Delving into the Latest Updates on GSK-2879552 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

KDM1A

Mechanism

KDM1A inhibitors(Lysine-specific histone demethylase 1 inhibitors)

Therapeutic Areas

Hemic and Lymphatic DiseasesNeoplasmsRespiratory Diseases

Active Indication-

Inactive Indication

Myelodysplastic SyndromesRefractory acute myeloid leukemiaRelapsing acute myeloid leukemia+ [2]

Originator Organization

GSK Plc

Active Organization

GSK Plc

Inactive Organization-

Drug Highest PhaseDiscovery

First Approval Date-

Regulation-

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Structure

Molecular FormulaC23H28N2O2

InChIKeyLRULVYSBRWUVGR-MMYMAHBISA-N

CAS Registry1401966-63-9

A Phase I/II, Open-label, 2 Arm Study to Investigate the Safety, Clinical Activity, Pharmacokinetics and Pharmacodynamics of GSK2879552 Administered Alone or in Combination With Azacitidine, in Adult Subjects With IPSS-R High and Very High Risk Myelodysplastic Syndromes (MDS) Previously Treated With Hypomethylating Agents (HMA)

This is a Phase I/II, open-label, 2 arm study to evaluate the safety and clinical activity of GSK2879552 alone, or in combination with azacitidine in subjects with MDS. The study consisted of 2 parts. The objective of Part 1 is to determine the recommended phase 2 dose (RP2D) of GSK2879552 administered alone and in combination with azacitidine in adult subjects with high risk MDS previously treated with HMA. The objective of Part 2 is to evaluate clinical activity after treatment with GSK2879552, alone or in combination with azacitidine, in adult subjects with high risk MDS previously treated with HMA.

Start Date31 Jul 2017

Sponsor / Collaborator

GSK Plc

[+1]

EUCTR2016-002294-35-ES / Not yet recruitingPhase 1/2

A phase I/II, open-label, 2 arm study to investigate the safety, clinical activity, pharmacokinetics and pharmacodynamics of GSK2879552 administered alone or in combination with azacitidine, in adult subjects with IPSS-R high and very high risk myelodysplastic syndromes (MDS) previously treated with hypomethylating agents (HMA)

Start Date08 Jun 2017

Sponsor / Collaborator

GlaxoSmithKline Research & Development Ltd.

NCT02177812 / TerminatedPhase 1

A Phase I Open-label, Dose Escalation Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics and Clinical Activity of GSK2879552 Given Orally in Subjects With Relapsed/Refractory Acute Myeloid Leukemia

This study is a phase I, open-label study to determine recommended phase 2 dose (RP2D) and regimen for the orally administered lysine specific demethylase 1 (LSD1) inhibitor GSK2879552, alone or in combination with All-Trans Retinoic Acid (ATRA). The recommended dose and regimen will be selected based on the safety, pharmacokinetic (PK), and pharmacodynamic (PD) profiles observed after the treatment of subjects with relapsed/refractory AML. The study consists of two parts. Part 1 will identify the maximum tolerated dose (MTD) and/or RP2D using a dose-escalation procedure. Dose escalations will be guided by the Neuenschwander-continual reassessment method (N-CRM). PK/PD expansion cohorts will also be included in Part 1 to characterize the range of biologically effective doses by assessing PD markers and obtain additional PK data. Part 2 will explore further the safety, tolerability, and clinical activity of GSK2879552, alone or in combination with ATRA, at the RP2D in subjects with AML.

Start Date27 Aug 2014

Sponsor / Collaborator

GSK Plc

100 Clinical Results associated with GSK-2879552

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100 Translational Medicine associated with GSK-2879552

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100 Patents (Medical) associated with GSK-2879552

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28

Literatures (Medical) associated with GSK-2879552

25 Jan 2024·Journal of Medicinal ChemistryQ1 · MEDICINE

Combination Therapy and Dual-Target Inhibitors Based on LSD1: New Emerging Tools in Cancer Therapy

Q1 · MEDICINE

Review

Author: Hou, Wen-Qing ; Wang, Shu-Wu ; Ji, Shi-Kun ; Liu, Hong-Min ; Wang, Shao-Peng ; Shen, Liang ; Wang, Bo ; Dai, Xing-Jie ; Fu, Meng-Jie

Lysine specific demethylase 1 (LSD1), a transcriptional modulator that represses or activates target gene expression, is overexpressed in many cancer and causes imbalance in the expression of normal gene networks. Over two decades, numerous LSD1 inhibitors have been reported, especially some of which have entered clinical trials, including eight irreversible inhibitors (TCP, ORY-1001, GSK-2879552, INCB059872, IMG-7289, ORY-2001, TAK-418, and LH-1802) and two reversible inhibitors (CC-90011 and SP-2577). Most clinical LSD1 inhibitors demonstrated enhanced efficacy in combination with other agents. LSD1 multitarget inhibitors have also been reported, exampled by clinical dual LSD1/histone deacetylases (HDACs) inhibitors 4SC-202 and JBI-802. Herein, we present a comprehensive overview of the combination of LSD1 inhibitors with various antitumor agents, as well as LSD1 multitarget inhibitors. Additionally, the challenges and future research directionsare also discussed, and we hope this review will provide new insight into the development of LSD1-targeted anticancer agents.

