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更新于：2026-01-31
Balipodect
更新于：2026-01-31
概要
基本信息
在研机构- |
权益机构- |
最高研发阶段无进展临床2期 |
首次获批日期- |
最高研发阶段(中国)- |
特殊审评孤儿药 (美国)、孤儿药 (欧盟) |
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结构/序列
分子式C23H17FN6O2 |
InChIKeyKVHRYLNQDWXAGI-UHFFFAOYSA-N |
CAS号1238697-26-1 |
关联
4
项与 Balipodect 相关的临床试验NCT02477020
A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Parallel-group, 6-Week Study to Evaluate the Efficacy and Safety of TAK-063 in Subjects With an Acute Exacerbation of Schizophrenia
NCT02370602
An Open-Label [^11C]T-773 Positron Emission Tomography Study to Determine Phosphodiesterase10A Occupancy by TAK-063 After a Single Oral Dose in Human Volunteers
NCT01892189
A Randomized, Investigator and Subject-Blind, Placebo-Controlled, Single-Dose, 3-Period, Incomplete Block Cross-Over Study to Evaluate the Effects of Single Oral Administration of TAK-063 on Preventing Ketamine-Induced Brain Activity Changes as Well as Psychotic-Like Symptoms in Healthy Male Adults
100 项与 Balipodect 相关的临床结果
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100 项与 Balipodect 相关的转化医学
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100 项与 Balipodect 相关的专利（医药）
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29
项与 Balipodect 相关的文献（医药）2025-02-11REPRODUCTION
Potent and sustained enhancement of human sperm motility using novel cyclic AMP upregulators
Article
作者: Marín-Briggiler, Clara I ; Otero, Patricia ; Ferrulli, Mariana ; Minotti, Florencia ; Buffone, Mariano G ; Luque, Guillermina M ; Lavolpe, Mariano ; Oscoz-Susino, Natalia ; Krapf, Dario
In brief:
The cyclic adenosine monophosphate (cAMP) pathway is essential for maintaining sperm physiology. This study examines a cAMP analog and a phosphodiesterase inhibitor that effectively enhance human sperm motility, thereby improving the efficiency of
in vitro
sperm selection.
Abstract:
cAMP plays a central role in sperm physiology. Various cAMP upregulators, both cAMP analogs and phosphodiesterase (PDE) inhibitors, have been used in handling human sperm
in vitro
, although conflicting results and variable responses among patients have been reported. This study aims to evaluate the ability of two compounds – Sp-5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole 3′-5′-cyclic monophosphothioate (cBiMPs), a cAMP analog, and TAK-063, a specific PDE10A inhibitor – to enhance human sperm motility parameters and, consequently, improve sperm preparation procedures. Our results showed that both cBiMPs and TAK-063 significantly enhanced human sperm motility and hyperactivation compared to the control (dimethyl sulphoxide). They also increased protein phosphorylation levels without inducing premature acrosomal exocytosis or DNA fragmentation. The enhancement of sperm motility persisted for 4 h after their removal, surpassing the effects of known cAMP analogs (8-bromo-adenosine-3′, 5′-cAMP (8-Br-cAMP) or dibutyryl cAMP (db-cAMP)) or PDE inhibitors (3-isobutyl-1-methylxanthine (IBMX) or pentoxifylline (PTX)). Furthermore, the presence of cBiMPs or TAK-063 during sperm selection resulted in higher recovery rates in comparison to the control, and these compounds effectively improved sperm motion in both fresh and cryopreserved samples with impaired motility. In conclusion, cBiMPs and TAK-063 exhibit potent and sustained effects on human sperm motility, enhancing the efficiency of sperm preparation techniques. The ability to improve sperm motility holds significant implications for male infertility treatment, facilitating the use of low complexity techniques such as intrauterine insemination or
in vitro
fertilization, and may also aid in selecting viable testicular sperm for intracytoplasmic sperm injection.
