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  • ||||||||||  Review, Journal, BRCA Biomarker, PARP Biomarker:  USP1 inhibition: A journey from target discovery to clinical translation. (Pubmed Central) -  May 25, 2025   
    Other USP1 inhibitors, including SIM0501, XL309-101, and HSK39775, are currently in early clinical development. In this review, we provide an overview of the molecular function of USP1 and its importance as a therapeutic target in oncology, before focusing on the current state of preclinical and clinical development of USP1 inhibitors.
  • ||||||||||  INS018_055 / Insilico Medicine
    Journal:  AI-Driven Robotics Laboratory Identifies Pharmacological TNIK Inhibition as a Potent Senomorphic Agent. (Pubmed Central) -  Feb 18, 2025   
    These findings reveal TNIK's previously unappreciated role in cellular senescence and INS018_055's senomorphic potential in mitigating processes well-established as driving organismal aging. Thus, TNIK inhibition as a novel senomorphic strategy may inform future therapeutic approaches for diverse aging-related diseases.
  • ||||||||||  INS018_055 / Insilico Medicine
    Clinical, Preclinical, Journal:  A small-molecule TNIK inhibitor targets fibrosis in preclinical and clinical models. (Pubmed Central) -  Jan 17, 2025   
    P1
    Using AI-driven methodology, we generated INS018_055, a small-molecule TNIK inhibitor, which exhibits desirable drug-like properties and anti-fibrotic activity across different organs in vivo through oral, inhaled or topical administration...A separate phase I trial in China, CTR20221542, also demonstrated comparable safety and pharmacokinetic profiles. This work was completed in roughly 18 months from target discovery to preclinical candidate nomination and demonstrates the capabilities of our generative AI-driven drug-discovery pipeline.
  • ||||||||||  ISM3412 / Insilico Medicine
    Enrollment open:  Study of ISM3412 in Participants With Locally Advanced/Metastatic Solid Tumors (clinicaltrials.gov) -  Jan 5, 2025   
    P1,  N=80, Recruiting, 
    This work was completed in roughly 18 months from target discovery to preclinical candidate nomination and demonstrates the capabilities of our generative AI-driven drug-discovery pipeline. Not yet recruiting --> Recruiting
  • ||||||||||  ISM5411 / Insilico Medicine
    Trial completion:  Study Evaluating ISM5411 Administered Orally to Healthy Volunteers (clinicaltrials.gov) -  Nov 7, 2024   
    P1,  N=79, Completed, 
    Currently, phase II clinical trials of compound 4 are underway for the treatment of idiopathic pulmonary fibrosis (IPF). Recruiting --> Completed
  • ||||||||||  ISM3412 / Insilico Medicine
    Journal:  Discovery of novel MAT2A inhibitors by an allosteric site-compatible fragment growing approach. (Pubmed Central) -  Feb 19, 2024   
    X-ray co-crystal structure revealed that compound 7 fully occupies the allosteric pocket of MAT2A as a single molecule mimicking MAT2B. By introducing additional backbone interactions and rigidifying the requisite linker extensions, we generated compound 8, which exhibited single digit nanomolar enzymatic and sub-micromolar cellular inhibitory potency for MAT2A.
  • ||||||||||  rentosertib (INS018_055) / Insilico Medicine
    Phase classification:  Study Evaluating INS018_055 Administered Orally to Subjects with Idiopathic Pulmonary Fibrosis (IPF) (clinicaltrials.gov) -  Dec 26, 2023   
    P2,  N=60, Recruiting, 
    By introducing additional backbone interactions and rigidifying the requisite linker extensions, we generated compound 8, which exhibited single digit nanomolar enzymatic and sub-micromolar cellular inhibitory potency for MAT2A. Phase classification: P2a --> P2
  • ||||||||||  ISM5411 / Insilico Medicine
    Enrollment open:  Study Evaluating ISM5411 Administered Orally to Healthy Volunteers (clinicaltrials.gov) -  Nov 13, 2023   
    P1,  N=76, Recruiting, 
    Not yet recruiting --> Recruiting | Phase classification: P2a --> P2 Not yet recruiting --> Recruiting
  • ||||||||||  Undisclosed CDK8 inhibitor / Insilico Medicine
    Journal:  Discovery of Potent, Selective, and Orally Bioavailable Small-Molecule Inhibitors of CDK8 for the Treatment of Cancer. (Pubmed Central) -  May 3, 2023   
    Here, we report the successful optimization of an azaindole series of CDK8 inhibitors that were identified and further progressed through a structure-based generative chemistry approach. In several optimization cycles, we improved in vitro microsomal stability, kinase selectivity, and in vivo pharmacokinetic profile cross-species, leading to the discovery of compound 23, which demonstrated robust tumor growth inhibition in multiple in vivo efficacy models after oral administration.
  • ||||||||||  ISM6466A / Insilico Medicine
    Discovery and evaluation of ISM6466A, a novel covalent CDK12 inhibitor for the treatment of cancer (Section 17; Poster Board #2) -  Mar 14, 2023 - Abstract #AACR2023AACR_7165;    
    Results from a 28-day rat DRF study revealed that the compound did not show evident signs of toxicity at the tested doses, suggesting a reasonable safety window for ISM6466A.In summary, the novel, covalent, small-molecule CDK12 inhibitor, ISM6466A, demonstrated excellent preclinical efficacy along with favorable drug-like properties. Our results underscore the therapeutic potential of ISM6466A for the treatment of cancer.
  • ||||||||||  ISM3412 / Insilico Medicine
    ISM3412, a novel and selective MAT2A inhibitor for the treatment of cancer (Section 18; Poster Board #3) -  Mar 14, 2023 - Abstract #AACR2023AACR_2561;    
    Further, it was well tolerated with no significant hepatobiliary toxicity. In conclusion, ISM3412 is a novel and highly selective MAT2A inhibitor for MTAP-deficient cancers, and merits clinical evaluation.
  • ||||||||||  ISM3091 / Insilico Medicine
    ISM3091, a novel selective USP1 inhibitor as a targeted anticancer therapy (Section 18; Poster Board #2) -  Mar 14, 2023 - Abstract #AACR2023AACR_2560;    
    ISM3091also displayed very favorable ADME propertiesand PK profiles, and GLP toxicology studies indicated that it was well tolerated without significant gastrointestinal toxicity or hematological toxicity. These data support the future clinical development of ISM3091 as a potential best-in-class USP1 inhibitor not only for PARPi-resistant/responsive HRD-mutant cancers, both, as a single agent as well as in combination with PARPi, but also for subsets of HR-proficient cancers.
  • ||||||||||  rentosertib (INS018_055) / Insilico Medicine
    Enrollment open:  A Phase 1, Evaluate the Safety, Tolerability, and Pharmacokinetics of INS018_055 in Healthy Subjects (clinicaltrials.gov) -  Mar 13, 2022   
    P1,  N=80, Recruiting, 
    These data support the future clinical development of ISM3091 as a potential best-in-class USP1 inhibitor not only for PARPi-resistant/responsive HRD-mutant cancers, both, as a single agent as well as in combination with PARPi, but also for subsets of HR-proficient cancers. Not yet recruiting --> Recruiting