PCI-27483 is a reversible small-molecule inhibitor of activated factor VII (factor VIIa) with potential antineoplastic and antithrombotic activities. FVII, a serine protease, becomes activated (FVIIa) upon binding with TF forming the FVIIa/TF complex, which induces intracellular signaling pathways by activating protease activated receptor 2 (PAR-2). Upon subcutaneous administration, factor VIIa inhibitor PCI-27483 selectively inhibits factor FVIIa in the VIIa/TF complex, which may prevent PAR-2 activation and PAR2-mediated signal transduction pathways, thereby inhibiting tumor cell proliferation, angiogenesis, and metastasis of TF-overexpressing tumor cells. A phase I study in healthy volunteers was conducted to assess the PD and PK profiles of PCI- 27483 following a single, SC injection. The halflife of PCI-27483 was 10-12 h. The International Normalized Ratio (INR) was strongly correlated with drug plasma concentration. PCI-27483 was well tolerated. This compound has being evaluated in a phase Ib/II trial in patients with pancreatic cancer receiving treatment with gemcitabine. However, no recent development has been reported. The compound was originally developed by Celera, then licensed to Pharmacyclics (acquired by Abbvie in 2015) later. In 2012, the product was licensed to Novo Nordisk by Pharmacyclics for disease outside of oncology.

DBPR-108 is a potent, selective, and orally bioavailable dipeptide-derived inhibitor of DPP4 with IC50 of 15 nM; no inhibition on DDP8 and DPP9, which is in phase I clinical trial as a potential treatment of type 2 diabetes.

Napabucasin (BBI608) is an orally administered small molecule that blocks stem cell activity in cancer cells by targeting the signal transducer and activator of transcription 3 pathway, which is over-activated in many types of cancer and has been shown to be an important pathway in cancer stem cell-mediated propagation of cancer. Napabucasin has already shown promising efficacy on different cancer types, both as a monotherapy and in combination with conventional chemotherapeutic agents. Early-phase trials have shown promising anti-tumor efficacy when patients are treated with napabucasin in combination with standard chemotherapy agents, and preclinical results suggest that napabucasin can synergize with chemotherapy agents, such as paclitaxel, to potentially overcome drug resistance. Encouraging phase Ib/II trial results warrant further clinical study with napabucasin and paclitaxel combination therapy, especially in malignancies where there is an urgent and unmet need for effective therapeutics, such as in patients with advanced pancreatic adenocarcinoma.

Granotapide (JTT-130) has been studied for use in treatment of diabetes mellitus type II. This intestine-specific microsomal transfer protein inhibitor has hypoglycemic effects. Granotapide is thought to block fat absorption, which results in enhanced glucose-stimulated insulin secretion and enhanced insulin sensitivity. In an animal study, granotapide improved hyperglycemia and dyslipidemia via a mechanism independent of suppression of food intake. Granotapide enhances glucagon-like peptide-1 secretion and reduces lipotoxicity. A phase 2 study has been conducted to evaluate the effect of JTT-130 on diabetes as well as the safety and tolerability of JTT-130 in obese Type 2 diabetic patients.