20 Oct 2023·ACS chemical biology

Lysine-Specific Demethylase 1 (LSD1) Inhibitors: Peptides as an Emerging Class of Therapeutics.

Review

Author: Baby, Stephin ; Shinde, Suchita Dattatray ; Sahu, Bichismita ; Kulkarni, Neeraj

Aberrant expression of the epigenetic regulator lysine-specific demethylase 1 (LSD1) has been associated with the incidence of many diseases, particularly cancer, and it has evolved as a promising epigenetic target over the years for treatment. The advent of LSD1 inhibitor-based clinical utility began with tranylcypromine, and it is now considered an inevitable scaffold in the search for other irreversible novel LSD1 inhibitors (IMG-7289 or bomedemstat, ORY1001 or iadademstat, ORY-2001 or vafidemstat, GSK2879552, and INCB059872). Moreover, numerous reversible inhibitors for LSD1 have been reported in the literature, including clinical candidates CC-90011 (pulrodemstat) and SP-2577 (seclidemstat). There is parallel mining for peptide-based LSD1 inhibitors, which exploits the opportunities in the LSD1 substrate binding pocket. This Review highlights the research progress on reversible and irreversible peptide/peptide-derived LSD1 inhibitors. For the first time, we comprehensively organized the peptide-based LSD1 inhibitors from the design strategy. Peptide inhibitors of LSD1 are classified as H3 peptide and SNAIL1 peptide derivatives, along with miscellaneous peptides that include naturally occurring LSD1 inhibitors.

01 May 2023·Bioorganic Chemistry

Recent advances of LSD1/KDM1A inhibitors for disease therapy

Review

Author: Shi, Yuting ; Song, Yihui ; Zhang, Chaofeng ; Yu, Bin ; Wang, Zhiyuan

Lysine-specific demethylase 1 (LSD1/KDM1A) dysregulation is closely associated with the pathological processes of various diseases, especially hematologic malignancies. Significant progresses have been made in the field of LSD1-targeted drug discovery. Nine LSD1 inhibitors including tranylcypromine, ORY-1001, ORY-2001, GSK-2879552, IMG-7289, INCB059872, TAK-418, CC-90011 and SP-2577 have entered clinical stage for disease treatment as either mono- or combinational therapy. This review updates LSD1 inhibitors reported during 2022. Design strategies, structure-activity relationship studies, binding model analysis and modes of action are highlighted. In particular, the unique multiple-copies binding mode of quinazoline derivatives paves new ways for the development of reversible LSD1 inhibitors by blocking the substrate entrance. The design strategy of clinical candidate TAK-418 also provides directions for further optimization of novel irreversible LSD1 inhibitors with low hematological side effects. The influence of the stereochemistry on the potency against LSD1 and its homolog LSD2 is briefly discussed. Finally, the challenges and prospects of LSD1-targeted drug discovery are also given.

100 Deals associated with GSK-2879552

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Myelodysplastic Syndromes	Phase 1	ES	GSK Plc	31 Jul 2017
Myelodysplastic Syndromes	Phase 1	US	GSK Plc	31 Jul 2017
Refractory acute myeloid leukemia	Phase 1	CA	GSK Plc	27 Aug 2014
Refractory acute myeloid leukemia	Phase 1	AU	GSK Plc	27 Aug 2014
Small Cell Carcinoma	Phase 1	ES	GSK Plc	04 Feb 2014
Small Cell Carcinoma	Phase 1	FR	GSK Plc	04 Feb 2014
Small Cell Carcinoma	Phase 1	US	GSK Plc	04 Feb 2014
Small cell lung cancer recurrent	Phase 1	US	GSK Plc	04 Feb 2014
Small cell lung cancer recurrent	Phase 1	ES	GSK Plc	04 Feb 2014
Small cell lung cancer recurrent	Phase 1	FR	GSK Plc	04 Feb 2014

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02034123 (Pubmed) Manual	Phase 1	Small Cell Lung Cancer	29	GSK2879552	(grexdsujrb) = Twelve serious AEs (SAEs) were reported by nine patients, the most common of which was encephalopathy (four SAEs) puxdhdhhcq (pvjxzkbqvv )	Negative	01 Oct 2019
NCT02177812 (CTgov)	Phase 1	Relapsing acute myeloid leukemia \| Refractory acute myeloid leukemia	41	GSK2879552 (Part 1:GSK2879552 1mg QD)	jcqvltyekc(ephizqmmdc) = ftcsjhbrzz dfqjfhjsmz (ehysfeymde, avjwldmvys - dqavazgmjr) View more	-	28 Jun 2019
NCT02177812 (CTgov)	Phase 1		41	GSK2879552 (Part 1: GSK2879552 2mg QD)	jcqvltyekc(ephizqmmdc) = nxpejcgpmj dfqjfhjsmz (ehysfeymde, vdfwevqoje - dadxffnqid) View more	-	28 Jun 2019