MIA-602 / University of Miami - LARVOL DELTA

Growth Hormone-Releasing Hormone (GHRH) Antagonist Peptides Combined with PI3K Isoform Inhibitors Enhance Cell Death in Prostate Cancer. (PubMed, Cancers (Basel)) - "The ability of the MIA-602/690 + PI3K inhibitor combination to alter multiple signaling pathways may weaken the activation of adaptive mechanisms resulting from each drug and improve efficacy."

Journal • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • AR • CCNA2 • E2F1 • PIK3CA • PIK3CB • PTEN

Alveolar Epithelial GHRH Receptor Interacts With TLR4 and GRK4 to Facilitate Inflammation (ATS 2025) - "Inhibition of GHRH-R using an antagonist, MIA-602, reduces lung inflammation and fibrosis due to bleomycin in a murine model. These studies provide foundational support for our observation that GRK4 can facilitate the inhibitory effects of GHRH-R antagonist, MIA-602, on inflammation mediated by AT2 cells through TLR-4. Such results indicate that anti-inflammatory actions of MIA-602 may be mediated by inhibition of the TLR4, which limits expression of the inflammatory phenotype in alveolar epithelial cells."

IO biomarker • Acute Lung Injury • Fibrosis • Infectious Disease • Inflammation • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases • MYD88 • TLR4

Growth Hormone-Releasing Hormone Antagonists Increase Radiosensitivity in Non-Small Cell Lung Cancer Cells. (PubMed, Int J Mol Sci) - "Finally, both MIA-602 and MIA-690 enhanced radiosensitivity in primary human NSCLC cells. These findings highlight the potential of GHRH antagonists as radiosensitizers in NSCLC treatment."

IO biomarker • Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BCL2 • CASP3 • CDH1 • IGF1

A novel approach for the treatment of AML, through GHRH antagonism: MIA-602. (PubMed, Rev Endocr Metab Disord) - "GHRH-Ant act in manners that are orthogonal to anthracyclines and when administered in combination synergize to produce a more potent anti-neoplastic effect. Considering the adversities associated with standard AML therapies and the developing issue of drug resistance, MIA-602 represents a novel approach worth further investigation."

Journal • Review • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Palliative care • Transplantation

Growth Hormone Releasing Hormone Receptor (GHRH-R) Mediates Alveolar Epithelial Type 2 Cell Inflammation (ATS 2024) - "GHRH-R antagonist MIA-602 inhibits pro-inflammatory cytokine gene expression by AT2 cells, implicating GHRH-R signaling as a mechanism of lung inflammation...Both GHRH peptide and LPS similarly trigger activation of JAK2/STAT3 and NF-κB, which further promote an iAT2 cell inflammatory phenotype facilitating lung injury. The ability to modulate GHRH-R activation provides a potential therapeutic approach to ALI that could remediate both inflammation and subsequent fibrosis."

Acute Lung Injury • Fibrosis • Infectious Disease • Inflammation • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases • ICAM1 • IL1B • TLR4 • TNFA

Exploring the role of GHRH antagonist MIA-602 in overcoming doxorubicin resistance in acute myeloid leukemia (AACR 2024) - "This is of particular interest for those who are resistant to conventional chemotherapy, further broadening the spectrum of treatment options available. Additional investigations are warranted to progress these findings to in vivo xenograft models."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Exploring the role of GHRH antagonist MIA-602 in overcoming Doxorubicin-resistance in acute myeloid leukemia. (PubMed, Oncotarget) - "Our in vivo experiment of xenografted nude mice with Doxorubicin-resistant K-562 revealed a reduction in tumor volume with MIA-602 treatment compared to control. Our study demonstrates that these three AML cell lines, and their Doxorubicin-resistant clones, are susceptible to GHRH antagonist MIA-602."

Journal • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Transplantation

Effects of GHRH Deficiency and GHRH Antagonism on Emotional Disorders in Mice. (PubMed, Cells) - "Finally, we also found significantly decreased COX-2, iNOS, NFkB, and TNF-α gene expressions, as well as increased P-AKT and AKT levels in +/+ MIA-602 and -/- control animals compared to +/+ mice treated with vehicle (+/+ control). We hypothesize that the generalized ablation of the GHRH gene leads to a dysregulation of neural pathways, which is mimicked by GHRH antagonist treatment."

