Last update 01 Nov 2024

SSTR1

Last update 01 Nov 2024

Basic Info

Synonyms

somatostatin receptor 1, Somatostatin receptor type 1, SRIF-2

+ [5]

Introduction

Receptor for somatostatin with higher affinity for somatostatin-14 than -28. This receptor is coupled via pertussis toxin sensitive G proteins to inhibition of adenylyl cyclase. In addition it stimulates phosphotyrosine phosphatase and Na(+)/H(+) exchanger via pertussis toxin insensitive G proteins.

Drugs associated with SSTR1

Pasireotide Diaspartate

Target

SSTR1 x SSTR2 x SSTR3 x SSTR5

Mechanism

SSTR1 agonists [+3]

Active Org.

Novartis Pharmaceuticals Corp. [+5]

Originator Org.

Novartis Pharma AG

Active Indication

Growth Hormone Excess [+8]

Inactive Indication

Advanced Hepatocellular Carcinoma [+32]

Drug Highest PhaseApproved

First Approval Ctry. / Loc.

EU [+3]

First Approval Date24 Apr 2012

Somatostatin Acetate

Target

SSTR1 x SSTR2 x SSTR3 x SSTR4 x SSTR5

Mechanism

SSTR1 agonists [+4]

Active Org.

Lyomark Pharma GmbH

Originator Org.-

Active Indication

Gastrointestinal Hemorrhage [+1]

Inactive Indication

Peptic Ulcer

Drug Highest PhaseApproved

First Approval Ctry. / Loc.

First Approval Date10 Nov 1997

CAP-232

Target

PKM2 x SSTR1

Mechanism

PKM2 inhibitors [+1]

Active Org.-

Originator Org.

Biostatin Research & Development Ltd.

Active Indication-

Inactive Indication

Kidney Neoplasms [+4]

Drug Highest PhaseDiscontinued

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

146

Clinical Trials associated with SSTR1

NCT06456359 / Not yet recruitingPhase 2IIT

Pasireotide as Maintenance Treatment With Monthly Deep Intramuscular Injection in SSTR2/3/5-Expressing Synovial Sarcoma and Desmoplastic Small Round Cell Tumor

PAMSARC is a non-commercial interventional Phase 2 clinical trial of academic research institutions, with its primary goal being to improve medical treatment of fusion driven Desmoplastic small round cell tumor (DSRCT) and Synovial sarcoma (SySa) in young adults and adolsecents with male predominance.
Current management of DSRCT and SySa includes chemotherapy, radiation and aggressive cytoreductive surgery. Despite advances in multimodal therapy, outcomes remain poor with frequent disease recurrence and very limited options for patients with advanced disease.
Selected somatostatin receptor (SSTR) family members, i.e., SSTR2, SSTR3 and SSTR5, are frequently overexpressed in DSRCT and SySa, providing the rationale for treatment with somatostatin analogues (SSA).
Pasireotide is a SSA with high affinity for SSTR1, -2, -3, and -5 and is approved for the treatment of Cushing's disease and acromegaly and has also shown activity in other cancers. In patients with advanced stage DSRCT and SySa, conventional chemotherapeutic approaches frequently lead to disease response, however, the duration of progression-free time after chemotherapy is short. The targeted approach with pasireotide after initial intensive multimodal treatment may have the potential to significantly improve outcome.

Start Date01 Sep 2024

Sponsor / Collaborator

University Hospital Heidelberg

NL-OMON57054 / SuspendedNot ApplicableIIT

*Managing pasireotide-associated hyperglycaemia in acromegaly with eucaloric very-low carbohydrate ketogenic diet versus diabetes medication: a multicentre, randomized, open-label proof-of-concept study* - PasiAcroKeto

Start Date01 Jul 2024

Sponsor / Collaborator-

CTIS2023-505791-30-01 / Recruiting

A multicentric, randomized, double-blind, placebo-controlled trial to evaluate the efficacy of COLIRIOBCN070660 administered topically in patients with moderately severe to severe non-proliferative diabetic retinopathy - RETISOM

Start Date08 May 2024

Sponsor / Collaborator-

100 Clinical Results associated with SSTR1

100 Translational Medicine associated with SSTR1

0 Patents (Medical) associated with SSTR1

461

Literatures (Medical) associated with SSTR1

08 Oct 2024·Proceedings of the National Academy of Sciences

Selective ligand recognition and activation of somatostatin receptors SSTR1 and SSTR3

