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    DRUG CLASS:

    ULK kinase inhibitor

    Related drugs:
    4ms
    A Phase 1/2 Study of Inlexisertib (DCC-3116) in Patients With RAS/MAPK Pathway Mutant Solid Tumors (clinicaltrials.gov)
    P1/2, N=144, Active, not recruiting, Deciphera Pharmaceuticals, LLC | Recruiting --> Active, not recruiting
    Enrollment closed • First-in-human
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    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • NF1 (Neurofibromin 1)
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    BRAF V600E • KRAS mutation • KRAS G12C • NRAS mutation • BRAF V600 • BRAF V600K • KRAS G12
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    Mekinist (trametinib) • Lumakras (sotorasib) • Mektovi (binimetinib) • inlexisertib (DCC-3116)
    over1year
    A Study of DCC-3116 in Combination with Anticancer Therapies in Participants with Advanced Malignancies (clinicaltrials.gov)
    P1/2, N=94, Recruiting, Deciphera Pharmaceuticals, LLC | Trial completion date: Jun 2027 --> Mar 2029
    Trial completion date
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    BRAF (B-raf proto-oncogene) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha)
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    BRAF V600E • BRAF V600 • KIT mutation • KIT exon 11 mutation • PDGFRA mutation
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    Qinlock (ripretinib) • inlexisertib (DCC-3116)
    over1year
    Inhibition of ULK1/2 and KRASG12C controls tumor growth in preclinical models of lung cancer. (PubMed, Elife)
    Mutational activation of KRAS occurs commonly in lung carcinogenesis and, with the recent U.S. Food and Drug Administration approval of covalent inhibitors of KRASG12C such as sotorasib or adagrasib, KRAS oncoproteins are important pharmacological targets in non-small cell lung cancer (NSCLC)...Moreover, the combination of DCC-3116, a selective ULK1/2 inhibitor, plus sotorasib displays cooperative/synergistic suppression of human KRASG12C-driven lung cancer cell proliferation in vitro and superior tumor control in vivo. Additionally, in genetically engineered mouse models of KRASG12C-driven NSCLC, inhibition of either KRASG12C or ULK1/2 decreases tumor burden and increases mouse survival. Consequently, these data suggest that ULK1/2-mediated autophagy is a pharmacologically actionable cytoprotective stress response to inhibition of KRASG12C in lung cancer.
    Preclinical • Journal
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    KRAS (KRAS proto-oncogene GTPase)
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    Lumakras (sotorasib) • Krazati (adagrasib) • inlexisertib (DCC-3116)
    over1year
    A Phase 1/2 Study of DCC-3116 in Patients With RAS/MAPK Pathway Mutant Solid Tumors (clinicaltrials.gov)
    P1/2, N=173, Recruiting, Deciphera Pharmaceuticals LLC | N=323 --> 173 | Trial completion date: Oct 2024 --> Aug 2028 | Trial primary completion date: Apr 2024 --> Aug 2027
    Enrollment change • Trial completion date • Trial primary completion date • Combination therapy • Metastases
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    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • NF1 (Neurofibromin 1)
    |
    Mekinist (trametinib) • Lumakras (sotorasib) • Mektovi (binimetinib) • inlexisertib (DCC-3116)
    over1year
    A Study of DCC-3116 in Combination With Anticancer Therapies in Participants With Advanced Malignancies (clinicaltrials.gov)
    P1/2, N=94, Recruiting, Deciphera Pharmaceuticals LLC | N=170 --> 94
    Enrollment change • Combination therapy • Metastases
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    BRAF (B-raf proto-oncogene) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha)
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    Qinlock (ripretinib) • inlexisertib (DCC-3116)
    2years
    Ginsenoside Rg5 enhances the radiosensitivity of lung adenocarcinoma via reducing HSP90-CDC37 interaction and promoting client protein degradation. (PubMed, J Pharm Anal)
    Ginsenoside Rg5 or MRT67307 (an IKKε/TBK1 inhibitor) pretreatment suppressed irradiation-induced elevation of the LC3-II/β ratio and restored irradiation-induced downregulation of p62 expression...In conclusion, ginsenoside Rg5 may be a potential radiosensitizer for lung adenocarcinoma. It interacts with HSP90α and reduces the binding between HSP90 and CDC37, thereby increasing the ubiquitin-mediated proteasomal degradation of the HSP90-CDC37 client proteins.
    Journal
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    CDK4 (Cyclin-dependent kinase 4) • HSP90AA1 (Heat Shock Protein 90 Alpha Family Class A Member 1Heat Shock Protein 90 Alpha Family Class A Member 1)
    over2years
    Ginsenoside Rg5's Enhancement of Radiosensitivity of Lung Adenocarcinoma via Reducing HSP90 CDC37 Interaction and Promoting Client Protein Degradation. (PubMed, Int J Radiat Oncol Biol Phys)
    ginsenoside Rg5 may be a potential radiosensitizer for lung adenocarcinoma. It interacts with HSP90 and reduces the binding between HSP90 and CDC37, thereby increasing the ubiquitin-mediated proteasomal degradation of the HSP90-CDC37 client proteins.
    Journal
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    CDK4 (Cyclin-dependent kinase 4) • RAF1 (Raf-1 Proto-Oncogene Serine/Threonine Kinase) • HSP90AA1 (Heat Shock Protein 90 Alpha Family Class A Member 1Heat Shock Protein 90 Alpha Family Class A Member 1)
    over2years
    A Study of DCC-3116 in Combination With Anticancer Therapies in Participants With Advanced Malignancies (clinicaltrials.gov)
    P1/2, N=170, Recruiting, Deciphera Pharmaceuticals LLC | Not yet recruiting --> Recruiting
    Enrollment open • Combination therapy • Metastases
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    BRAF (B-raf proto-oncogene) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha)
    |
    BRAF V600E • BRAF V600 • KIT mutation • KIT exon 11 mutation • PDGFRA mutation
    |
    Erbitux (cetuximab) • Braftovi (encorafenib) • Qinlock (ripretinib) • inlexisertib (DCC-3116)
    over2years
    A Study of DCC-3116 in Combination With Anticancer Therapies in Participants With Advanced Malignancies (clinicaltrials.gov)
    P1/2, N=170, Not yet recruiting, Deciphera Pharmaceuticals LLC
    New P1/2 trial • Combination therapy • Metastases
    |
    BRAF (B-raf proto-oncogene) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha)
    |
    BRAF V600E • BRAF V600 • KIT mutation • KIT exon 11 mutation • PDGFRA mutation
    |
    Erbitux (cetuximab) • Braftovi (encorafenib) • Qinlock (ripretinib) • inlexisertib (DCC-3116)
    almost3years
    DCC-3116, a first-in-class selective inhibitor of ULK1/2 kinases and autophagy, synergizes with encorafenib and cetuximab in BRAF V600E mutant colorectal cancer models (AACR 2023)
    These preclinical data demonstrate that BRAF inhibitors in combination with EGFR blockade such as E+C activate ULK-mediated autophagy as an ASR resistance mechanism which can be inhibited by DCC-3116, providing the rationale to study the combination of DCC-3116 with E+C in BRAF V600E mutated CRC patients. DCC-3116 is currently in a Phase 1 clinical trial in patients with advanced solid tumors.
    Preclinical
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    BRAF (B-raf proto-oncogene)
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    BRAF V600E • EGFR mutation • BRAF V600
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    Erbitux (cetuximab) • Braftovi (encorafenib) • inlexisertib (DCC-3116)