COG1410 / Cognosci - LARVOL DELTA

DRUG SCREENING IDENTIFIES BMS-202, COG1410, AND FINGOLIMOD AS BBBPENETRANT COMPOUNDS WITH ANTITUMOR ACTIVITY IN GLIOBLASTOMA CELL LINES (SIOP 2025) - "These findings highlight the therapeutic potential of these drugs for glioblastoma treatment, overcoming traditional barriers and resistance mechanisms. Funding: FAPESP (Grant: 2022/09037-3), INCT BioOncoPed-CNPq (Grant: 406484/2022-8)."

IO biomarker • Preclinical • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • ABCC1 • APOE • NOS1

Modulating Amyloid Pathology-Neural Hyperexcitability Crosstalk for Alzheimer's Disease Therapy. (PubMed, ACS Nano) - "Here, we designed R@AClipo, a nanotherapeutic platform that codelivers the TREM2 agonist peptide COG1410 and the glutamate modulator riluzole via Angiopep-2-modified liposomes capable of crossing the blood-brain barrier. This combinatorial strategy improved cognitive performance and restored neural activity patterns without observable toxicity. Together, these findings support a physiologically compatible strategy that targets the pathological crosstalk between Aβ accumulation and neural hyperexcitability, offering a promising avenue for AD intervention."

Journal • Alzheimer's Disease • CNS Disorders • TREM2

TREM2-mediated neuroinflammatory response is involved in AgNPs-induced ferroptosis in HMC3 cells. (PubMed, Neurotoxicology) - "Treatment with the TREM2 agonist COG 1410 (5μg/mL) significantly upregulated TREM2 expression, attenuated pro-inflammatory factors, and enhanced anti-inflammatory factors. Moreover, TREM2 activation significantly inhibited AgNPs-induced ferroptosis in HMC3 cells, indicating that TREM2-mediated inflammation may play a key role in regulating this process. These findings offer new understanding of AgNPs neurotoxicity and potential therapeutic targets for reducing CNS damage from AgNPs exposure."

Journal • Inflammation • TREM2

COG1410 Alleviated Chronic Sleep Deprivation-Induced Memory Loss by Regulating Microglial Phagocytosis and Inhibiting Hippocampal Inflammation. (PubMed, ACS Chem Neurosci) - "Finally, we downregulated the expression of TREM2 in the hippocampus using small interfering RNA (siRNA), which reduced the protective effect of COG1410 in SD mice. In summary, COG1410 has the potential to prevent SD-induced memory consolidation impairment by maintaining microglial phagocytosis and anti-inflammation in the mouse hippocampus."

Journal • Inflammation • APOE • TREM2

Retraction: Apolipoprotein E-mimetic peptide COG1410 promotes autophagy by phosphorylating GSK-3β in early brain injury following experimental subarachnoid hemorrhage. (PubMed, Front Neurosci) - "[This retracts the article DOI: 10.3389/fnins.2018.00127.]."

Journal • CNS Disorders • Hematological Disorders • Subarachnoid Hemorrhage • Vascular Neurology • APOE • GSK3B

Intranasal Administration of a Novel ApoE-Mimetic Peptide-Coated Gold Nanoparticles as Therapy for Ischemic Stroke. (PubMed, CNS Neurosci Ther) - "CS15-GNPs exhibited favorable neuroprotection and biosafety. This study develops an innovative ApoE-mimetic peptide-capped GNPs, which provides a potential strategy for the treatment of ischemic stroke."

Journal • Cardiovascular • Inflammation • Ischemic stroke • APOE

TREM2 Modulates Postoperative Cognitive Function in Aged Mice by Inhibiting the NLRP3/caspase-1 Pathway and Apoptosis via PLCγ2 Activation. (PubMed, Mol Neurobiol) - "Mice subjected to surgery were pre-treated with the TREM2-activating peptide COG1410, and subsequently evaluated for neuroinflammation, neuronal apoptosis, and cognitive function. TREM2 modulates PLCγ2 activity through SYK phosphorylation, thereby alleviating microglial-driven neuroinflammation and neuronal apoptosis, and improving cognitive impairment following surgery. Targeting the TREM2-PLCγ2 pathway presents a promising strategy for the prevention and treatment of POCD."