Article

Author: He, Xinheng ; Sun, Shuyang ; Xu, H. Eric ; Zhuang, Youwen ; Wang, Yujue ; Xu, Youwei ; Yang, Guizhu ; Fan, Wenjia ; Cheng, Xi ; Wu, Kai ; Zhang, Jie ; Wang, Yue ; Chen, Lan ; Hu, Wen

Somatostatin receptors (SSTRs) exert critical biological functions such as negatively regulating hormone release and cell proliferation, making them popular targets for developing therapeutics to treat endocrine disorders, especially neuroendocrine tumors. Although several panagonists mimicking the endogenous ligand somatostatin are available, the development of more effective and safer somatostatinergic therapies is limited due to a lack of molecular understanding of the ligand recognition and regulation of divergent SSTR subtypes. Here, we report four cryoelectron microscopy structures of G i -coupled SSTR1 and SSTR3 activated by distinct agonists, including the FDA-approved panagonist pasireotide as well as their selective small molecule agonists L-797591 and L-796778. Our structures reveal a conserved recognition pattern of pasireotide in SSTRs attributed to the binding with a conserved extended binding pocket, distinct from SST14, octreotide, and lanreotide. Together with mutagenesis analyses, our structures further reveal the dynamic feature of ligand binding pockets in SSTR1 and SSTR3 to accommodate divergent agonists, the key determinants of ligand selectivity lying across the orthosteric pocket of different SSTR subtypes, as well as the molecular mechanism underlying diversity and conservation of receptor activation. Our work provides a framework for rational design of subtype-selective SSTR ligands and may facilitate drug development efforts targeting SSTRs with improved therapeutic efficacy and reduced side effects.

01 Oct 2024·Journal of Clinical Investigation

Genomic and transcriptomic features of androgen receptor signaling inhibitor resistance in metastatic castration-resistant prostate cancer

Article

Author: Foye, Adam ; Small, Eric J. ; Kneppers, Jeroen ; van der Heijden, Michiel S. ; van der Heijden, Michiel S ; Farsh, Tatyanah ; Small, Eric J ; Bergman, Andries M ; Severson, Tesa ; Moreno Rodriguez, Thaidy ; Zhu, Xiaolin ; Quigley, David A. ; Vis, Daniël ; Lack, Nathan A. ; Lundberg, Arian ; Feng, Felix Y ; Weinstein, Alana S. ; Bergman, Andries M. ; Aggarwal, Rahul R ; Quigley, David A ; Shrestha, Raunak ; Li, Haolong ; Liu, Tianyi ; Aggarwal, Rahul R. ; Sjöström, Martin ; Feng, Felix Y. ; Weinstein, Alana S ; Zhang, Meng ; Mehra, Niven ; Yu, Ivan ; Zwart, Wilbert ; Lack, Nathan A

BACKGROUNDAndrogen receptor signaling inhibitors (ARSIs) have improved outcomes for patients with metastatic castration-resistant prostate cancer (mCRPC), but their clinical benefit is limited by treatment resistance.METHODSTo investigate the mechanisms of ARSI resistance, we analyzed the whole-genome (n = 45) and transcriptome (n = 31) sequencing data generated from paired metastatic biopsies obtained before initiation of first-line ARSI therapy for mCRPC and after radiographic disease progression. We investigated the effects of genetic and pharmacologic modulation of SSTR1 in 22Rv1 cells, a representative mCRPC cell line.RESULTSWe confirmed the predominant role of tumor genetic alterations converging on augmenting androgen receptor (AR) signaling and the increased transcriptional heterogeneity and lineage plasticity during the emergence of ARSI resistance. We further identified amplifications involving a putative enhancer downstream of the AR and transcriptional downregulation of SSTR1, encoding somatostatin receptor 1, in ARSI-resistant tumors. We found that patients with SSTR1-low mCRPC tumors derived less benefit from subsequent ARSI therapy in a retrospective cohort. We showed that SSTR1 was antiproliferative in 22Rv1 cells and that the FDA-approved drug pasireotide suppressed 22Rv1 cell proliferation.CONCLUSIONOur findings expand the knowledge of ARSI resistance and point out actionable next steps, exemplified by potentially targeting SSTR1, to improve patient outcomes.FUNDINGNational Cancer Institute (NCI), NIH; Prostate Cancer Foundation; Conquer Cancer, American Society of Clinical Oncology Foundation; UCSF Benioff Initiative for Prostate Cancer Research; Netherlands Cancer Institute.