2025-02-01ANESTHESIOLOGY
Inhibition of Phosphodiesterase 10A Alleviates Pain-like Behavior in Mice
Article
作者: Kallenborn-Gerhardt, Wiebke ; Gerninghaus, Hannah ; Hernandez-Olmos, Victor ; Petersen, Jonas ; Schmidtko, Achim ; Feil, Susanne ; Sinderwald, Rekia ; Stehle, Daniel ; Proschak, Ewgenij ; Duman, Emre ; Feil, Robert ; Lu, Ruirui ; Nagel, Chantal ; Metzner, Katharina ; Gross, Tilman ; Zhou, Fangyuan
Background::
Emerging evidence indicates that cyclic nucleotide phosphodiesterases exert distinct functions in pain processing and that targeting phosphodiesterases might be a novel strategy for pain relief. This study hypothesized that the phosphodiesterase isoform phosphodiesterase 10A (PDE10A) might be a target for analgesic therapy.
Methods::
In situ hybridization, immunostaining, cyclic nucleotide enzyme immunoassays, real-time cyclic guanosine monophosphate imaging, and real-time quantitative reverse transcription polymerase chain reaction were performed to investigate the expression and activity of PDE10A in the dorsal root ganglia and spinal cord. Mice of both sexes were assessed in multiple pain models after the administration of specific PDE10A inhibitors.
Results::
PDE10A is distinctly expressed in nociceptive neurons in the dorsal root ganglia and spinal cord of mice. Incubation of cultured sensory neurons with the PDE10A inhibitor, TAK-063 (150 nM), increased cyclic guanosine monophosphate levels in enzyme immunoassays and real-time imaging at the single-cell level. Strikingly, treatment with TAK-063 (0.3 mg/kg intraperitoneal) ameliorated the pain-like behavior of female and male mice in models of acute nociceptive pain after intraplantar injection of capsaicin (mean ± SD, 8.87 ± 8.78 s [TAK-063] vs. 51.24 ± 36.36 s [vehicle], P = 0.020) or allyl isothiocyanate (2.46 ± 3.43 s [TAK-063] vs. 10.36 ± 4.87 s [vehicle]; P = 0.018). Furthermore, TAK-063 (0.3 mg/kg intraperitoneal) reduced established pain-like behavior in models of inflammatory pain induced by intraplantar injection of zymosan (two-way ANOVA, group, F[1,18] = 48.51, TAK-063 vs. vehicle; P ≤ 0.0001) or complete Freund’s adjuvant (F[1,14] = 46.10, TAK-063 vs. vehicle; P ≤ 0.0001), without the development of antinociceptive tolerance. The antinociceptive effects were recapitulated using the PDE10A inhibitor PF-2545920.
Conclusions::
Collectively, the data support the idea that PDE10A is a suitable target for the development of efficacious analgesic drugs.
2024-12-01MOLECULAR AND CELLULAR NEUROSCIENCE
Inhibition of phosphodiesterase 10A mitigates neuronal injury by modulating apoptotic pathways in cold-induced traumatic brain injury
Article
作者: Ozpinar, Aysenur ; Altintas, Mehmet O ; Kilic, Ertugrul ; Beker, Mustafa C. ; Bayraktaroglu, Cigdem ; Beker, Mustafa C ; Sengun, Nursena ; Altintas, Mehmet O. ; Dogan, Enes ; Balaban, Buse ; Altunay, Serdar
Brain injury develops from a complex series of pathophysiological phases, resulting in acute necrotic or delayed apoptotic cell death after traumatic brain injury (TBI). Inhibition of apoptotic cell death is critical for the treatment of acute neurodegenerative disorders, such as TBI. Here, we investigated the role of phosphodiesterase 10A (PDE10A) in the development of neuronal injury, particularly in apoptotic cell death. Using the PDE10A inhibitor TAK-063, we found that PDE10A inhibition is associated with decreased brain injury, brain swelling, and blood brain barrier disruption 48 h after cold-induced TBI. Furthermore, a particularly notable result was observed with 3 mg/kg TAK-063, which reduced disseminated neuronal injury. Protein abundance analysis revealed that PDE10A inhibition activates survival kinases AKT and ERK-1/-2, which were associated with the decreased activation of MMP-9 and PTEN. Additionally, iNOS and nNOS levels significantly reduced in the TAK-063 group, playing roles in inflammation and apoptosis. A planar surface immunoassay was performed for in-depth analyses of the apoptotic signaling pathways. We observed that inhibition of PDE10A resulted in the decreased expression of TNFRSF1A, TNFRSF10B, and TNFRSF6 receptors, particularly inducing apoptotic cell death. Moreover, these findings correlated with reduced levels of pro-apoptotic proteins, including PTEN, p27, Cytochrome-c, cleaved Caspase-3, Bad, and p53. Interestingly, TAK-063 treatment reduced levels of anti-apoptotic proteins or enzymes, including XIAP, Claspin, and HIF1α, without affecting Bcl-x, MCL-1, SMAC, HO-1, HO-2, HSP27, HSP60, and HSP70. The findings suggest that PDE10A regulates cellular signaling predominantly pro-apoptotic pathways, and inhibition of this protein is a promising approach for the treatment of acute brain injury.
