-cell lymphomas. (PubMed, Cancer Sci)
    At the molecular level, TAS0612 caused significant downregulation of MYC and mTOR target genes while inducing the tumor suppressor TP53INP1 protein in these cell lines. These results prove that the simultaneous blockade of RSK2, AKT, and S6K, which are the pivotal downstream substrates of PDPK1, is a novel therapeutic target for the various disease subtypes of BCLs and line up TAS0612 as an attractive candidate agent for BCLs for future clinical development.
    Journal
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    MYC (V-myc avian myelocytomatosis viral oncogene homolog) • PLK1 (Polo Like Kinase 1) • RPS6KA3 (Ribosomal Protein S6 Kinase A3) • PDPK1 (3-Phosphoinositide dependent protein kinase 1) • TP53INP1 (Tumor Protein P53 Inducible Nuclear Protein 1)
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    TAS0612