Therapeutic effect of TAC‐302, a cyclohexenoic fatty alcohol derivative, on bladder denervation‐related storage and voiding dysfunctions in rats

Yoshida, Shohei; Noma, Takahisa; Miyoshi, Kazuhisa; Tsukihara, Hiroyuki; Orimoto, Naoki; Hakozaki, Atsushi; Sasaki, Eiji

doi:10.1002/nau.23571

Cited by 9 publications

(12 citation statements)

References 26 publications

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“…Taiho Pharmaceutical Co's TAC-302 is a cyclohexenoic fatty alcohol derivative that can promote neurite outgrowth in isolated peripheral neurons and prevents bladder denervation related bladder dysfunctions following BOO in rats [19,20]. In preclinical studies, TAC-302 improved storage and voiding dysfunctions by improving bladder denervation and detrusor underactivity (DU) even when the treatment was started after storage and voiding dysfunctions had already occurred [21].…”

Section: Tac-302mentioning

confidence: 99%

Underactive Bladder; Review of Progress and Impact From the International CURE-UAB Initiative

et al. 2020

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There is a significant need for research and understanding of underactive bladder (UAB). The International Congress of Urologic Research and Education on Aging UnderActive Bladder (CURE-UAB) was organized by Doctors Michael Chancellor and Ananias Diokno in order to address these concerns. CURE-UAB was supported, in part, by the US National Institute of Aging and National Institute of Diabetes Digestive and Kidney. Since 2014, there have been 5 successful CURE-UAB congresses. They have brought together diverse stakeholders in the UAB field to identify areas of major scientific challenge and initiated a call to action among the medical community. In this review, we will highlight current and novel treatments under development for UAB and the progress and impact from the CURE-UAB initiative.

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Section: Tac-302mentioning

confidence: 99%

Underactive Bladder; Review of Progress and Impact From the International CURE-UAB Initiative

et al. 2020

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“…TAC‐302 3‐(15‐hydroxypentadecyl)‐2,4,4‐trimethyl‐2‐cyclohexen‐1‐one is a novel and potent cyclohexenonic long‐chain fatty alcohol derivative that stimulates neurite outgrowth activity in cultured neurons . It has been reported that cyclohexenoic long‐chain fatty alcohol improved bladder function in rats . Via such neurotrophic activity, TAC‐302 is expected to counteract partial denervation of the bladder and lower urinary tract tissue and restore urinary function .…”

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confidence: 99%

“…5 It has been reported that cyclohexenoic long-chain fatty alcohol improved bladder function in rats. [6][7][8] Via such neurotrophic activity, TAC-302 is expected to counteract partial denervation of the bladder and lower urinary tract tissue and restore urinary function. 9 Based on the nonclinical data, the estimated main elimination pathway of TAC-302 is metabolism, and a hydroxyl group of TAC-302 was metabolized to the carboxylic acid.…”

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confidence: 99%

Safety, Tolerability, Pharmacokinetics, and Food Effects on TAC‐302 in Healthy Participants: Randomized, Double‐Blind, Placebo‐Controlled, Single‐Dose and Multiple‐Dose Studies

Sesoko

Huang

Okayama

et al. 2020

Clinical Pharm in Drug Dev

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TAC-302 stimulates neurite outgrowth activity and is expected to restore urinary function in patients with lower urinary tract dysfunction. We conducted 2 phase 1, randomized, placebo-controlled studies to confirm the safety and pharmacokinetics (PK) of TAC-302 in healthy adult Japanese male volunteers. In the first-inhuman single-dose study (n = 60), TAC-302 was administered at doses from 100 to 1200 mg after an overnight fast. The effects of a meal on the PK of TAC-302 400 mg were also examined. A multiple-dose study (n = 36) evaluated the effects of meal fat content on the PK of single doses of TAC-302 (100, 200, or 400 mg) and multiple doses of TAC-302 administered for 5 days (100, 200, and 400 mg twice daily). TAC-302 showed linear PK up to doses of 1200 mg in the fasting state, and across the dose range of 100-400 mg in the fed state. No accumulation of TAC-302 was observed. Food, particularly with high fat content, increased TAC-302 plasma concentrations. No differences were observed in the adverse event incidence between the TAC-302 and placebo groups in either study. TAC-302 showed a wide safety margin.

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“…The cyclohexenoic long fatty alcohol originally has low aqueous solubility and oral absorbability because of high lipophilicity. Therefore, to make it orally available, we developed new formulations of this compound either by cocrystalizing with palmitic acid in the first paper or by mixing with Gelucire® in the second paper . We think this achievement is important to advance this compound into clinical use.…”

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confidence: 99%

The response to Letter to the Editor “TAC‐302 promotes neurite outgrowth of isolated peripheral neurons and prevents bladder denervation related bladder dysfunctions following bladder outlet obstruction in rats” and “Therapeutic effect of TAC‐302, a cyclohexenoic fatty alcohol derivative, on bladder denervation‐related storage and voiding dysfunctions in rats”

Dmochowski¹

2019

Neurourology and Urodynamics

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Therapeutic effect of TAC‐302, a cyclohexenoic fatty alcohol derivative, on bladder denervation‐related storage and voiding dysfunctions in rats

Abstract: TAC-302 improved storage and voiding dysfunctions by improving bladder denervation and detrusor underactivity even when the treatment was started after storage and voiding dysfunctions had already occurred.

Cited by 9 publications

References 26 publications

Underactive Bladder; Review of Progress and Impact From the International CURE-UAB Initiative

Underactive Bladder; Review of Progress and Impact From the International CURE-UAB Initiative

Safety, Tolerability, Pharmacokinetics, and Food Effects on TAC‐302 in Healthy Participants: Randomized, Double‐Blind, Placebo‐Controlled, Single‐Dose and Multiple‐Dose Studies

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