01 Sep 2024·Anticancer Research

Expression Analysis of SSTR 1, 2 and 3 in Small-cell Lung Cancer Patients as Targets for Future Peptide Receptor Radionuclide Therapy

Article

Author: Romanov, Elizabeth ; Sagie, Nitzan ; Sheva, Kim ; Meirovitz, Amichay ; Kezerle, Yarden

BACKGROUND/AIMSmall-cell lung cancer (SCLC) is noted for its high proliferative rate, and while treatable, relapse is common. SCLC is known to potentially express somatostatin receptors (SSTRs). Somatostatin possesses antineoplastic activity through cell-cycle arrest and apoptosis, and angiogenesis inhibition. SSTRs, thus, serve as potential anticancer targets for somatostatin analogue therapies. The aim of the study was to determine the expression rate of SSTR subtypes 1, 2 and 3 in SCLC using immunohistochemistry, and potential predictors of such rates.MATERIALS AND METHODSA total of 147 human, SCLC paraffin-embedded tissue microarrays with corresponding patient age, sex, TNM staging, and disease stage were utilized. Immunohistochemical analysis was performed using anti-SSTR 1, 2 and 3 antibodies, each calibrated using healthy human pancreatic islets as positive controls. Array slides were counterstained with hematoxylin and scored based on stain intensity and percentage of stained cells.RESULTSNo SCLC samples expressed SSTR 1, whereas SSTR 2 and 3 were expressed in 29.4% and 4.35% of cases respectively. While females had higher expression levels of SSTR 2/3, and there was a trend of decreased SSTR 2 expression with increased age, results were not statistically significant. No correlation between disease stage and SSTR expression was found. Co-expression of both SSTR2 and 3 occurred in 5.3% of patients.CONCLUSIONImmunohisto-chemistry is an efficient screening tool to reveal optimum SCLC patients for somatostatin analogue therapy. Whilst there currently exist no accepted norm or predictors of SSTR expression levels in SCLC patients, this study contributes insight into the receptors' varied expression.

News (Medical) associated with SSTR1

26 Oct 2022

·www.prnewswire.com

THE PROSTATE CANCER FOUNDATION ANNOUNCES 2022 YOUNG INVESTIGATOR AWARDS TOTALING $7.2 MILLION FOR PROSTATE CANCER RESEARCH

