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Aurora A Inhibitor

JAB-2485 is an Aurora Kinase A (AURKA) inhibitor developed independently by Jacobio Pharma. It inhibits AURKA effectively and does not affect the activity of other kinases structurally similar to AURKA, minimizing the toxicity of the drug and improving the therapeutic window.

At present, there is no commercialized Aurora A inhibitor globally. As one of the few highly selective AURKA inhibitors in the world, JAB-2485 may greatly improve the survival of patients with RB loss small cell lung cancer and patients with high expression of AURKA.

Preclinical studies have shown that JAB-2485 alone or in combination with chemotherapy (e.g., cisplatin and paclitaxol) have demonstrated potent antitumor effects in human neuroblastoma (NB), small cell lung cancer (SCLC), and triple-negative breast cancer (TNBC). In addition, JAB-2485 has shown a favorable pharmacokinetic profile. Applying JAB-2485 either alone or in combination is a potential therapeutic option for cancer patients.

Mechanism of Action

JAB-2485 is a highly selective small molecule Aurora Kinase A (AURKA) inhibitor. AURKA plays an important role in cellular division, is involved in centrosome maturation and chromosomal segregation. JAB-2485 significantly inhibits AURKA activity at the cellular level, leading to cell cycle arrest in the G2/M phase, resulting in abnormal mitosis and inducing apoptosis, and ultimately inhibiting the growth of tumor cells.

RB loss is common in small cell lung cancer. RB is an important tumor suppressor gene. RB loss results in the continued activation of the spindle assembly checkpoint (SAC), thus allowing tumor cells to undergo normal mitosis and proliferation, leading to tumor growth. Recent studies have shown that tumors with RB loss are highly sensitive to AURKA inhibitors. Targeted AURKA can effectively interfere with mitosis and kill tumors in RB-loss tumors through synthetic lethality.

Indications

CD73 is over-expressed in many malignant tumors, including melanoma, triple negative breal efficacy in non-small cell lung cancer, triple negative breast cancer, renal cell carcinoma and other solid tumors.

The incidence of these cancers is significant, disease progression is rapid, and current clinical treatments are impacted by a lack of drug development or high drug resistance after chemotherapy. JAB-2485 has potential to bring more treatment options to patients.

Clinical Trial
Asset Programs Region Phase Indication Registration information
JAB-2485 Mono Therapy U.S. I/IIa Advanced Solid Tumors NA
Reference
  1. Cancer Discov. 2019 Feb;9(2):248-263. doi: 10.1158/2159-8290.CD-18-0469. Epub 2018 Oct 29.
  2. Cancer Discov. 2019 Feb;9(2):248-263. doi: 10.1158/2159-8290.CD-18-0469. Epub 2018 Oct 29.
  3. Cancer Discov. 2019 Feb;9(2):248-263. doi: 10.1158/2159-8290.CD-18-0469. Epub 2018 Oct 29.
  4. Cell Death Dis. 2019 Nov 21;10(12):881. doi: 10.1038/s41419-019-2120-1.