Last update 01 Nov 2024

GR x 11β-HSD1

Last update 01 Nov 2024

Basic Info

Related Targets

GR11β-HSD1

Drugs associated with GR x 11β-HSD1

SPI-62/prednisolone

Target

11β-HSD1 x GR

Mechanism

11β-HSD1 inhibitors [+1]

Active Org.

Sparrow Pharmaceuticals, Inc.

Originator Org.

Sparrow Pharmaceuticals, Inc.

Active Indication

Polymyalgia Rheumatica

Inactive Indication-

Drug Highest PhasePhase 2

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with GR x 11β-HSD1

NCT05436652 / RecruitingPhase 2

A Trial of Prednisolone in Combination With SPI-62 or Placebo in Subjects With Polymyalgia Rheumatica (PMR)

This will be a single-blind, placebo-controlled phase 2 trial to compare prednisolone effects with and without SPI-62 in participants with PMR.

Start Date22 Jul 2022

Sponsor / Collaborator

Sparrow Pharmaceuticals, Inc.

100 Clinical Results associated with GR x 11β-HSD1

100 Translational Medicine associated with GR x 11β-HSD1

0 Patents (Medical) associated with GR x 11β-HSD1

313

Literatures (Medical) associated with GR x 11β-HSD1

01 Sep 2024·Reproduction in Domestic Animals

Local Regulatory Changes of HSD11B1 and NR3C1 in the Follicular and Luteal Tissue During Experimentally Induced Ovulation in the Cow

Article

Author: Berisha, Bajram ; Thaqi, Granit ; Pfaffl, Michael W.

ABSTRACTThe objective of the study was to characterise the expression patterns of the two key components of cortisol action namely HSD11B1 (11‐beta‐hydroxysteroid dehydrogenase type 1) and NR3C1 (nuclear receptor subfamily 3, group C, member 1, also known as the glucocorticoid receptor) in superovulation induced bovine follicles during the periovulation and subsequent corpus luteum (CL) formation. Bovine ovaries containing preovulatory follicles or CL were timely defined during induced ovulation as follows: 0 h before GnRH (Gonadotropin‐releasing hormone) application, and 4, 10, 20, 25 (follicles) and 60 h (early CL) after GnRH. The low mRNA expression of HSD11B1 and NR3C1 in the follicle group before the GnRH application increased significantly in the follicle group 20 h after GnRH and remained high afterward also in the early CL group. In contrast, the high NR3C1 mRNA decreased in follicles 25 h after GnRH (close to ovulation) and significantly increased again after ovulation (early CL). Our results indicated the involvement of HSD11B1 and NR3C1 as the two key components of cortisol action in the local mechanisms coordinating final follicle maturation, ovulation, follicular‐luteal transition and CL development in the cow.

30 Aug 2024·Rapid Communications in Mass Spectrometry

Integrated multicomponent analysis based on ultra‐high‐performance liquid chromatography coupled with quadrupole‐Exactive Orbitrap mass spectrometry and network pharmacology to elucidate the effective constituents and potential mechanism of Zhibai Dihuang pill in treating childhood precocious puberty

Article

Author: Zhang, Zhifeng ; Zhang, Jianguang ; Wulu, Jiansang ; Yang, Qing

RationaleChildhood precocious puberty (CPP) is a common pediatric endocrine disorder with significant associated risks. Zhibai Dihuang pill (ZBDHP), a classic recipe of the Qing dynasty with its efficacy of nourishing yin and clearing heat, can downregulate the expression of ESR1 in the uterus and ovaries, thereby inhibiting CPP. However, as of now, the main active ingredients and pharmacological mechanisms of ZBDHP remain unclear.MethodsA comprehensive approach was proposed using ultra‐high‐performance liquid chromatography coupled with quadrupole‐Exactive Orbitrap mass spectrometry (UHPLC‐Q‐Exactive Orbitrap‐MS) and network pharmacology to explore the potentially active constituents of ZBDHP and reveal the underlying mechanisms against CPP. Molecular docking was used to verify the possible mechanisms.ResultsA total of 214 constituents derived were identified via UHPLC‐Q‐Exactive Orbitrap‐MS, and 12 of them were definitely characterized using reference standards. Subsequently, compounds tetrahydropalmatine, alisol C, 25‐anhydroalisol A 11‐acetate, hispidone, cavidine, alisol E, melianone, neogitogenin, denudatin B, and 16β‐hydroperoxyalisol B with related targets PIK3CA, HSD11B1, CYP19A1, AR, PTGS2, CDK2, NR3C1, MMP2, MMP1, and MAPK1 were regarded as key components and targets for ZBDHP treating CPP using the compound–target–pathway network. Besides, the results revealed that the pathways conduced obviously to therapeutic efficacy, including pathways in cancer, neuroactive ligand–receptor interaction, and cyclic adenosine monophosphate（cAMP） signaling pathways. Molecular docking indicated that PIK3CA, HSD11B1, and CYP19A1 exhibited high affinities to corresponding compounds. Overall, the study determined the multicomponent, multitarget, and multipathway mechanisms of ZBDHP against CPP.ConclusionsThis study provided a new method for exploring the chemical constituents and pharmacology mechanism of traditional Chinese medicine.

14 Aug 2024·JCEM Case Reports

Impaired 11β-HSD1 Activity in a Male Patient With Cushing Disease Resulting in Lack of the Full Cushingoid Phenotype

Article

Author: Liu, Chienying ; Weber, Robert J ; Kawaja, Christopher ; Wallerstein, Robert ; Kunwar, Sandeep M

AbstractWe present a patient who had surgically confirmed CD but without the full cushingoid phenotype despite markedly elevated cortisol. Nonpathologic causes of elevated ACTH and cortisol were eliminated as were pathogenic variants in the glucocorticoid receptor gene. Further studies of urine metabolites, cortisol half-life, and the ratios of cortisone to cortisol conversion revealed impaired 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) activity. There have only been 2 prior reports of impaired 11β-HSD1 resulting in lack of classic cushingoid features in the past 2 decades. Our patient's presentation and previous reports demonstrate the key role of 11β-HSD1 in modulating intracellular cortisol concentration, therefore shielding the peripheral tissues from the effects of excess cortisol. When patients present with markedly elevated cortisol but without classic cushingoid features, impaired 11β-HSD1 should be considered in the differential diagnosis.

Analysis

Perform a panoramic analysis of this field.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis