TAE-684 is Novartis’ first-generation inhibitor of the enzyme anaplastic lymphoma kinase with IC50 of 3 nM in a cell-free assay, which blocked the growth of ALCL-derived and ALK-dependent cell lines with IC50 values between 2 and 10 nM. TAE-684 treatment resulted in a rapid and sustained inhibition of phosphorylation of NPM-ALK and its downstream effectors and subsequent induction of apoptosis and cell cycle arrest. In vivo, TAE-684 suppressed lymphomagenesis in two independent models of ALK-positive ALCL and induced regression of established Karpas-299 lymphomas. TAE-684 also induced down-regulation of CD30 expression, suggesting that CD30 may be used as a biomarker of therapeutic NPM-ALK kinase activity inhibition. TAE-684 is also a potent inhibitor of LRRK2 kinase activity (IC(50) of 7.8nM against wild-type LRRK2. TAE-684 development was discontinued, as it formed potentially harmful protein adducts in the body.

CGP77675 is a potent Src kinase inhibitor. CGP77675 was selective toward other protein kinases: the Src kinase family members Lck and Yes were inhibited with IC50 values 20-fold higher than or equal to Src. The effect of CGP77675 on bone resorption was evaluated in vitro and in vivo. The parathyroid hormone-induced bone resorption in rat fetal long bone cultures was inhibited with an IC50 of 0.8 mmol/L. CGP77675 dose-dependently reduced the hypercalcemia induced in mice by interleukin-1b and partly prevented bone loss and microarchitectural changes in young ovariectomized rats, showing that the protective effect on bone was exerted via the inhibition of bone resorption.

Kartogenin is an activator of the smad4/smad5 pathway, and promotes the selective differentiation of multipotent mesenchymal stem cells into chondrocytes. It is promising agent for treatment of osteoarthritis.

CGP-71683A is a non-peptidic neuropeptide Y (NPY) Y5 receptor antagonist that was under development by Novartis. CGP-71683A is an extremely selective, non-peptide NPY Y5 receptor antagonist, displaying > 1000-fold selectivity over Y1, Y2 and Y4 receptors; IC50 values are 1.4, 2765, 7187 and 5637 nM at cloned rat Y5, Y1, Y2 and Y4 receptors respectively. CGP-71683A potently inhibits NPY-induced food intake following i.p. administration in diabetic, free-feeding and fasted rats.

BAG-956 is a dual PDK1 and class I PI 3-kinase inhibitor (IC50 values are 245, 56, 446, 35 and 117 nM for PDK1 and PI3K p110 -α, -β, -δ, and -γ respectively). BAG-956 has been shown to inhibit cellular AKT phosphorylation at Thr308. BAG-956 also blocks cell proliferation and causes arrest in the G1 phase of the cell cycle. BAG-956 has been shown to slow tumor progression in mouse xenograft models.

CGP-74588 (Norimatinib, N-Desmethyl Imatinib) is a metabolite of Imatinib, a tyrosine kinase inhibitor, displaying specificity for BCR-ABL. CGP-74588 is pharmacologically active, and shows a similar potency and selectivity profile as the parent drug

P-88-8991, (-)- is a metabolite of Iloperidone. It has functional affinity for noradrenergic, dopaminergic and serotoninergic receptors. Humans produce only one enantiomer stereospecifically following administration of Iloperidone. Preclinical studies revealed that P-88-8991, (-)- might be useful for the treatment of psychotic disorders such as schizophrenia and bipolar disorders.

P-88-8991, (+)- is a metabolite of Iloperidone. It has functional affinity for noradrenergic, dopaminergic and serotoninergic receptors. Humans produce only one enantiomer stereospecifically following administration of Iloperidone. Preclinical studies revealed that P-88-8991, (+)- might be useful for the treatment of psychotic disorders such as schizophrenia and bipolar disorders.

CGS -21680 is an adenosine A2 receptor agonist with IC50 of 22 nM, exhibits 140-fold over A1 receptor. In an isolated perfused working rat heart model, CGS -21680 effectively increases coronary flow with an ED25 value of 1.8 nM. CGS-21680 binds adenosine A2 receptor with high affinity (Kd = 15.5 nM). Novartis originated CGS- 21680 in Switzerland and discontinued its development later.

PKI166 is a potent and selective EGFR kinase inhibitor (IC50 = 0.7 nM). PKI166 was tested in phase I clinical trials in patients with advanced solid malignancies, where the recommended dose for further studies was 750 mg once daily for 2 weeks every 4 weeks. In preclinical model, PKI166 was tested in pancreatic, prostate, renal cell, colorectal and other types of cancer. The development of PKI166 was discontinued in 2002 after phase II clinical trials. PKI166 possess antihypertensive properties demonstrated in rat hypertensive chronic kidney disease model.