Delving into the Latest Updates on SR-16234 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

+ [1]

Target

ERα

Mechanism

ERα antagonists(Estrogen receptor alpha antagonists)

Therapeutic Areas

NeoplasmsSkin and Musculoskeletal DiseasesUrogenital Diseases

Active Indication-

Inactive Indication

Breast CancerBreast cancer recurrentEndometriosis+ [1]

Originator Organization

SRI International

Active Organization-

Inactive Organization

SRI International

Taiho Pharmaceutical Co., Ltd.Tottori University Hospital

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Structure

Molecular FormulaC33H47NO3

InChIKeyOHCPNHFLPCVWRG-MWSJHZLTSA-N

CAS Registry229634-97-3

View All Structures (2)

ProblemTo evaluate the effects of SR‐16234 (SR), a selective estrogen receptor modulator (SERM), on murine endometriosis‐like lesions.Method of studyBALB/c mice (n = 53) were used to establish the murine endometriosis model. Ovariectomized, estradiol replaced, 6‐week‐old murine endometriosis model were injected with lipopolysaccharide (LPS) with or without SR (1 mg/kg/d) or vehicle, over a period of 4 weeks. Upon treatment completion, the endometriosis‐like lesions that developed in the abdominal cavity of mice were counted, measured, and collected. Gene expression of inflammatory cytokines and estrogen receptor (ER) in the lesions was assessed by real‐time RT‐PCR. Immunohistochemical analysis was used to evaluate the effect of SR on cell proliferation, angiogenic activity, inflammation, and NF‐κB phosphorylation.ResultsTreatment with SR significantly reduced the total number and size of lesions per mouse without inducing endometrial growth. In addition, SR downregulated LPS‐enhanced Vegf, Il‐6, Ptgs‐2, and Ccl‐2 and ER mRNA expression in endometriosis‐like lesions. Immunohistochemical analysis demonstrated a decrease in percentage of positive cells of Ki67, and intensity and rate of positive cells of ERα, CD3, F4/80, PECAM by SR treatment. SR also decreased the expression of NF‐κB p65 and phospho‐NF‐κB p65.ConclusionSR has a regressive effect on the development of murine endometriosis‐like lesions.

01 Dec 2017·Yonago acta medicaQ4 · MEDICINE

SR-16234, a Novel Selective Estrogen Receptor Modulator for Pain Symptoms with Endometriosis: An Open-label Clinical Trial.

Q4 · MEDICINE

Article

Author: Noma, Hisashi ; Ohta, Ikuko ; Taniguchi, Fuminori ; Harada, Tasuku ; Sunada, Hiroshi ; Endo, Yusuke

BackgroundSR-16234 is a selective estrogen receptor modulator (SERM) structurally different from approved SERM and has been reported to have estrogen receptor (ER) α antagonistic activity and strong affinity with a weak partial agonistic activity to ERβ receptor. SR-16234 showed strong inhibitory effects on transplanted endometrial cysts in the endometriosis model of rat and mouse. In this clinical trial, efficacy and safety of SR-16234 have been evaluated in endometriosis patients.MethodsThis trial was an open-label single arm clinical trial. Ten patients with dysmenorrhea and pelvic pain associated with endometriosis and adenomyosis were enrolled in this trial, and received 40 mg of SR-16234 once daily for 12 weeks. The primary endpoint was the visual analogue scale (VAS) of pelvic pain. The secondary endpoints included dysmenorrhea score, pelvic pain score, objective observations (stiffness of Douglas' pouch, limitation of uterine movement, size of ovarian chocolate cysts, thickness of endometrium, and serum CA125 concentration) and safety.ResultsAfter oral administration of SR-16234 40 mg for 12 weeks, there were statistically significant decreases in pelvic pain VAS, total pelvic pain score, total dysmenorrhea score, stiffness of Douglas' pouch, limitation of uterine movement compared with the baseline values.ConclusionThe present trial suggested that a selective estrogen receptor modulator could be used for treatment of pain associated with endometriosis for the first time.

01 Sep 2012·Cancer ScienceQ2 · MEDICINE

Randomized phase II study of three doses of oral TAS‐108 in postmenopausal patients with metastatic breast cancer

Q2 · MEDICINE

ArticleOA

Author: Noguchi, Shinzaburo ; Sato, Nobuaki ; Yamamoto, Naohito ; Tabei, Toshio ; Saeki, Toshiaki ; Saito, Tsuyoshi ; Inaji, Hideo ; Tokuda, Yutaka ; Sato, Yasuyuki ; Nakayama, Takahiro ; Saji, Shigehira ; Kuranami, Masaru ; Takatsuka, Yuichi ; Aogi, Kenjiro ; Yamashita, Hiroko ; Iwata, Hiroji ; Yoshida, Masayuki ; Ikeda, Tadashi ; Kikuchi, Atsushi ; Watanabe, Kenichi

This randomized phase II study was intended to identify the optimal dose of TAS‐108, a novel steroidal antiestrogen, for the treatment of breast cancer in postmenopausal Japanese women. The potential clinical effects of TAS‐108 on the uterus, bone, serum lipids, and hormones were also investigated. Postmenopausal women with hormone receptor‐positive metastatic breast cancer who had previously received one or two endocrine therapies were randomly assigned to one of the three possible dose levels of TAS‐108 (40, 80 or 120 mg/day). Oral TAS‐108 was given daily, and the efficacy and safety of the three doses were evaluated. A total of 97 patients (33, 32, and 32 in the 40‐, 80‐, and 120‐mg groups, respectively) were treated with TAS‐108. The clinical benefit rate was 30.3% for the 40‐mg, 25.0% for the 80‐mg, and 25.0% for the 120‐mg group. The 40‐mg group achieved the prespecified target threshold. TAS‐108 at all dose levels was well tolerated and appeared to have no harmful effects in terms of the variables examined in this study. We conclude that the optimal dose of TAS‐108 among the three doses is 40 mg, once daily, for further studies. JAPIC Clinical Trials Information number: Japic CTI – 121754.

100 Deals associated with SR-16234

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External Link

KEGG	Wiki	ATC	Drug Bank
-	SR-16234	-	DB05966

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Breast cancer recurrent	Phase 2	US	Taiho Pharmaceutical Co., Ltd.	01 May 2004
Breast cancer recurrent	Phase 2	US	SRI International	01 May 2004
Locally advanced breast cancer	Phase 2	US	Taiho Pharmaceutical Co., Ltd.	01 May 2004
Breast Cancer	Phase 2	JP	Taiho Pharmaceutical Co., Ltd.	-
Endometriosis	Phase 2	-	SRI International	-
Endometriosis	Phase 2	-	Taiho Pharmaceutical Co., Ltd.	-
Endometriosis	Phase 2	-	SRI International	-
Endometriosis	Phase 2	JP	Tottori University Hospital	-
Endometriosis	Phase 2	-	Taiho Pharmaceutical Co., Ltd.	-
Endometriosis	Phase 2	JP	Tottori University Hospital	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ASCO2009	Phase 2	Breast Cancer	-	TAS-108 40 mg/day	(astwbslkua) = cgkpjiaitv tvehdtfoce (qpxyollynf ) View more	-	20 May 2009
				TAS-108 80 mg/day	(astwbslkua) = xdpkqqetfl tvehdtfoce (qpxyollynf ) View more