3-Indolepropionic acid (IN-OX1; Indole-3-propionic acid; OX-1; Oxigon; SHP 22; SHP-622; VP-20629), an endogenous substance produced by bacteria in the intestine, is a deamination product of Tryptophan (T947200) that protects the hippocampus (studied in gerbils) from ischemic damage and oxidative stress. It’s ability to protect the neurons in this way is attributed to its potent antioxidative effects. 3-Indolepropionic acid is also hypothesized to have protective effects on the thyroid gland. 3-Indolepropionic acid is being studied for therapeutic use in Alzheimer's disease. 3-Indolepropionic acid (IPA) completely protected primary neurons and neuroblastoma cells against oxidative damage and death caused by exposure to Abeta, by inhibition of superoxide dismutase, or by treatment with hydrogen peroxide. In kinetic competition experiments using free radical-trapping agents, the capacity of IPA to scavenge hydroxyl radicals exceeded that of melatonin, an indoleamine considered to be the most potent naturally occurring scavenger of free radicals. In contrast with other antioxidants, IPA was not converted to reactive intermediates with pro-oxidant activity. In 2011, Intellect redirected the focus of the OX1 program from Alzheimer's disease to FA (Friedreich's Ataxia). Research suggests that the symptoms associated with FA are the result of oxidative stress caused by the abnormal accumulation of iron. OX1's ability to neutralize ROS could be an effective agent to reduce oxidative stress in FA, thereby eliminating the symptoms of FA and increasing both quality of life and longevity in affected individuals.

Norlevorphanol is the levo-isomer of 3-hydroxymorphinan (morphinan-3-ol). It is is an opioid analgesic of the morphinan family. Norlevorphanol is a Schedule I controlled substance (opiate).

Alseres Pharmaceuticals is developing an 123I-labelled imaging agent, Altropane®, as a diagnostic aid in Parkinson's disease and other movement disorders. Altropane is a molecular-imaging agent that specifically binds to the dopamine transporter (DAT) protein found on the surface of dopamine-producing neurons, making it visible during SPECT imaging. Since most forms of Parkinsonian Syndromes result in a decreased number of dopamine-producing cells, it would be expected that these patients also have fewer DATs than do patients without PS. Thus, it is believed that altropane used in conjunction with SPECT imaging could be a useful test to distinguish Parkinsonian Syndrome tremors from non-Parkinsonian tremor: non-Parkinsonian patients would have more altropane-binding visible in the SPECT image, while Parkinsonian patients would have less. The E isomer of (123)I-2beta-carbomethoxy-3beta-(4-fluorophenyl)-N-(1-iodoprop-1-en-3-yl)nortropane (Altropane(R)) shows high affinity (IC(50) = 6.62 +/- 0.78 nmol) and selectivity (DA/5-HT = 25) for DAT sites in the striatum. Altropane is presently in Phase III clinical development for the diagnosis of Parkinson's disease.

SNS-032 (formerly BMS-387032) is a potent, selective inhibitor of cyclin-dependent kinases (CDK). SNS-032 blocks the cell cycle via inhibition of CDKs 2 and 7, and transcription via inhibition of CDKs 7 and 9. SNS-032 was investigated for the treatment of solid tumors and hematologic malignancies (Phase I studies), however, its development was discontinued.

10-Hydroxycamptothecin (10-HCPT), an indole alkaloid isolated from a Chinese tree, Camptotheca acuminate, inhibits the activity of topoisomerase I and has a broad spectrum of anticancer activity in vitro and in vivo. However, its use has been limited due to its water-insolubility and toxicity with i.v. administration. Prolonged elimination of 10-HCPT in vivo may have a significant impact on its therapeutic effects. 10-HCPT is metabolized to its carboxylate form and glucuronides.It was investigated that relatively low dose of 10-HCPT is able to inhibit the growth of colon cancer, facilitating the development of a new protocol of human trials with this anticancer drug.

IPI-493 (17-AG, 17-Aminogeldanamycin) is the major metabolite of tanespimycin (17-AAG) and retaspimycin (17-DMAG) with potent antineoplastic activity. Hsp90 controls the proper folding, function, and stability of various "client" proteins within cells. Many of the clients of Hsp90 (such as Akt, Bcr-Abl, EGFR, Flt-3, c-Kit and PDGFR α) are oncoproteins or important cell-signaling proteins, and therefore are critical for tumor cell growth and survival. Inhibition of Hsp90 results in degradation of these proteins, which abrogates growth and survival signaling and leads to tumor cell death. IPI-493 has been used in trials studying the treatment of Advanced Malignancies.

Selurampanel (previously known as BGG 492), an orally available, AMPA-type glutamate receptor (AMPAR)/kainate receptor (GluK1; GluR5) antagonist was developed by Novartis. It is known that AMPAR antagonism is under development as a novel mechanism of action for antiepileptic drugs. Selurampanel was studied in phase II clinical trial for the migraine treatment. However, Proof-of-concept criterion was not met. In addition, the drug also participated in phase II clinical trials in therapy-refractory partial seizures for epilepsy surgery and in patients with chronic subjective tinnitus. Development of selurampanel for all these diseases was discontinued as of September 2017.

E-7820 is a novel angiogenesis inhibitor. It inhibited in vitro proliferation and tube formation of human umbilical vascular endothelial cell (HUVEC). E-7820 decreased integrin alpha 2, 3, 5, and beta 1 in confluent culture of HUVEC, and integrin alpha 2 was initially suppressed in mRNA level, followed by decrement of integrins alpha 3, 5, and beta 1. Up-regulation of integrin alpha2 by phorbol 12-myristate 13-acetate abrogated the inhibitory effect of E7820 on tube formation within type I collagen gel, whereas addition of antibody against integrin alpha2 canceled the phorbol 12-myristate 13-acetate effect. This finding may provide the basis for a new approach to antiangiogenic therapy through the suppression of integrin alpha2 on endothelium. E-7820 showed a broad-spectrum antitumor effect in mice through inhibition of angiogenesis and indicate that the decrease of integrin alpha2 on platelets might serve as a biological marker for the antitumor efficacy of E-7820. Combining E-7820 and chemotherapeutic agents to block the integrin α2β1/PI3K/AKT/Snail signaling pathway revealed dramatically enhanced tumor suppression and provided an innovative approach for clinical colorectal cancer treatment.

Epofolate (BMS-753493) is a folate conjugate of the epothilone analog BMS-748285 that was designed to selectively target folate receptor expressing cancer cells. In Phase I/IIa pharmacokinetic and safety studies epofolate was generally tolerable and toxicities known to be associated with epothilone class of anticancer agents were common, although peripheral neuropathy and neutropenia appear to have been less frequent and less severe as compared to epothilones. Antitumor activity was not demonstrated and further development of BMS-753493 has been discontinued.