Delving into the Latest Updates on PEP07 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms-

Target

Chk1

Mechanism

Chk1 inhibitors(Checkpoint kinase 1 inhibitors)

Therapeutic Areas

NeoplasmsImmune System DiseasesHemic and Lymphatic Diseases

Active Indication

Solid tumorAcute Myeloid LeukemiaAdvanced cancer+ [1]

Inactive Indication-

Originator Organization

PharmaEngine, Inc.

Active Organization

PharmaEngine, Inc.

Inactive Organization-

Drug Highest PhasePhase 1

First Approval Date-

Regulation-

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The goal of this clinical trial is To establish the safety profile and determine the dose-limited toxicity (DLT) of PEP07 monotherapy in patients with advanced or metastatic solid tumors. To determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of PEP07 monotherapy.
Participants will receive PEP07 administered orally once daily (QD) for 2 consecutive days and 5 days off, every week for 4 weeks until disease progression, intolerable toxicity, confirmed pregnancy, death, consent withdrawal, or other anti-cancer treatment is required, or the Sponsor ends the study, whichever occurs first.

Start Date27 Mar 2024

Sponsor / Collaborator

PharmaEngine, Inc.

NCT05659732 / RecruitingPhase 1

A Phase 1b Study of PEP07 (Checkpoint Kinase 1 Inhibitor) in Patients With Advanced Cancer

The goal of this clinical trial is
* To assess the safety and tolerability of PEP07 administered orally as a single dose and at escalating dose levels, and, to determine the dose-limiting toxicity (DLT) of study treatment in patients with Acute Myeloid Leukemia (AML) and Mantle Cell Lymphoma (MCL).
* To determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of PEP07 monotherapy.
Participants will receive PEP07 administered orally once daily (QD) for 2 consecutive days and 5 days off, every week for 4 weeks until disease progression, intolerable toxicity, confirmed pregnancy, death, consent withdrawal, HSCT or other anti-cancer treatment is required, or the Sponsor ends the study, whichever occurs first.

Start Date17 Jul 2023

Sponsor / Collaborator

PharmaEngine, Inc.

100 Clinical Results associated with PEP07

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100 Translational Medicine associated with PEP07

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100 Patents (Medical) associated with PEP07

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5

Literatures (Medical) associated with PEP07

01 Jul 2022·Biomedicine & Pharmacotherapy

Self-derived peptides from the SARS-CoV-2 spike glycoprotein disrupting shaping and stability of the homotrimer unit

Article

Author: Tait-Burkard, Christine ; Kalathiya, Umesh ; Hupp, Ted ; Daniels, Alison ; Padariya, Monikaben

The structural spike (S) protein from the SARS-CoV-2 β-coronavirus is shown to make different pre- and post-fusion conformations within its homotrimer unit. To support the ongoing novel vaccine design and development strategies, we report the structure-based design approach to develop self-derived S peptides. A dataset of crucial regions from the S protein were transformed into linear motifs that could act as the blockers or stabilizers for the S protein homotrimer unit. Among these distinct S peptides, the pep02 (537-QQFGRDIAD-545) and pep07 (821-RDLICAQKFNGLTVLPPLLTDE-842) were found making stable folded binding with the S protein (550-750 and 950-1050 regions). Upon inserting SARS-CoV-2 S variants in the peptide destabilized the complexed S protein structure, resulting an allosteric effect in different functional regions of the protein. Particularly, the molecular dynamics revealed that A544D mutation in the pep02 peptide induced instability for the complexed S protein, whereas the N943K variant from pep09 exhibited an opposite behavior. An increased protein-peptide binding affinity and the stable structural folding were observed in mutated systems, compared to that of the wild type systems. The presence of mutation has induced an "up" active conformation of the spike (RBD) domain, responsible for interacting the host cell receptor. Among the lower affinity peptide datasets (e.g., pep01), the S1 and S2 subunit in the protein formed an "open" conformation, whereas with higher affinity peptides (e.g., pep07) these domains gained a "closed" conformation. These findings propose that our designed self-derived S peptides could replace a single S protein monomer, blocking the homotrimer formation or inducing stability.