LOS ANGELES, Oct. 26, 2022 /PRNewswire/ -- The Prostate Cancer Foundation (PCF) today announced the Class of 2022 Young Investigator Award recipients totaling $7.2 million in funding for innovative prostate cancer research. PCF Young Investigator Awards are intended to identify a cohort of future research leaders who will keep the field of prostate cancer research vibrant with new ideas and offer career and project support for early career physicians and scientists who are committed to advancing the prostate cancer field. Thirty-four PCF Young Investigator Awards totaling $7.2 million were granted to the promising next generation of cancer researchers. PCF Young Investigator Awards – Class of 2022 2022 Todd Boehly-PCF Young Investigator Award Principal Investigator: Vipul Bhatia, PhD, Fred Hutchinson Cancer Center Mentors: John K. Lee, MD, PhD; Peter Nelson, MD Project Title: Development of Next-Generation STEAP1 Chimeric Antigen Receptor T Cell Therapies to Combat Antigen Escape and T Cell Dysfunction 2022 CRIS Cancer Foundation, Eustace Wolfington and Larry Leeds-PCF Young Investigator Award Principal Investigator: Dimitrios Doultsinos, PhD, University of Oxford Mentors: Claire Fletcher, PhD; Ian Mills, PhD Project Title: Exploring Synthetic Lethality of Targeting miR346-Unfolded Protein Response Dependent DNA Damage Response Mechanisms in Treatment-Resistant Prostate Cancer 2022 Michael & Lori Milken-PCF Young Investigator Award Principal Investigator: Renu Eapen, MBBS, FRACS (Urology), Peter MacCallum Cancer Center Mentors: Michael Hofman, MBBS; Declan Murphy, MC, BCh, BaO, FRCS Urol, FRACS; Paul Neeson, PhD Project Title: The Clinical and Immune Landscape Changes in Response to Upfront Lutetium PSMA Therapy in Patients with High-Risk Localized Prostate Cancer 2022 Foundation Medicine-PCF Young Investigator Award Principal Investigator: Nicolette Fonseca, PhD , University of British Columbia Mentors: Alexander Wyatt, D.Phil; Kim Chi, MD Project Title: Developing a Novel ctDNA-Based Approach to Patient Risk Stratification and Treatment Selection in mCRPC: A Large Population-Based Cohort Study 2022 ZERO, John & Amy Phelan, and Alec & Kelly Gores-PCF VAlor Young Investigator Award Principal Investigator: Jun Gong, MD, Cedars-Sinai Medical Center Mentors: Stephen Freedland, MD; Edwin Posadas, MD Project Title: A Nationwide VA Study on Systemic Treatment Patterns in Black Patients with Metastatic Castration-Resistant Prostate Cancer 2022 Todd Boehly-PCF Young Investigator Award Principal Investigator: Roni Haas, PhD, University of California, Los Angeles Mentor: Paul Boutros, PhD, MBA Project Title: Associating Germline Variants with Prostate Tumour Evolution and Lethality 2022 Ronald & Victoria Simms-PCF Young Investigator Award Principal Investigator: Ashley E. Holly, PhD, MBA, Cleveland Clinic Mentors: Nima Sharifi, MD; Matthew Vander Heiden, MD, PhD Project Title: Elucidating Metabolic Health for Prostate Cancer Patients through Dietary Intervention (DINE Study) 2022 James Coulter-PCF Young Investigator Award Principal Investigator: Tamara Jamaspishvili, MD, PhD, State University of New York Upstate Medical University Mentors: Jeremy Squire, PhD; Alina Basnet, MD Project Title: Single-Center Retrospective Clinical Study of Artificial Intelligence (AI)-Based Protein Assessment of Three Tumor Suppressor Genes ("Triple-TSG") for Improved Risk Stratification and Treatment Management of Advanced Prostate Cancer 2022 Michael & Lori Milken-PCF Young Investigator Award Principal Investigator: Mayuko Kanayama, MD, PhD, Johns Hopkins University Mentors: Jun Luo, PhD; Tamara Lotan, MD; William Isaacs, PhD Project Title: Functional and Treatment Implications of a Rare Germline HOXB13 Variant Affecting Risk of Lethal Prostate Cancer in Patients of African Ancestry 2022 Wild Dunes MGA-PCF Young Investigator Award Principal Investigator: Dong-Woo Kang, PhD, Harvard: Dana-Farber Cancer Institute Mentors: Christina Dieli-Conwright, PhD, MPH; Alicia Morgans, MD, MPH; Timothy Rebbeck, PhD Project Title: Exercise for Tumor Suppressive Impact in Black Patients with Prostate Cancer on Active Surveillance: The RE-MOVE Trial 2022 Henry M. Jackson Foundation for the Advancement of Military Medicine-PCF Young Investigator Award Principal