HDAC1 inhibitors(Histone deacetylase 1 inhibitors), HSP90 inhibitors(Heat shock 90kDa proteins inhibitors), KDM1A inhibitors(Lysine-specific histone demethylase 1 inhibitors)

+ [1]

Therapeutic Areas

NeoplasmsUrogenital Diseases

Active Indication

Prostatic Cancer

Inactive Indication-

Originator Organization

University of Toledo

Active Organization

University of Toledo

Inactive Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

100 Clinical Results associated with IND-2

100 Translational Medicine associated with IND-2

100 Patents (Medical) associated with IND-2

Literatures (Medical) associated with IND-2

Pharmaceuticals

Thermal Compatibility of New ACEI Derivatives with Popular Excipients Used to Produce Solid Pharmaceutical Formulations

Article

Author: Wacławek, Stanisław ; Szczolko, Wojciech ; Broncel, Mateusz ; Kowalski, Oskar ; Juszczak, Anna ; Białek-Dratwa, Agnieszka ; Ramos, Paweł ; Silvestri, Daniele

Background/Objectives: Increasing drugs’ stability and adequately protecting them against degradation will ensure a decrease in their price and broader availability of pharmaceutical substances. This is of great importance, especially for drugs used to treat the most common diseases in the population, such as hypertension. The study examined two newly synthesized substances from the angiotensin I-converting enzyme inhibitor (ACEI) group as potential drugs. ACEIs are among the leading drugs used in the treatment of hypertension in the world. The chemical modifications of the tested substances applied concerned the places most susceptible to degradation. The presented work analyzed the compatibility of new derivatives with selected excipients used in pharmacy. Methods: Thermogravimetric (TGA) and differential thermal analyses (c-DTA) were used as the main methods. In addition, non-thermal methods such as colorimetry analysis, Fourier-transform infrared (FTIR) and UV spectroscopy were used. Results: Based on the conducted studies, it can be concluded that the incompatibility of IND-1 with glucose anhydrous and lactose monohydrate occurs only when the mixture is stored at higher temperatures. For the remaining IND-1 and IND-2 mixtures with excipients, compatibility was demonstrated. Conclusions: The obtained results confirmed the usefulness of the applied thermal analyses (TGA and c-DTA) for assessing the compatibility of the tested potential drugs with excipients. However, in the case of incompatibility reactions of substances occurring under the influence of elevated temperatures, such as the Maillard reaction, it is necessary to use non-thermal methods to obtain the right result.

Cancer Science

Nelarabine‐combined chemotherapy improves outcome of T‐cell acute lymphoblastic leukemia but shows more severe neurotoxicity: JALSG T‐ALL213‐O

Article

Author: Sato, Shinya ; Saito, Takeshi ; Imai, Kiyotoshi ; Sakaida, Emiko ; Yamazaki, Etsuko ; Hayakawa, Fumihiko ; Miyazaki, Yasushi ; Matsumura, Itaru ; Murayama, Tohru ; Yokoyama, Yasuhisa ; Ishikawa, Yuichi ; Katsuoka, Yuna ; Kiyoi, Hitoshi ; Hatta, Yoshihiro ; Mori, Naoki ; Atsuta, Yoshiko

AbstractWe investigated the effectiveness and safety of nelarabine (NEL)‐combined chemotherapy for newly diagnosed adult T‐cell acute lymphoblastic leukemia (T‐ALL) patients. We conducted a phase II trial, T‐ALL213‐O, where adult T‐ALL patients aged 25 to 64 were treated by a regimen based on that used in our previous study, ALL202‐O. The main modifications from ALL202‐O to T‐ALL213‐O were as follows: (1) NEL‐combined chemotherapy, instead of consolidation (C)1, was used for non‐complete remission (CR) patients after induction therapy (IND)1 as IND2; (2) NEL treatments were inserted into C3 and C5 on day 29. Twenty‐four patients were analyzed. Ten patients did not receive NEL treatment due to therapy termination prior to C3. Three‐year event‐free survival (EFS) was 70%, with 52% as the lower limit of its 90% confidence interval, which exceeded the threshold of 25%; thus, the study treatment was considered effective. The CR rates by IND1, IND2, and both were 75%, 100%, and 88%, respectively. The 5‐year EFS and 5‐year overall survival rates were 66% and 70%, respectively, with median follow‐ups of 7.7 and 7.8 years. The addition of NEL improved the CR rate but not survival, compared with T‐ALL patients in ALL202‐O. Severe neuropathy after NEL administration was observed at a high frequency. Seven (50%) of 14 patients treated with NEL showed grade 3 peripheral neuropathy and/or gait disturbance. The neurotoxicity was considered stronger than that previously reported. Combination therapy of NEL at this dose and intensive multidrug chemotherapy is associated with a high risk of severe neurotoxicity (JALSG T‐ALL213‐O, UMIN000010642).

100 Deals associated with IND-2

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Prostatic Cancer	Preclinical	US	University of Toledo	04 Apr 2023

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