Idasanutlin (RG-7388) is a second-generation, orally bioavailable, selective p53-MDM2 antagonist. MDM2 is an important negative regulator of the p 53 tumor suppressor and is expressed at high levels in a large proportion of acute myeloid leukemia (AML). Blocking the MDM2-p53 interaction stabilizes p53 and activates p-53 mediated cell death and inhibition cell growth. Idasanutlin is under clinical trial in phase III for treatment AML and in combinations with others drugs in phase I/II for treatment of multiple myeloma.

Seletalisib (UCB-5857) is a potent, ATP-competitive, and selective phosphoinositide 3-kinase (PI3K) delta inhibitor. Findings from cellular assays of adaptive immunity demonstrated that seletalisib blocks human T-cell production of several cytokines from activated T-cells. Additionally, seletalisib inhibited B-cell proliferation and cytokine release. In human whole blood assays, seletalisib inhibited CD69 expression upon B-cell activation and anti-IgE-mediated basophil degranulation. Seletalisib safety, tolerability and pharmacokinetic/pharmacodynamic profiles support its continued clinical development in immune-inflammatory diseases. UCB Pharma is developing Seletalisib for the treatment of immune and inflammatory diseases including Activated PI3K delta Syndrome (APDS), Sjogren's syndrome and psoriasis.

Phosphopantothenic acid is an amidoalkyl phosphate that is the 4-phosphate derivative of (R)-pantothenic acid. Phosphopantothenic acid is not permeable to cell membranes due to its anionic character, consistent with the observation that systemic administration of Phosphopantothenic acid does not restore CoA levels in cellular and mouse models

CB-5083 is a novel first in class, potent orally bio-available p97 inhibitor that disrupts cellular protein homeostasis and demonstrates anti-tumor activity in solid and hematological models. CB-5083 causes rapid and sustained accumulation of poly-ubiquitin in tumor xenografts after a single administration. CB-5083 showed activity to inhibit tumor growth in multiple rodent models of human cancer. Furthermore, CB-5083 appears to exhibit greater potency over current proteasome inhibitors that further validate targeting p97 and protein homeostasis in the treatment of cancer. CB-5083 is a potent inhibitor of endoplasmic reticulum associated degradation and induces a lethal unfodled protein response. CB-5083 recently began Phase 1 testing in relapsed/refractory or refractory multiple myeloma, and advanced solid tumors.

SN38 (7-ethyl-10-hydroxy camptothecin) is a prominent and efficacious anticancer agent. It is poorly soluble in both water and pharmaceutically approved solvents; therefore, the direct formulation of SN38 in solution form is limited. SN38 is formed via hydrolysis of irinotecan by carboxylesterases and metabolized via glucuronidation by UGT1A1. Currently, the water soluble prodrug of SN38, irinotecan (CPT-11), is formulated as a low pH solution and is approved for chemotherapy. SN38 causes the strongest inhibition of DNA topoisomerase I, followed by CPT and then CPT-11. CPT-11 dose dependently shifts the position of relaxed DNA in the direction of nicked DNA, but SN38 and CPT shows no effect on the position of relaxed DNA. SN38 dose-dependently and time-dependently inhibit DNA synthesis. Respective IC50 values of SN38, in DNA synthesis is 0.077 uM.

Vivolux developed VLX-1570 as a small molecule proteasome 19S proteasome deubiquitinase (DUB) inhibitor. In addition, VLX1570 shows selectivity for ubiquitin-specific protease-14 and induces apoptosis of multiple myeloma cells. VLX-1570 participated in phase I/II clinical trial in patients with myeloma. However, this study was terminated because of the dose-limiting toxicity was observed. Thus, the full clinical trial was put on hold. VLX1570 also inhibits ubiquitin carboxyl-terminal hydrolase isozyme L5 (UCHL5). Besides, was shown that VLX1570 modulated bio-cellular pathways that were essential for Waldenstrom macroglobulinemia (WM) cell survival. Thus, VLX1570 can be further studied for clinical use in patients with WM.

Veledimex is an oral activator ligand for a proprietary gene therapy promoter system, and a moderate inhibitor of and substrate for CYP3A4/5. Veledimex controls the expression of the target gene. The amount of gene product produced by the system and the duration of the effect is dependent on veledimex dose level and duration of dosing. Nonclinical studies demonstrated that intratumoral administration of Ad-RTS-IL12 along with oral administration of veledimex elicited dose-dependent anti-tumor effects in murine melanoma, breast cancer and glioma models which correlated with increased plasma exposure of veledimex. The FDA granted Fast Track designation for Ad-RTS-hIL-12 plus veledimex for the treatment of recurrent or progressive glioblastoma multiforme in adults. Ad-RTS-hIL-12 is an inducible adenoviral vector encoding human pro-inflammatory cytokine interleukin-12 (IL-12), which is under the transcriptional control of the RheoSwitch Therapeutic System. Veledixmex is an oral activator ligand. Data previously presented suggest that Ad-RTS-hIL-12 with 20 mg veledimex improves the median overall survival from 6 to 9 months seen with available therapies to 12.7 months, with further improvement in median overall survival to 17.8 months in a subset of subjects with reduced cumulative steroid exposure during the active dosing period of veledimex. Veledimex has been used in trials studying the treatment of glioblastoma multiforme, metastatic breast cancer, and anaplastic oligoastrocytoma.

ABT-751 is an orally bioavailable antimitotic sulfonamide, which binds to the colchicine-binding site on beta-tubulin and inhibits the polymerization of microtubules, leads to a block in the cell cycle at the G2M phase, resulting in cellular apoptosis. ABT-751 had been in phase Ⅱ clinical studies for the treatment of breast cancer; colorectal cancer; non-small cell lung cancer; renal cancer, prostate cancer, but these researches have been discontinued.