Empesertib (previously known as BAY-1161909) was developed as a selective inhibitor of the serine/threonine monopolar spindle 1 (Mps1) kinase for the treatment of cancer. Empesertib participated in phase I clinical trials in combination with paclitaxel in subjects with advanced malignancies. The studies were terminated because another more successful Mps1 inhibitor was being developed in parallel.

LIK-066 (licogliflozin) is an inhibitor of the sodium-dependent glucose co-transporter (sodium-glucose transporter; sodium-glucose transport protein; sodium-glucose linked transporter; SGLT) family members 1 and 2 (SGLT1/2) with antihyperglycemic activity. By binding to and blocking SGLT1/2, licogliflozin suppresses the reabsorption of glucose in the proximal tubule within the kidneys and enhances urinary excretion of glucose. This normalizes blood glucose levels. LIK-066 is in phase II clinical trials by Novartis for the treatment of type 2 diabetes. Licogliflozin treatment (1-84 days) leads to significant weight loss and favorable changes in a variety of metabolic parameters and incretin hormones. Dual inhibition of SGLT1/2 with licogliflozin in the gut and kidneys is an attractive strategy for treating obesity and diabetes.

PF-06747775 is an irreversible pyrrolopyrimidine inhibitor of epidermal growth factor receptor (EGFR) T790M mutants which provides potent EGFR activity against the four common mutants (exon 19 deletion (Del), L858R, and double mutants T790M/L858R and T790M/Del), selectivity over wild-type EGFR, and desirable ADME properties. The third-generation class of EGFR tyrosine kinase inhibitors PF-06747775 is a clinical candidate drug for treatment of non-small-cell lung cancer (NSCLC) driven by mutant EGFR.

Motesanib (AMG 706), a novel nicotinamide, was identified as a potent, orally bioavailable inhibitor of the VEGFR1/Flt1, VEGFR2/kinase domain receptor/Flk-1, VEGFR3/Flt4 and Kit receptors. Motesanib was expected to reduce vascular permeability and blood flow in human tumours. A phase III trial of motesanib in combination with paclitaxel and carboplatin in non-squamous NSCLC has been terminated by Takeda and subsequently the development was discontinued. Motesanib has also been investigated up to phase II in breast, thyroid, colorectal and gastrointestinal stromal tumours. However, development has been discontinued in these indications.

Bryostatin 1 is a macrocyclic lactone which can be isolated from the marine bryozoan, Bugula neritina. The effects of bryostatin 1 are attributed to its ability to selectively modulate the activity of two of the three subgroups of protein kinase C (PKC) isozymes. PKC isozymes are divided into three subgroups which differ in their molecular structures and co-factor requirements: classical PKC (cPKC), novel PKC (nPKC), and atypical PKC (aPKC). Bryostatin-1 modulates nPKC activity independent of a Ca2+ signaling. It activates cPKC only when associated with Ca2+ signaling. And, aPKC activity is not sensitive to bryostatin-1 administration. Ca2+ signals play an important role in synaptic transmission and information processing which creates a biological environment where Bryostatin-1 possesses a unique action profile. Bryostatin-1 will not affect cPKC activity in neurons which are not functioning as an active part of the signaling processing circuit with significant Ca2+influx and intracellular Ca2+ release. Bryostatin 1 is in phase II clinical trials for investigation as an anticancer agent; specifically for treatment of metastatic or recurrent head and neck cancer, ovarian epithelial cancer that has not responded to previous chemotherapy, and myelodysplastic syndrome. Bryostatin 1 has also generated interest as an investigational compound for the treatment of Alzheimer's disease.

Savolitinib (AZD6094, HMPL-504) has been demonstrated to inhibit the growth of tumors in a series of preclinical disease models, selectively for those tumors with aberrant c-Met signaling. Phase I dose escalation studies were initiated in Australia and China in 2012 and 2013 respectively. Savolitinib has demonstrated good safety and tolerability and favorable pharmacokinetic properties in late stage cancer patients, and has shown encouraging anti-tumor activity in several tumor-types, in particular for metastatic Papillary Renal Cell Cancer (PRCC). Phase II, study designed to evaluate the efficacy and safety of savolitinib in patients with locally advanced or metastatic PRCC. Approximately 20 centers in the United States, Canada, and Europe will participate in the study. The primary objective of this study is to assess the anti-tumor activity in patients with PRCC as measured by overall response rate according to Response Evaluation Criteria in Solid Tumours (“RECIST”). The secondary objectives for this study are to: assess the progression free survival and duration of response in patients with PRCC according to RECIST; assess the safety and tolerability in the treatment of patients with PRCC; characterize the pharmacokinetics and pharmacodynamics of savolitinib and metabolites following administration to steady state after multiple dosing when given orally.

Rosiptor (AQX-1125) is a once daily, orally administered small molecule being developed by Aquinox Pharmaceuticals for the treatment of asthma, bladder pain syndrome/interstitial cystitis (IC/BPS) and chronic prostatitis/chronic pelvic pain syndrome. AQX-1125 is the only clinical-stage, orally administered, SHIP1 activator. AQX-1125 significantly reduces the late response to allergen challenge, with a trend to reduce airway inflammation. AQX-1125 was safe and well tolerated and merits further investigation in inflammatory disorders. AQX-1125 has been used in trials studying the treatment of COPD, atopic dermatitis, interstitial cystitis, and bladder pain syndrome. However, the development has been discontinued.

TAK-733 had been developed by Millennium Pharmaceuticals (subsidiary of Takeda) for the treatment of adult patients with advanced non-hematological malignancies. In 2015, Takeda discontinued this studies. TAK-733 is an inhibitor of MEK that exhibits anticancer chemotherapeutic activity. In tumor explant models, TAK-733 induces tumor regression. In colorectal cancer cells and melanoma cells, this compound suppresses cell growth. Additionally, TAK-733 decreases tumor growth and weight in animal models of lung cancer and melanoma.