Professor Wang’s research focuses on the discovery and development of novel kinase inhibitor drugs for cancer treatment. Current ongoing research programs include:

• Cyclin-dependent Kinase (CDK) Inhibitors as Anti-Cancer Agents

The discovery of cyclin-dependent kinases (CDKs) as key regulators of the cell cycle by Hartwell, Nurse, and Hunt, which earned them the 2001 Nobel Prize in Physiology & Medicine, established CDKs as important targets in cancer therapy. Tumor-associated cell-cycle defects often arise from alterations in CDK activity. While several CDK4/6 inhibitors have been approved for the treatment of breast cancer in the clinic, progress in developing mono-specific inhibitors remains limited. Our research aims to develop inhibitors with high specificity against individual CDK family members, particularly CDK2, CDK4, CDK5, CDK6, CDK8, or CDK9. These inhibitors are being designed as highly effective, low-toxicity therapeutics for a range of cancers, including haematological malignancies (AML, ALL, CLL) and solid tumors such as brain, breast, colorectal, lung, melanoma, ovarian, pancreatic, and prostate cancer, respectively.

• Targeting Tyro3, Axl, and Mer (TAM) Kinases for Cancer Immunotherapy

TAM kinases (Tyro3, Axl, Mer) are over-expressed in many cancers and are associated with poor prognosis, drug resistance, and metastasis. Acting as immune checkpoints, similar to CTLA-4, PD-1, and PD-L1, TAM kinase inhibition can enhance tumor immunity. We have identified a class of highly potent and selective TAM kinase inhibitors that demonstrate strong anti-cancer activity across multiple cancer cell lines. In animal models, our lead candidate has shown significant anti-tumor efficacy, inducing tumor regression at a single-digit low milligram dosage by oral administration. Additionally, the compound enhances anti-tumor immune responses by increasing CD3+/CD8+ T cell populations in murine syngeneic models. This project aims to understand the mechanism of action and evaluate the therapeutic potential of these compounds as cancer immunotherapies.

• Highly Selective and Potent FLT3 Inhibitors for Hematologic Cancers

FMS-like tyrosine kinase 3 (FLT3) is highly expressed in a range of hematologic malignancies, including 70-100% of AML subtypes, as well as ALL and CML. Patients with FLT3 mutations have poor prognoses, experience higher relapse rates, and face increased mortality. We have identified a highly selective FLT3 inhibitor that exhibits picomolar potencies against FLT3 and all eight known FLT3 mutations, including FLT3 (ITD), FLT3 (D835Y), FLT3 (F594_R595insR), FLT3 (F594_R595insREY), FLT3 (ITD)-NPOS, FLT3 (ITD)-W51, FLT3 (R595_E596insEY), and FLT3 (Y591V592insVDFREYEYD). The candidate demonstrates high efficacy against tumor xenografts and induced complete remission in all in vivo AML models, leading to a 100% survival rate. Moreover, the compound is highly synergistic with venetoclax, a BCL-2 inhibitor, and has the potential to overcome venetoclax resistance. We seek partnership to advance this program toward clinical trials.

Professor Wang’s research is committed to advancing targeted cancer therapies, improving patient outcomes through the pre-clinical and clinical development of innovative kinase inhibitors.