E-6005 is a novel PDE4 inhibitor developed as a topical agent for atopic dermatitis (AD). It potently and selectively inhibited human PDE4 activity and suppressed the production of various cytokines from human lymphocytes and monocytes. In mice models, the topical application of E6005 produced an immediate antipruritic effect as well as an anti-inflammatory effect with reduced expression of cytokines/adhesion molecules. E-6005 increases the cutaneous concentration of cAMP to relieve dermatitis-associated itching. E-6005 may be a promising novel therapeutic agent with antipruritic activity for the treatment of AD. E-6005 is currently in phase 2 development for patients with mild-to-moderate atopic dermatitis.

LY3023414, an investigational drug, is a small molecule that that demonstrates activity against PI3K, mTOR, and DNA-PK in tumor cells, thereby inducing cell-cycle effects and inhibiting cancer cell viability. As shown in vitro LY3023414 inhibits the ability of PI3K and mTOR to phosphorylate substrates in the PI3K/mTOR pathway, one of the most frequently mutated pathways in cancer, leading to cancer progression and resistance to existing treatments. Downstream target inhibition by LY3023414 occurs rapidly via an intermittent “on/off” mechanism that may enhance the drug's clinical tolerability, which may in turn allow LY3023414 to overcome some of the toxicities associated with PI3K/mTOR inhibitors and potentially reduce the emergence of feedback mechanisms leading to resistance. The physicochemical and absorption properties of LY3023414 are favorable, as evidenced by the molecule's high solubility across a wide pH range and high oral bioavailability. On the basis of these findings, LY3023414 is currently being evaluated in clinical trials in patients with advanced cancer such as metastatic prostate cancer and non-small cell lung cancer in combination with other chemotherapeutic agents and in endometrial cancer as a monotherapy.

AL 102 (previously known as BMS 986115), was developed as an orally active a gamma-secretase and pan-Notch inhibitor. The drug participated in phase I clinical trials in solid tumor patients. The drug was safe and well-tolerated and stabilized disease for more than six months in 14% of patients, however, Bristol-Myers Squibb terminated the study because of the changes in the business objectives. Ayala, an Israeli biotech company, licensed rights for the development of AL 102 from Bristol-Myers Squibb. In December 2018, Ayala in collaborating with Novartis decided to investigate AL102 for treatment of multiple myeloma. Ayala studied AL102, an inhibitor of the Notch pathway, in blood cancers. It is known that the pathway regulates cell-fate determination during development and maintains adult tissue balance. Cumulative evidence indicates that Notch is overactive in multiple myeloma and participates in its onset and progression.

CC-122 is the first-in-class pleiotropic pathway modifiers that may work by binding cereblon and promoting the ubiquitination and the resulting degradation of the transcription factors Aiolos and Ikaros. It has been shown to have potent anti-proliferative, anti-angiogenic and immunomodulatory activities in B cell lymphoma, perhaps though its T and NK-cell activation and B-cell inhibition. CC-122 inhibits proliferation and induces apoptosis in a broad panel of diffuse large B-cell lymphoma cell lines, reduces tumor growth in xenograft models established from activated B-cell (ABC) and germinal center B-cell DLBCL cell lines, and stimulates IL-2 production in primary T cells. These activities are dependent on the binding of CC-122 to Cereblon and subsequent ubiquitination and proteasomal degradation of Aiolos and Ikaros, resulting in direct derepression of interferon (IFN)–stimulated gene (ISG) transcription and induction of IFN-inducible proteins, ultimately leading to apoptosis.

Vilaprisan, a small molecule progesterone receptor antagonist is being developed by Bayer HealthCare Pharmaceuticals (formerly Bayer Schering Pharma) for the treatment of endometriosis and uterine leiomyoma. Hormonal imbalance observed in women with endometriosis is a potential target for treating endometriosis. Vilaprisan is a highly selective steroidal progesterone receptor modulator (SPRM). It is a partial agonist of progesterone receptor, which means that the drug activates progesterone receptors to a certain degree upon binding. This triggers a cascade of biochemical reactions that result in the suppression of prostaglandin production. This, in turn, relieves symptoms such as pain and bleeding. Modulating progesterone by taking vilaprisan might help in treating endometriosis over the long term. Phase I and II studies give encouraging results on the efficacy of vilaprisan at different doses. Like other SPRMs, vilaprisan induces benign changes of endometrium (PR modulator-associated endometrial changes, PAECs). These disappear as treatment is discontinued. Unlike GnRHa treatment, neither UPA nor vilaprisan induce hypoestrogenism and associated symptoms. Phase III studies are ongoing to confirm efficacy and safety of vilaprisan in long-term treatment of symptomatic fibroids.

Novartis Oncology (previously Novartis) is developing nazartinib (formerly EGF 816), a third generation mutant-selective tyrosine kinase inhibitor (TKI) of epidermal growth factor receptor (EGFR), for the treatment of solid malignancies, with a focus on non-small cell lung cancer. Nazartinib is a covalent mutant-selective EGFR inhibitor, with Ki and Kinact of 31 nM and 0.222 min−1 on EGFR(L858R/790M) mutant, respectively. Upon oral administration, nazartinib covalently binds to and inhibits the activity of mutant forms of EGFR, including the T790M EGFR mutant, thereby preventing EGFR-mediated signaling. This may both induce cell death and inhibit tumor growth in EGFR-overexpressing tumor cells. EGFR, a receptor tyrosine kinase mutated in many tumor cell types, plays a key role in tumor cell proliferation and tumor vascularization. EGF816 preferentially inhibits mutated forms of EGFR including T790M, a secondarily acquired resistance mutation, and may have therapeutic benefits in tumors with T790M-mediated resistance when compared to other EGFR tyrosine kinase inhibitors. As this agent is selective towards mutant forms of EGFR, its toxicity profile may be reduced as compared to non-selective EGFR inhibitors which also inhibit wild-type EGFR.

Hyoscyamine methylbromide, a muscarinic acetylcholine receptor antagonist, was studied as an antispasmodic.