100 项与 Balipodect 相关的药物交易
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研发状态
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| 适应症 | 最高研发状态 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|---|
| 精神分裂症 | 临床2期 | 美国 | 2015-07-01 | |
| 精神障碍 | 临床1期 | 美国 | 2013-08-01 |
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临床结果
临床结果
适应症
分期
评价
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临床1期 | - | 27 | 鏇鏇艱餘獵夢鏇構築願(遞淵遞膚鏇蓋網網鏇齋) = brain activity 範鏇鹽糧選餘簾顧鏇蓋 (糧簾鏇範鏇觸糧夢鹹襯 ) | 积极 | 2020-02-01 | ||
临床2期 | 164 | 觸構願遞鹽糧顧醖夢壓(夢蓋窪壓餘範壓膚齋廠) = not achieved 淵鬱範繭製獵鏇夢廠積 (鑰築鑰壓繭鹹鏇選窪簾 ) 更多 | 不佳 | 2019-02-01 | |||
Placebo | |||||||
临床2期 | 164 | 鹹獵願繭壓窪齋網憲艱(糧獵遞鑰鹹範鬱積壓觸) = 構選選鏇觸鑰網鏇醖鑰 範糧製選鏇艱壓築願鹹 (構積蓋鏇襯製積餘構築 ) 更多 | - | 2018-06-01 | |||
临床2期 | 164 | Placebo | 鹽網膚選築膚餘齋鏇範(願醖窪糧膚窪衊鏇窪膚) = 廠網鑰築餘膚鹹築願積 襯鹽製齋選襯襯鹹齋簾 (窪壓淵築簾製繭獵製製, 2.474) 更多 | - | 2017-09-29 | ||
临床1期 | 27 | 鬱簾鹹鏇構蓋觸廠壓繭(衊網窪蓋餘觸築築壓壓) = 襯窪獵構簾選壓網餘廠 鬱範衊糧顧繭鏇願築夢 (膚網鬱簾壓觸繭鏇築選, 0.53382) 更多 | - | 2017-01-12 | |||
(TAK-063 3 mg) | 鬱簾鹹鏇構蓋觸廠壓繭(衊網窪蓋餘觸築築壓壓) = 醖廠夢範壓構繭鹽糧淵 鬱範衊糧顧繭鏇願築夢 (膚網鬱簾壓觸繭鏇築選, 0.67925) 更多 | ||||||
临床1期 | 84 | 鏇鹹觸夢顧觸糧壓獵鑰(鹽構繭築憲膚襯襯鹹顧) = The most common drug-related adverse events (AEs) were somnolence (33.3 %), orthostatic tachycardia (19.7 %), and orthostatic hypotension (9.1 %). 積齋鹹範獵衊選積衊獵 (獵選膚醖窪鬱積齋簾願 ) | 积极 | 2016-10-01 | |||
Placebo | |||||||
临床1期 | - | 13 | (TAK-063 3 mg + [^11C]T-773) | 廠觸網鏇窪製膚醖鹹築(窪醖壓糧膚齋遞構窪觸) = 齋範憲鏇積鬱範鏇觸鏇 鏇壓窪夢鬱築憲鏇膚蓋 (齋觸蓋製鹽艱齋糧糧廠, 16.4049) 更多 | - | 2015-03-20 | |
(TAK-063 10 mg) | 廠觸網鏇窪製膚醖鹹築(窪醖壓糧膚齋遞構窪觸) = 積簾憲壓顧鹹壓淵蓋艱 鏇壓窪夢鬱築憲鏇膚蓋 (齋觸蓋製鹽艱齋糧糧廠, 2.4749) |
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