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    DRUG CLASS:

    pan-CLK inhibitor

    Related drugs:
    2d
    SM08502-Mediated β-Catenin Repression Synergizes with Olaparib to Inhibit Tumor Progression. (PubMed, Cancer Res Commun)
    Overcoming PARPi resistance will provide patients with therapeutic options. The study shows, in the context of resistant disease, the potential of targeting CDC-like kinase/dual-specificity tyrosine phosphorylation-regulated kinase alone and in combination with PARP inhibitors.
    Journal • BRCA Biomarker • PARP Biomarker • PD(L)-1 Biomarker • IO biomarker
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    PD-L1 (Programmed death ligand 1) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • PD-1 (Programmed cell death 1) • CTNNB1 (Catenin (cadherin-associated protein), beta 1)
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    PD-L1 expression
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    Lynparza (olaparib) • cirtuvivint (SM08502)
    2ms
    Discovery of Rogocekib (CTX-712): A Potent and Selective CLK Inhibitor for Cancer Treatment. (PubMed, ACS Med Chem Lett)
    Treatment with CTX-712 reduced the phosphorylation of serine- and arginine-rich proteins in a dose-dependent manner, leading to potent in vitro cell growth suppression and in vivo antitumor activity in lung cancer NCI-H1048 xenograft model. These findings highlight the promise of CTX-712 as a novel CLK inhibitor and its potential as a therapeutic for cancers, particularly those characterized by RNA splicing alterations.
    Journal
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    CDK1 (Cyclin-dependent kinase 1)
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    rogocekib (CTX-712)
    2ms
    Phase I Study of Rogocekib in Patients with Relapsed or Refractory Hematologic Malignancies. (PubMed, Blood Adv)
    This study was registered on the Japan Registry of Clinical Trials under jRCT2080224127. Currently, a Phase I/II Study of rogocekib in relapsed/refractory AML and higher risk MDS is ongoing in the United States (NCT05732103).
    P1 data • Journal
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    CDK1 (Cyclin-dependent kinase 1)
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    rogocekib (CTX-712)
    2ms
    Cirtuvivint/Olaparib in Breast Cancer Susceptibility Gene/Homologous Recombination Deficiency Platinum Resistant Ovarian Cancer (clinicaltrials.gov)
    P1, N=50, Recruiting, University of Colorado, Denver | Not yet recruiting --> Recruiting
    Enrollment open • Platinum resistant
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    BRCA (Breast cancer early onset)
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    Lynparza (olaparib) • cirtuvivint (SM08502)
    2ms
    CTX-712-CL-02: A Study of CTX-712 in Relapsed/Refractory Acute Myeloid Leukemia and Higher Risk Myelodysplastic Syndromes (clinicaltrials.gov)
    P1/2, N=225, Recruiting, Chordia Therapeutics, Inc. | N=170 --> 225 | Trial completion date: Apr 2028 --> Feb 2029 | Trial primary completion date: Apr 2026 --> Jun 2028
    Enrollment change • Trial completion date • Trial primary completion date
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    rogocekib (CTX-712)
    9ms
    Cirtuvivint/Olaparib in Breast Cancer Susceptibility Gene/homologous Recombination Deficiency Platinum Resistant Ovarian Cancer (clinicaltrials.gov)
    P1, N=50, Not yet recruiting, University of Colorado, Denver
    New P1 trial
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    BRCA (Breast cancer early onset)
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    Lynparza (olaparib) • cirtuvivint (SM08502)
    1year
    Targeting the NOTCH2/ADAM10/TCF7L2 Axis-Mediated Transcriptional Regulation of Wnt Pathway Suppresses Tumor Growth and Enhances Chemosensitivity in Colorectal Cancer. (PubMed, Adv Sci (Weinh))
    Furthermore, use of adavivint or blockage of ADAM10/NOTCH2/TCF7L2 signaling enhances the chemosensitivity of CRC cells. Overall, this study provides a promising candidate for the development of small-molecule inhibitors and reveals a potential therapeutic target for CRC.
    Journal
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    CCND1 (Cyclin D1) • NOTCH2 (Notch 2) • TCF7L2 (Transcription Factor 7 Like 2) • ADAM10 (ADAM Metallopeptidase Domain 10) • TCF7 (Transcription Factor 7)
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    lorecivivint (SM04690)
    1year
    Targeting the CLK2/SRSF9 splicing axis in prostate cancer leads to decreased ARV7 expression. (PubMed, Mol Oncol)
    Inhibition of the Cdc2-like kinase (CLK) family by the small molecules cirtuvivint or lorecivivint results in the decreased expression of ARV7. Both inhibitors show potent anti-proliferative effects in enzalutamide-treated or -naive PC models. Thus, targeting aberrant alternative splicing at the 3'UTR of ARV7 by disturbing the CLK2/SRSF9 axis might be a valuable therapeutic approach in late stage, ARSI-resistant PC.
    Journal
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    AR (Androgen receptor) • ARSI (Arylsulfatase Family Member I) • CDK1 (Cyclin-dependent kinase 1) • CLK2 (CDC Like Kinase 2) • SRSF9 (Serine And Arginine Rich Splicing Factor 9)
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    AR splice variant 7 • AR-V7 expression
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    Xtandi (enzalutamide) • lorecivivint (SM04690) • cirtuvivint (SM08502)
    over1year
    A Study Evaluating the Safety, Pharmacokinetics, and Preliminary Efficacy of Orally Administered SM08502 Combined With Hormonal Therapy or Chemotherapy in Subjects With Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=30, Terminated, Biosplice Therapeutics, Inc. | Phase classification: P1b --> P1 | Active, not recruiting --> Terminated; Study was terminated due business reasons by Sponsor.
    Phase classification • Trial termination • Metastases
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    ALK (Anaplastic lymphoma kinase) • NTRK (Neurotrophic receptor tyrosine kinase)
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    docetaxel • 5-fluorouracil • Vectibix (panitumumab) • abiraterone acetate • irinotecan • prednisone • leucovorin calcium • cirtuvivint (SM08502)
    over1year
    A Study Evaluating the Safety and Pharmacokinetics of Orally Administered SM08502 in Subjects With Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=82, Terminated, Biosplice Therapeutics, Inc. | Active, not recruiting --> Terminated; Study was terminated due business reasons by Sponsor.
    Trial termination • Metastases
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    cirtuvivint (SM08502)
    almost2years
    A Study Utilizing Patient-Reported Outcomes to Evaluate the Safety and Efficacy of Lorecivivint (SM04690) for the Treatment of Moderately to Severely Symptomatic Knee Osteoarthritis (STRIDES) (clinicaltrials.gov)
    P3, N=496, Completed, Biosplice Therapeutics, Inc. | Active, not recruiting --> Completed
    Trial completion • Patient reported outcomes
    almost2years
    A Long-Term Safety and Efficacy Study of Lorecivivint in Subjects With Osteoarthritis of the Knee (clinicaltrials.gov)
    P3, N=276, Completed, Biosplice Therapeutics, Inc. | Active, not recruiting --> Completed | Trial completion date: Sep 2024 --> Jun 2023 | Trial primary completion date: Sep 2024 --> Jun 2023
    Trial completion • Trial completion date • Trial primary completion date
    |
    lorecivivint (SM04690)