Investigator: Indu Kohaar, PhD, Center for Prostate Disease Research, Uniformed Services University of the Health Sciences; Henry M. Jackson Foundation for the Advancement of Military Medicine Mentors: Gyorgy Petrovics, PhD; William Douglas Figg Sr., PharmD Project Title: Genetic Determinants of Aggressive Prostate Cancer in African American Patients 2022 Tony & Sage Robbins-PCF Young Investigator Award Principal Investigator: Weiping Li, PhD, Columbia University Medical Center Mentors: Michael Shen, PhD; Christopher Barbieri, MD, PhD; Alberto Ciccia, PhD Project Title: Investigating the Role of Androgen Signaling in Promoting Genomic Instability in Prostate Cancer 2022 Ronald & Victoria Simms-PCF Valor Young Investigator Award Principal Investigator: Neil Lin, PhD, University of California, Los Angeles (UCLA) Mentors: Andrew Goldstein, PhD; Matthew Rettig, MD; Isla Garraway, MD, PhD Project Title: Using a Novel 3D Platform to Develop Metabolism-based Prostate Cancer Therapies 2022 Eustace Wolfington-PCF Young Investigator Award Principal Investigator: Jacob Orme, MD, PhD, Mayo Clinic Mentors: Alan Bryce, MD; Sean Park, MD, PhD; Haojie Huang, PhD Project Title: Overcoming NRG-1-Mediated Resistance in CRPC 2022 Robert Kraft, Adam Cohn, and Igor Tulchinsky-PCF Young Investigator Award Principal Investigator: Ryan Park, MD, Harvard: Massachusetts General Hospital Mentors: Nir Hacohen, PhD; Anthony D'Amico, MD, PhD Project Title: Modulating T cell State to Prevent Radiation-Induced Lymphopenia and Enhance Anti-Tumor Immunity 2022 Joel Holsinger-PCF Young Investigator Award Principal Investigator: Sagar Patel, MD, Winship Cancer Institute of Emory University Mentors: Martin Sanda, MD; Ashesh Jani, MD; Arthur Stillman, MD, PhD Project Title: Biomarker-Based Approaches to Understand and Predict Cardiovascular Toxicity from Androgen Deprivation Therapy in Patients with Prostate Cancer 2022 National Cancer Institute-PCF Young Investigator Award Principal Investigator: Michael Rothberg, MD, National Cancer Institute (NCI) Mentors: Peter Pinto, MD; Adam Sowalsky, PhD Project Title: Identifying Tumor Microenvironmental Factors Associated with Oncologic Response to Irreversible Electroporation Focal Therapy for Prostate Cancer 2022 John Black Charitable Foundation-PCF Young Investigator Award Principal Investigator: Ashwin Sachdeva, MBBS, PhD, University of Manchester Mentors: Noel Clarke, ChM; Nicholas James, PhD, MBBS; Gerhardt Attard, PhD, MBBS Project Title: Mitigating Toxicity of Novel AR-Targeted Therapies in Advanced Prostate Cancer 2022 Steve & Andrea Wynn-PCF Young Investigator Award Principal Investigator: David Sanin, PhD, Johns Hopkins University Mentors: Samuel Denmeade, MD; Edward Pearce, PhD Project Title: Expanded Myeloid-Derived Suppressor Cells Underpin Resistance to Bipolar Androgen Therapy in Patients with Advanced Prostate Cancer 2022 Igor Tulchinsky, Robert Taubman and Richard Sandler-PCF VAlor Young Investigator Award Principal Investigator: Martin Schoen, MD, MPH, Saint Louis Veterans Affairs Medical Center Mentors: Kristen Sanfilippo, MD, MPH; Bruce Montgomery, MD; Ruth Etzioni, PhD Project Title: Outcomes of Metastatic Hormone Sensitive Prostate Cancer in Veterans: Facilitating Personalized Medicine 2022 Michael & Tricia Berns-PCF Young Investigator Award Principal Investigator: Laura Sena, MD, PhD , Johns Hopkins University Mentors: Samuel Denmeade, MD; Erika Pearce, PhD Project Title: Understanding Metabolic Differentiation of Prostate Cancer by Bipolar Androgen Therapy 2022 Point Biopharma-PCF VAlor Young Investigator Award Principal Investigator: Marina Sharifi, MD, PhD , University of Wisconsin Mentors: Joshua Lang, MD; Shuang Zhao, MD, MSc; Brett Carver, MD Project Title: Interrogating the Intersection of PSMA and PI3K Pathway Signaling as a Novel Combination Approach in Treatment Resistant Prostate Cancer 2022 Todd Boehly-PCF Young Investigator Award Principal Investigator: Raunak Shrestha, PhD, University of California, San Francisco Mentors: Felix Feng, MD; David Quigley, PhD Project Title: Investigating Chromatin Reprogramming to Overcome Treatment Resistance in Advanced Prostate Cancer 2022 John Tyson-PCF Young Investigator Award Principal Investigator: Bilal A. Siddiqui, MD, The University of Texas