Adavosertib's clinical promise was challenged by inter-individual variations in response and side effects. Because of these promising preclinical outcomes, other WEE1 kinase inhibitors (Azenosertib, SC0191, IMP7068, PD0407824, PD0166285, WEE1-IN-5, Zedoresertib, WEE1-IN-8, and ATRN-1051) are being developed, with several currently being evaluated in clinical trials or as an adjuvant to chemotherapies...Reliable predictors of clinical responses based on mechanistic insights remain an important unmet need. Herein, we review the role of WEE1 inhibition therapy in breast cancer.

5 months ago

Review • Journal

STING (stimulator of interferon response cGAMP interactor 1) • CDK2 (Cyclin-dependent kinase 2) • CDC25C (Cell Division Cycle 25C) • CDK1 (Cyclin-dependent kinase 1) • PKMYT1 (Protein Kinase Membrane Associated Tyrosine/Threonine 1) • GNRP (Ras-Specific Guanine Nucleotide-Releasing Factor 1)

adavosertib (AZD1775) • azenosertib (ZN-c3) • SC0191 • APR-1051 • IMP7068

over5years

[VIRTUAL] Preclinical evaluation of SC0191, a small molecule inhibitor of Wee1 kinase. (ASCO 2020)

Moreover, SC0191 oral administration showed significant antitumor efficacy which was better than AZD1775, in the NCI-H446 and BxPC-3 CDX mouse models, respectively. A novel Wee1 inhibitor, SC0191, has demonstrated excellent antitumor efficacy in TP53 mutant solid cancer preclinical studies, and represents a promising clinical candidate for treating solid tumors, such as SCLC and PC. Research Funding: Sagacity

over 5 years ago

Preclinical

TP53 (Tumor protein P53) • CDK1 (Cyclin-dependent kinase 1)

TP53 mutation

adavosertib (AZD1775) • SC0191