Delving into the Latest Updates on Flizasertib with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

+ [2]

Target

RIPK1

Action

inhibitors

Mechanism

RIPK1 inhibitors(Receptor-interacting serine/threonine-protein kinase 1 inhibitors)

Therapeutic Areas

Urogenital Diseases

Active Indication

Acute Kidney Injury

Inactive Indication

Acute Graft Versus Host Disease

Originator Organization

Genentech, Inc.

Active Organization

Genentech, Inc.

Inactive Organization-

License Organization-

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC15H14FN3O

InChIKeyLMXPZWQVDDSYHH-RYUDHWBXSA-N

CAS Registry2268739-68-8

The aim of this study is to evaluate the efficacy and safety of GDC-8264 compared with placebo in participants undergoing cardiac surgery who are determined to be at moderate to high risk of developing AKI and subsequent MAKE at 90 days after surgery (MAKE90). The study will be performed in two parts- Part 1 and Part 2.

Start Date17 Jan 2025

Sponsor / Collaborator

Genentech, Inc.

NCT05673876

/ TerminatedPhase 1

A Phase Ib, Open-label, Randomized, Dose-finding, Multicenter Study to Evaluate the Safety, Pharmacokinetics, and Efficacy of GDC-8264 in Combination With Standard of Care in the Treatment of Acute Graft-versus-Host Disease in Patients Who Have Undergone Allogeneic Hematopoietic Stem Cell Transplantation

The primary purpose of the study is to assess the safety and pharmacokinetics (PK) of GDC-8264 in participants with acute graft-versus-host disease (aGVHD).

Start Date06 Apr 2023

Sponsor / Collaborator

Genentech, Inc.

NL-OMON55161

/ CompletedNot Applicable

A PHASE I, RANDOMIZED, DOUBLE BLINDED, PLACEBO CONTROLLED STUDY TO EVALUATE THE SAFETY, TOLERABILITY, AND PHARMACOKINETICS OF SINGLE AND MULTIPLE ASCENDING DOSES OF ORAL GDC-8264 AND THE EFFECT OF FOOD ON THE PHARMACOKINETICS OF GDC-8264 IN HEALTHY VOLUNTEERS - GDC-8264 SAD/MAD/FE Study

Start Date20 Dec 2019

Sponsor / Collaborator

Genentech, Inc.

100 Clinical Results associated with Flizasertib

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100 Translational Medicine associated with Flizasertib

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100 Patents (Medical) associated with Flizasertib

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1

Literatures (Medical) associated with Flizasertib

01 Oct 2023·Clinical and translational science

A phase I, randomized, ascending-dose study to assess safety, pharmacokinetics, and activity of GDC-8264, a RIP1 inhibitor, in healthy volunteers.

Article

Author: Mohanan, Vishnu ; Kshirsagar, Smita ; Ding, Hao ; Rothenberg, Michael E ; Ramakrishnan, Vidya ; Vucic, Domagoj ; Klabunde, Sha ; Di Nucci, Flavia ; Mao, Jialin ; Jones, Nicholas S ; Chen, Yuan ; Pan, Lin ; Ma, Ling ; Lekkerkerker, Annemarie N

Receptor-interacting protein 1 (RIP1) is a key regulator of multiple signaling pathways that mediate inflammatory responses and cell death. RIP1 kinase activity mediates apoptosis and necroptosis induced by tumor necrosis factor (TNF)-α, Toll-like receptors, and ischemic tissue damage. RIP1 has been implicated in several human pathologies and consequently, RIP1 inhibition may represent a therapeutic approach for diseases dependent on RIP1-mediated inflammation and cell death. GDC-8264 is a potent, selective, and reversible small molecule inhibitor of RIP1 kinase activity. This phase I, randomized, placebo-controlled, double-blinded trial examined safety, pharmacokinetics (PKs), and pharmacodynamics (PDs) of single- (5-225 mg) and multiple- (50 and 100 mg once daily, up to 14 days) ascending oral doses of GDC-8264 in healthy volunteers, and also tested the effect of food on the PKs of GDC-8264. All adverse events in GDC-8264-treated subjects in both stages were mild. GDC-8264 exhibited dose-proportional increases in systemic exposure; the mean terminal half-life ranged from 10-13 h, with limited accumulation on multiple dosing (accumulation ratio [AR] ~ 1.4); GDC-8264 had minimal renal excretion at all doses. A high-fat meal had no significant effect on the PKs of GDC-8264. In an ex vivo stimulation assay of whole blood, GDC-8264 rapidly and completely inhibited release of CCL4, a downstream marker of RIP1 pathway activation, indicating a potent pharmacological effect. Based on PK-PD modeling, the GDC-8264 half-maximal inhibitory concentration for the inhibition of CCL4 release was estimated to be 0.58 ng/mL. The favorable safety, PKs, and PDs of GDC-8264 support its further development for treatment of RIP1-driven diseases.

100 Deals associated with Flizasertib

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Acute Kidney Injury	Phase 2	Canada	Genentech, Inc.	17 Jan 2025
Acute Kidney Injury	Phase 2	Belgium	Genentech, Inc.	17 Jan 2025
Acute Kidney Injury	Phase 2	Australia	Genentech, Inc.	17 Jan 2025
Acute Kidney Injury	Phase 2	Spain	Genentech, Inc.	17 Jan 2025
Acute Kidney Injury	Phase 2	United States	Genentech, Inc.	17 Jan 2025
Acute Graft Versus Host Disease	Phase 2	United States	Genentech, Inc.	06 Apr 2023
Acute Graft Versus Host Disease	Phase 2	Canada	Genentech, Inc.	06 Apr 2023

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05673876 (CTgov)	Phase 1	Acute Graft Versus Host Disease	7	GDC-8264 (GDC-8264 35 mg)	hpotujzonc(cedtbxnhbv) = swoqunojeu oewvjohcyk (fbmzzncwel, jxstvwxidv - zorrqimrfv) View more	-	24 Apr 2025
				GDC-8264 (GDC-8264 75 mg)	hpotujzonc(cedtbxnhbv) = mxwvgqwelm oewvjohcyk (fbmzzncwel, txiidcxxtr - tlwiixzloi) View more