07 Nov 2016·Molecular PharmaceuticsQ2 · MEDICINE

Design and Synthesis of New Cell Penetrating Peptides: Diffusion and Distribution Inside the Cornea

Q2 · MEDICINE

Article

Author: Sala, Marina ; Santi, Patrizia ; Padula, Cristina ; Novellino, Ettore ; Campiglia, Pietro ; Ostacolo, Carmine ; Gatti, Rita ; Spensiero, Antonia ; Belletti, Silvana ; Nicoli, Sara ; Scala, Maria Carmina ; Pescina, Silvia

The role of cell penetrating peptides (CPPs) has been challenged in recent years for drug delivery to ocular tissues for the targeting of both anterior and posterior segments. The enhancement of trans-corneal transport for anterior segment targeting is a very important issue possibly leading to important outcomes on efficacy and to the opportunity of topical administration of molecules with unfavorable penetration properties. The aim of the present work was the design and synthesis of new CPPs, deriving from the structure of PEP-1 peptide. Synthesized peptides were labeled with 5-carboxyfluorescein (5-FAM), and their diffusion behavior and distribution inside the cornea were evaluated by a validated ex vivo model and a confocal microscopy approach. Newly synthesized peptides showed similar corneal permeation profiles as PEP-1 (P_app = 0.75 ± 0.56 × 10^-6 cm/s), about 2.6-fold higher than 5-FAM (P_app = 0.29 ± 0.08 × 10^-6 cm/s) despite the higher molecular weight. Confocal microscopy experiments highlighted the tendency of PEP-1 and its derived peptides to localize in the intercellular space and/or in the plasma membrane. Noteworthy, using penetratin as positive control, a higher trans-corneal permeation (P_app = 6.18 ± 1.46 × 10^-6 cm/s) was evidenced together with a diffusion by intracellular route and a different accumulation between wings and basal epithelial cells, probably depending on the stage of cell development. Finally, PEP-1 and pep-7 proved to be safe and well tolerated when tested on human conjuctival cell line.

01 Sep 2015·Archives of MicrobiologyQ4 · BIOLOGY

Novel antimicrobial peptide specifically active against Porphyromonas gingivalis

Q4 · BIOLOGY

Article

Author: T Nakpheng ; T Suwandecha ; T Srichana ; K Pangsomboon ; N Balekar

Porphyromonas gingivalis, the major etiologic agent of chronic periodontitis, produces a broad spectrum of virulence factors, including outer membrane vesicles, lipopolysaccharides, hemolysins and proteinases. Antimicrobial peptides (AMPs) including bacteriocins have been found to inhibit the growth of P. gingivalis; however, these peptides are relatively large molecules. Hence, it is difficult to synthesize them by a scale-up production. Therefore, this study aimed to synthesize a shorter AMP that was still active against P. gingivalis. A peptide that contained three cationic amino acids (Arg, His and Lys), two anionic amino acids (Glu and Asp), hydrophobic amino acids residues (Leu, Ile, Val, Ala and Pro) and hydrophilic residues (Ser and Gly) was obtained and named Pep-7. Its bioactivity and stability were tested after various treatments. The mechanism of action of Pep-7 and its toxicity to human red blood cells were investigated. The Pep-7 inhibited two pathogenic P. gingivalis ATCC 33277 and P. gingivalis ATCC 53978 (wp50) strains at a minimum bactericidal concentration (MBC) of 1.7 µM, but was ineffective against other oral microorganisms (P. intermedia, Tannerella forsythensis, Streptococcus salivarius and Streptococcus sanguinis). From transmission electron microscopy studies, Pep-7 caused pore formation at the poles of the cytoplasmic membranes of P. gingivalis. A concentration of Pep-7 at four times that of its MBC induced some hemolysis but only at 0.3%. The Pep-7 was heat stable under pressure (autoclave at 110 and 121 °C) and possessed activity over a pH range of 6.8-8.5. It was not toxic to periodontal cells over a range of 70.8-4.4 μM and did not induce toxic pro-inflammatory cytokines. The Pep-7 showed selective activity against Porphyromonas sp. by altering the permeability barriers of P. gingivalis. The Pep-7 was not mutagenic in vitro. This work highlighted the potential for the use of this synthetic Pep-7 against P. gingivalis.

100 Deals associated with PEP07

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Solid tumor	Phase 1	TW	PharmaEngine, Inc.	27 Mar 2024
Acute Myeloid Leukemia	Phase 1	AU	PharmaEngine, Inc.	17 Jul 2023
Acute Myeloid Leukemia	Phase 1	TW	PharmaEngine, Inc.	17 Jul 2023
Advanced cancer	Phase 1	AU	PharmaEngine, Inc.	17 Jul 2023
Advanced cancer	Phase 1	TW	PharmaEngine, Inc.	17 Jul 2023
Mantle-Cell Lymphoma	Phase 1	TW	PharmaEngine, Inc.	17 Jul 2023
Mantle-Cell Lymphoma	Phase 1	AU	PharmaEngine, Inc.	17 Jul 2023