Journal • Preclinical • Alzheimer's Disease • Cognitive Disorders • Inflammation • IL18 • IL1B • NLRP3 • PLCG2 • SYK

EXPLORING BLOOD-BRAIN BARRIER-PENETRATING DRUGS FOR THE IDENTIFICATION OF NOVEL THERAPIES IN GLIOBLASTOMA (SIOP 2024) - " Seven drugs: Obatoclax (Mesylate), COG1410, Fingolimod, Ozanimod, Lonafarnib, BMS-202 and Bazedoxifene (acetate) were screened out as potential candidates, with consistent efficacy against glioblastoma cells, providing promising avenues for standalone therapies in GBM or as enhancers of existing conventional chemotherapy regimens. This multi-faceted approach aims to develop personalized and effective treatment strategies for the challenging landscape of glioblastoma tumors. This work was supported by FAPESP grant numbers 2022/09037-3, National Council for Scientific and Technological Development (CNPq, MCTI, Brazil) grant number 406484/2022-8 (INCT BioOncoPed)"

Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

TREM2 alleviates long-term cognitive dysfunction after subarachnoid hemorrhage in mice by attenuating hippocampal neuroinflammation via PI3K/Akt signaling pathway. (PubMed, Brain Res) - "To explore the protective effects of TREM2, we utilized the TREM2 agonist COG1410 to upregulate TREM2 expression and employed TREM2 knockout (KO) mice to verify the necessity of TREM2 for this protective role. In conclusion, TREM2 upregulation mitigates long-term cognitive dysfunction following SAH by attenuating hippocampal neuroinflammation via the PI3K/Akt signaling pathway. These findings suggest that TREM2 could be a potential therapeutic target for improving cognitive outcomes after SAH."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Hematological Disorders • Inflammation • Subarachnoid Hemorrhage • TREM2

TREM2, a critical activator of pyroptosis, mediates the anti‑tumor effects of piceatannol in uveal melanoma cells via caspase 3/GSDME pathwayTREM2, a critical activator of pyroptosis, mediates the anti‑tumor effects of piceatannol in uveal melanoma cells via caspase 3/GSDME pathway. (PubMed, Int J Mol Med) - "As an agonist of TREM2, COG1410‑mediated TREM2 upregulation inhibited proliferation of C918 cells, displaying similar effects to PIC. Furthermore, PIC inhibited tumor growth via regulating the TREM2/caspase 3/GSDME pathway in a mouse model. Collectively, the present study revealed a novel mechanism underlying the inhibitory effects of PIC on UM, providing a potential treatment approach for UM in clinic."

Journal • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma • CASP3 • CASP9 • CAT • GSDMD • GSDME • IL1B • TREM2

Precise Modulation of Pericyte Dysfunction by a Multifunctional Nanoprodrug to Ameliorate Alzheimer's Disease. (PubMed, ACS Nano) - "Inspired by the elevation of vascular cell adhesion molecule-1 (VCAM-1) and reactive oxygen species (ROS) levels in pericyte lesions, we fabricated a multifunctional nanoprodrug by conjugating the hybrid peptide VLC, a fusion of the VCAM-1 high-affinity peptide VHS and the neuroprotective apolipoprotein mimetic peptide COG1410, to curcumin (Cur) through phenylboronic ester bond (VLC@Cur-NPs) to alleviate complex pericyte-related pathological changes. Consequently, VLC@Cur-NPs markedly increased pericyte regeneration to form a positive feedback loop and thus improved neurovascular function and ultimately alleviated memory defects in APP/PS1 transgenic mice. We present a promising therapeutic strategy for AD that can precisely modulate pericytes and has the potential to treat other cerebrovascular diseases."