MD Anderson Cancer Center Mentors: Christopher Logothethis, MD; Sumit Subudhi, MD, PhD Project Title: Bispecific Immunotherapy Strategies to Overcome the Immunosuppressive Prostate Tumor Microenvironment 2022 Sage & Tony Minella-PCF Young Investigator Award Principal Investigator: Woogwang Sim, PhD, University of California, San Francisco Mentor: Rohit Bose, MD, PhD Project Title: PTEN/P53 Altered Prostate Cancer has Unique Role for Tumor Associated Macrophages upon Apalutamide Resistance 2022 Nelson & Claudia Peltz-PCF Young Investigator Award Principal Investigator: Udit Singhal, MD, University of Michigan Mentors: Todd Morgan, MD; Felix Feng, MD; Daniel Lin, MD Project Title: Leveraging Artificial Intelligence for Optimization of Active Surveillance and Genetic Testing in Patients with Localized Prostate Cancer 2022 John & Daria Barry-PCF VAlor Young Investigator Award Principal Investigator: Alexandra Sokolova, MD, Oregon Health & Science University Mentors: Bruce Montgomery, MD; Heather Cheng, MD, PhD Project Title: Cascade Genetic Testing in Prostate Cancer: Evaluating and Overcoming Barriers 2022 John Black Charitable Foundation-PCF Young Investigator Award Principal Investigator: Vasilis Stavrinides, MD, PhD, University College London Mentors: Mark Emberton, MD; Emek Demir, PhD Project Title: Immune Topology as a Predictor of Prostate Cancer Outcome in Imaging-Based Cohorts 2022 Ms. Lucy Shostak & Dr. Elliot Abramowitz-PCF Young Investigator Award Principal Investigator: William Storck, PhD, University of Michigan Rogel Cancer Center Mentor: Joshi Alumkal, MD Project Title: Development of a Rational Co-Targeting Approach to Block Neuroendocrine Prostate Cancer Cell Survival 2022 CRIS Cancer Foundation and Clay Hamlin-PCF Young Investigator Award Principal Investigator: Alexander Wurzer, PhD, Technical University of Munich Mentor: Matthias Eiber, MD Project Title: Investigating Radiohybrid PSMA-Ligands for Targeted Alpha Therapy, with the Aim to Improve Targeted Alpha Therapy of Metastatic Castration-Resistant Prostate Cancer 2022 Silas Chou-PCF Young Investigator Award Principal Investigator: Lanbo Xiao, PhD , University of Michigan Mentor: Arul Chinnaiyan, MD, PhD Project Title: Targeting SWI/SNF Chromatin Remodeling Complex to Combat Castrate-Resistant Prostate Cancer 2022 John Miller-PCF Young Investigator Award Principal Investigator: Young Yoo, PhD, Northwestern University Mentors: Sarki Abdulkadir, MD, PhD; Navdeep Chandel, PhD Project Title: Targeting Metabolic Adaptation to Treat TP53-mutated Lethal Prostate Cancer 2022 Ms. Lucy Shostak-PCF Young Investigator Award Principal Investigator: Xiaolin Zhu, MD, PhD , University of California, San Francisco Mentors: Felix Feng, MD; Rahul Aggarwal, MD; David Quigley, PhD Project Title: Investigating SSTR1 as a Novel Therapeutic Target for Acquired Resistance to Androgen Receptor Signaling Inhibitors in Advanced Prostate Cancer 2022 William C. & Gina B. Carithers-PCF Young Investigator Award Principal Investigator: Nicholas Zorko, MD, PhD, University of Minnesota / Masonic Cancer Center Mentors: Jeffrey Miller, MD; Emmanuel Antonarakis, MD; Martin Felices, PhD Project Title: Multiplex Engineered CAR iNK Cells Targeting B7-H3 to Treat Metastatic Castration Resistant Prostate Cancers About the Prostate Cancer Foundation The Prostate Cancer Foundation (PCF) is the world's leading philanthropic organization dedicated to funding life-saving prostate cancer research. Founded in 1993 by Mike Milken, PCF has been responsible for raising close to $1 billion in support of cutting-edge research by more than 2,200 research projects at 245 leading cancer centers in 28 countries around the world. Since PCF's inception, and through its efforts, patients around the world are living longer, suffering fewer complications, and enjoying better quality of life. PCF is committed to creating a global public square for prostate cancer, in service to our mission of ending death and suffering from the disease. Learn more at pcf.org. MEDIA CONTACT: Staci L. Vernick Prostate Cancer Foundation [email protected] [email protected] 610-812-6092 SOURCE Prostate Cancer Foundation

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SSTR1

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