TNIK inhibition is more effective in c-MYChigh SCLC, acting through downregulation of c-MYC levels. It also decreases the production of CCL2, supporting the rationale for combination therapy with immune checkpoint inhibitors in c-MYChigh SCLC.

P2, N=40, Recruiting, InSilico Medicine Hong Kong Limited | N=60 --> 40

Despite over 10 patents disclosing multiple scaffolds since 2008, only one inhibitor, INS018_055, has advanced to clinical trials to treat idiopathic pulmonary fibrosis. For the oncology indications, this is largely due to complexities in the relationship between TNIK and oncogenic pathways. Additionally, key characteristics of the molecules, such as kinase selectivity, physicochemical properties and pharmacokinetic profiles, have played significant roles in determining whether the molecules are drug-like enough to advance to clinical trials.

This paper aims to comprehensively review the latest progress in the structural characteristics and pharmacological effects of small-molecule TNIK inhibitors. By doing so, it seeks to offer valuable insights and guidance for the future development of more effective TNIK inhibitors.

This identified TNIK, which is modulated by NCB-0846, as a novel target for platinum-resistant HGSC...Our findings identified the TNIK-CDK9 axis as druggable targets mediating platinum resistance and cell viability in HGSC. With AI at the forefront of drug discovery, this work highlights how to ensure that AI findings are biologically relevant by combining compound screens with physiologically relevant models thus supporting the identification and validation of potential drug targets.

P2, N=71, Completed, InSilico Medicine Hong Kong Limited | Active, not recruiting --> Completed

P2, N=70, Active, not recruiting, InSilico Medicine Hong Kong Limited | Recruiting --> Active, not recruiting

The combination of NCB-0846 with cisplatin or etoposide was at best additive. In a subcutaneous xenograft in vivo model, pretreatment with NCB-0846 significantly enhanced the efficacy of IR and caused elevated necrosis in TNIKhigh LK2 tumors but not TNIKlow KNS62 tumors. Overall, these results indicate that TNIK inhibition may be a promising strategy to increase the efficacy of radiotherapy in patients with LSCC with high TNIK expression.

In summary, we proposed a novel regulatory mechanism in which TNIK-mediated cytoskeleton remodeling and cell migration to regulate tumor progression in PTC. TNIK is a therapeutic target in PTC and NCB-0846 would act as a novel targeted drug for PTC therapy.

The combination of NCB-0846 with cisplatin or etoposide was at best additive. In a subcutaneous xenograft in vivo model, pretreatment with NCB-0846 significantly enhanced the efficacy of IR and caused elevated necrosis in TNIKhigh LK2 tumors but not TNIKlow KNS62 tumors. Overall, these results indicate that TNIK inhibition may be a promising strategy to increase the efficacy of radiotherapy in LSCC patients with high TNIK expression.