Journal • Alzheimer's Disease • CNS Disorders • Vascular Neurology • VCAM1

TREM2 alleviates white matter injury after traumatic brain injury in mice might be mediated by regulation of DHCR24/LXR pathway in microglia. (PubMed, Clin Transl Med) - "We demonstrate that TREM2 has the potential to alleviate WMI following TBI, possibly through the DHCR24/LXR pathway in microglia."

Journal • Preclinical • CNS Disorders • Solid Tumor • Vascular Neurology • TREM2

ApoE Mimetic Peptide COG1410 Kills Mycobacterium smegmatis via Directly Interfering ClpC's ATPase Activity. (PubMed, Antibiotics (Basel)) - "This study sheds light on a unique resistance mechanism against AMPs in mycobacteria, highlighting the pivotal role of ClpC in this process. Unraveling the interplay between COG1410 and ClpC enriches our understanding of AMP-bacterial interactions, offering potential insights for developing innovative strategies to combat antibiotic resistance."

Journal • Infectious Disease • APOE

Preclinical Evaluation of Tc-MAG-5-Fab Targeting TREM2 in Lung Cancer Mouse Models: A Comparison with Tc-MAG-5-F(ab'). (PubMed, Mol Pharm) - "Previously, we performed TREM2 targeting imaging by using Ga-NOTA-COG1410 or a I-labeled monoclonal antibody (mAb) and F(ab') in mouse models of colon and gastric tumors. The biodistribution results were consistent with the micro-SPECT/CT imaging results. Tc-MAG-5-Fab could clearly display hTREM2 A549 tumors in a short time (1 h) with low uptake in nontumor organs and tissues and thus has clinical application prospects."

Journal • Preclinical • Gastric Cancer • Gastrointestinal Cancer • Lung Cancer • Oncology • Solid Tumor • TREM2

COG1410 regulates microglial states and protects retinal ganglion cells in retinal ischemia-reperfusion injury. (PubMed, Exp Eye Res) - "The expression of TREM2 showed an increasing trend after COG1410 administration, but it was not statistically significant. In conclusion, COG1410 regulates microglial states and protects RGCs in retinal IR injury, showing promising potential for the treatment of eye diseases."

Journal • Cardiovascular • Glaucoma • Inflammation • Ophthalmology • Reperfusion Injury • APOE • IL1B • MRC1 • NR4A1 • TNFA • TREM2

ApoE Mimic Peptide COG1410 reduces Aβ deposition and improves cognitive function by inducing the transformation of A1/ A2 reactive astrocytes and increasing the BDNF concentration in brain of APP/PS1 double transgenic mice. (PubMed, Neuroscience) - "Administration of COG1410 effectively improved performance in spatial learning and memory of APP/PS1 mice, reduced Aβ deposition and significantly reverted the ratio of A1/A2 reactive astrocytes, which could be associated with BDNF/TrkB signaling pathway. On the whole, the present findings suggest new possibility of using apolipoprotein E mimetic peptide to treat AD with potential effectiveness."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Inflammation • APOE • BDNF

ApoE Mimetic Peptide COG1410 Exhibits Strong Additive Interaction with Antibiotics Against Mycobacterium smegmatis. (PubMed, Infect Drug Resist) - "A time-kill assay showed that COG1410 killed M. smegmatis as potent as clarithromycin, but faster than LL-37, another short synthetic cationic peptide. After 30 passages, there was no induced drug resistance for COG1410. COG1410 was a novel and potent AMP against M. smegmatis by disrupting the integrity of cell membrane."

Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis • APOE

Apolipoprotein E mimetic peptide COG1410 alleviates blood‑brain barrier injury in a rat model of ischemic stroke. (PubMed, Mol Med Rep) - "The mechanism of COG1410 was found to be mediated, as least partly, through the activation of triggering receptor expressed on myeloid cells 2. In conclusion, the data suggest that COG1410 can alleviate BBB injury and neuroinflammation following ischemic stroke."

