Delving into the Latest Updates on SMP-028 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

LTRs x TBXA2R

Action

antagonists

Mechanism

LTRs antagonists(Leukotriene receptor antagonists), TBXA2R antagonists(Thromboxane A2 receptor antagonists)

Therapeutic Areas

Immune System DiseasesInfectious DiseasesOtorhinolaryngologic Diseases+ [1]

Active Indication-

Inactive Indication

AsthmaRhinitis, Allergic

Originator Organization

Sumitomo Pharma Co., Ltd.

Active Organization-

Inactive Organization

Sumitomo Pharma Co., Ltd.

License Organization-

Drug Highest PhaseDiscontinuedPhase 1

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC23H26FN5O2S

InChIKeyNBGPMRBRSOZDOV-UHFFFAOYSA-N

CAS Registry914389-14-3

SMP-028 is a drug candidate developed for the treatment of asthma. In a 13-week repeated dose toxicity study of SMP-028 in rats and monkeys, differences of endocrine toxicological events between rats and monkeys were observed. In rats, these toxicological events mainly consisted of pathological changes in the adrenal, testis, ovary, and the other endocrine-related organs. On the other hand, in monkeys, no toxicological events were observed. The goal of this study is to try to understand the reason why only rats, but not monkeys, showed toxicological events following treatment with SMP-028 and to eventually predict the possible toxicological effect of this compound on human endocrine organs. Our results show that SMP-028 inhibits neutral cholesterol esterase more strongly than other steroidogenic enzymes in rats. Although SMP-028 also inhibits monkeys and human neutral cholesterol esterase, this inhibition is much weaker than that of rat neutral cholesterol esterase. These results indicate (1) that the difference in endocrine toxicological events between rats and monkeys is mainly due to inhibition of steroidogenesis by SMP-028 in rats, not in monkeys, and (2) that SMP-028 may not affect steroidogenesis in humans and therefore might cause no endocrine toxicological events in clinical studies.

01 Apr 2014·Toxicology in VitroQ3 · MEDICINE

Effect of SMP-028 on steroidogenesis in rats; mechanism of toxicological events on endocrine organs of rats

Q3 · MEDICINE

Article

Author: Nishizato, Yohei ; Okahashi, Noriko ; Yabunaka, Atsushi ; Kunimatsu, Takeshi ; Yabuki, Masashi ; Imai, Satoki

SMP-028 is a new compound for treatment of asthma. Oral administration of SMP-028 to rats was associated with toxicological events in endocrine organs. These events mainly consisted of pathological changes in the adrenal gland, testis, prostate, seminal vesicle, ovaries, and uterus. In this study, we set to clarify whether SMP-028 inhibits steroidogenesis in primary culture cells obtained from rat endocrine organs in vitro. Adrenal cells, testicular cells, and ovarian cells were treated with SMP-028 and the production of steroid hormones, i.e., progesterone, aldosterone, corticosterone, total testosterone, and estradiol from these cells was measured by radioimmunoassay. We found that the production of progesterone from these cells treated with SMP-028 at 1 μM decreased to 16-67% that of the control. These findings indicate that SMP-028 inhibits steroidogenesis in rat endocrine organs in vitro. Considering that free maximum concentration in rats treated with SMP-028 are higher than the IC50 values for the inhibition of steroidogenesis in vitro, it is therefore believed that the toxicological events seen in rats following treatment with SMP-028 are due to inhibition of steroidogenesis in vivo.

100 Deals associated with SMP-028

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Asthma	Phase 1	United Kingdom	Sumitomo Pharma Co., Ltd.	-
Asthma	Phase 1	United States	-	-
Asthma	Phase 1	Netherlands	Sumitomo Pharma Co., Ltd.	-
Asthma	Phase 1	Japan	Sumitomo Pharma Co., Ltd.	-
Rhinitis, Allergic	Phase 1	United Kingdom	Sumitomo Pharma Co., Ltd.	-