Journal • Preclinical • Cardiovascular • Immunology • Inflammation • Ischemic stroke • Reperfusion Injury • APOE • CD68 • OCLN

TREM2 activation alleviates neural damage via Akt/CREB/BDNF signalling after traumatic brain injury in mice. (PubMed, J Neuroinflammation) - "Altogether, we are the first to demonstrate that TREM2 activation by COG1410 alleviated neural damage through activation of Akt/CREB/BDNF signalling axis in microglia after CCI. Finally, COG1410 treatment improved neurological behaviour and brain electrophysiological activity after CCI."

IO biomarker • Journal • Preclinical • Cardiovascular • CNS Disorders • Cognitive Disorders • Immunology • Inflammation • Vascular Neurology • BCL2 • CASP3 • IL1B • TNFA • TREM2

Apolipoprotein E mimetic peptide COG1410 combats pandrug-resistant Acinetobacter baumannii. (PubMed, Front Microbiol) - "elegans infection model showed that combined therapy of COG1410 and polymyxin B was capable of significantly rescuing the infected nematodes. Taken together, our study demonstrates that COG1410 is a promising drug candidate in the battle against pandrug-resistant A. baumannii."

Journal • Immune Modulation • Infectious Disease • Inflammation • APOE

Activation of LRP1 Ameliorates Cerebral Ischemia/Reperfusion Injury and Cognitive Decline by Suppressing Neuroinflammation and Oxidative Stress through TXNIP/NLRP3 Signaling Pathway in Mice. (PubMed, Oxid Med Cell Longev) - "Thus, our study suggested that LRP1 activation with COG1410 attenuated cerebral I/R injury at least partially related to modulating microglial polarization through TXNIP/NLRP3 signaling pathway in mice. Thus, COG1410 treatment might serve as a promising therapeutic approach in the management of cerebral I/R patients."

Journal • Preclinical • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Dyslipidemia • Hematological Disorders • Immunology • Inflammation • Reperfusion Injury • Vascular Neurology • APOE • LRP1 • NLRP3 • TXNIP

Synthesis and Evaluation of Ga-NOTA-COG1410 Targeting to TREM2 of TAMs as a Specific PET Probe for Digestive Tumor Diagnosis. (PubMed, Anal Chem) - "The data testified that Ga-NOTA-COG1410 was a specific radioligand targeting TREM2, which could be used to distinguish tumors from inflammation. Using Ga-NOTA-COG1410, the effectiveness of PET on digestive tumors imaging may be enhanced."

Journal • Gastrointestinal Cancer • Gastrointestinal Disorder • Immunology • Inflammation • Oncology

Multifunctional nanorods based on self-assembly of biomimetic apolipoprotein E peptide for the treatment of Alzheimer's disease. (PubMed, J Control Release) - "Besides, the drug delivery system introduces polydopamine (PDA) and COG1410 ligand as a shell to keep the favorable morphology of core and enhance the BBB targeting efficiency. As a result, the delivery system significantly enhances the delivery of MOP to the brain, thus reducing Aβ deposition, mitigating the memory deficits, and ameliorating neurologic damage in AD model mice. Our findings suggest that our drug and carrier integrated multifunctional delivery system has the potential for AD treatment."

Journal • Alzheimer's Disease • CNS Disorders • APOE

TREM2 activation attenuates neuroinflammation and neuronal apoptosis via PI3K/Akt pathway after intracerebral hemorrhage in mice. (PubMed, J Neuroinflammation) - "Our finding demonstrated that TREM2 activation improved neurological functions and attenuated neuroinflammation and neuronal apoptosis after ICH, which was, at least in part, mediated by activation of PI3K/Akt signaling pathway. Therefore, activation of TREM2 may be a potential therapeutic strategy for the management of ICH patients."

IO biomarker • Journal • Preclinical • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Immunology • Inflammation • Ischemic stroke • Vascular Neurology • APOE • BCL2 • IL1B • TNFA

Evaluation of the mimetic peptide APOE COG1410 in the viability, migration, and apoptosis of the intestinal cells IEC-18 after injuries by 5-FU. (PubMed, Ann Oncol) - No abstract available

Journal • APOE