Journal • Preclinical • CNS Disorders • Depression • Growth Hormone Deficiency • Mood Disorders • Psychiatry • NQO1 • TNFA

Growth hormone-releasing hormone receptor antagonist MIA-602 attenuates cardiopulmonary injury induced by BSL-2 rVSV-SARS-CoV-2 in hACE2 mice. (PubMed, Proc Natl Acad Sci U S A) - "GHRH-R antagonist, MIA-602, has been reported to modulate immune responses to bleomycin lung injury and inflammation in granulomatous sarcoidosis. MIA-602 rescued altered respiratory rate, increased expiratory parameters (Te, PEF, EEP), and normalized airflow parameters (Penh and Rpef) compared to vehicle, consistent with decreased airway inflammation. RNASeq followed by protein analysis revealed heightened levels of inflammation and end-stage necroptosis markers, including ZBP1 and pMLKL induced by rVSV-SARS-CoV-2, that were normalized by MIA-602 treatment, consistent with an anti-inflammatory and pro-survival mechanism of action in this preclinical model of COVID-19 pneumonia."

Journal • Preclinical • Acute Lung Injury • Acute Respiratory Distress Syndrome • Immunology • Infectious Disease • Inflammation • Novel Coronavirus Disease • Pneumonia • Pulmonary Disease • Respiratory Diseases • Sarcoidosis • ICAM1 • IGF2BP1

Growth hormone-releasing hormone antagonist MIA-602 inhibits inflammation induced by SARS-CoV-2 spike protein and bacterial lipopolysaccharide synergism in macrophages and human peripheral blood mononuclear cells. (PubMed, Front Immunol) - "Finally, MIA-602 prevented the effect of S protein and LPS synergism on NF-кB nuclear translocation and activity. Overall, these findings demonstrate a novel antinflammatory role for GHRH antagonists of MIA class and suggest their potential development for the treatment of inflammatory diseases, such as COVID-19 and related comorbidities."

Journal • Acute Respiratory Distress Syndrome • Infectious Disease • Inflammation • Novel Coronavirus Disease • Oncology • Pulmonary Disease • Respiratory Diseases • CXCL8 • IL1B • MMP9 • STAT3 • TNFA

Alveolar epithelial cell growth hormone releasing hormone receptor in alveolar epithelial inflammation. (PubMed, Exp Lung Res) - "Exposure to LPS or cytokines increased iAT2 cell production of pro-inflammatory factors. GHRH-R antagonist MIA-602 inhibited pro-inflammatory gene expression, implicating iAT2 cell GHRH-R signaling in lung inflammation and potentially in fibrosis."

Journal • Fibrosis • Immunology • Inflammation • Pneumonia • ACTA2 • CDH2 • COL1A1 • FN1 • TGFB1 • TNFA • VIM

The Application of GHRH Antagonist as a Treatment for Resistant APL. (PubMed, Cancers (Basel)) - "Additionally, combination therapy with both doxorubicin (DOX) and MIA-602 showed a marked synergistic effect in reducing the proliferation of the K-562 AML cell line. These findings suggest that MIA-602 could be utilized to address resistance to all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) therapies, as well as in augmenting anthracycline-based regimens."

Journal • Acute Myelogenous Leukemia • Oncology

Alveolar Type 2 Cell Growth Hormone Releasing Hormone Receptor (GHRH-R) Modulates Inflammatory and Fibrotic Signaling (ATS 2023) - "Inhibition of epithelial GHRH-R with MIA-602, a synthetic GHRH-R antagonist with anti-inflammatory properties, largely prevented increases in gene expression due to cytokines...GHRH-R interacts with the pro-inflammatory NFkB and pro-fibrotic Wnt/B-catenin pathways at the level of JAK/STAT, indicating that iAT2 cells could amplify both inflammation and proliferation of connective tissue. These pathways appear to allow alveolar epithelial cells to participate actively in inflammatory and fibrotic responses."

Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Inflammation • Pneumonia • Respiratory Diseases • ACTA2 • BIRC3 • CCND2 • COL1A1 • CTGF • CXCL8 • ICAM1 • IFNG • IL13 • IL1B • IL33 • IL4 • IRF1 • KRT17 • KRT19 • MMP7 • SOCS3 • TNFA • TSLP

Growth Hormone-releasing Hormone Receptor Antagonist MIA-602 Reduces Chimeric SARS-CoV-2-induced Cardiopulmonary Inflammation in K18-hACE2tg Mice (ATS 2023) - "GHRH-R antagonist, MIA-602, modulates the cellular immune response to bleomycin lung injury (Zhang C, et al. MIA-602 inhibits the GHRH-R and has significant anti-inflammatory effects in a mouse model of COVID-19 infection. Further studies are required to validate its effects on the cardiac and pulmonary function and to elucidate the basic mechanisms of these effects."

Preclinical • Acute Respiratory Distress Syndrome • Cardiovascular • Fibrosis • Immunology • Infectious Disease • Inflammation • Novel Coronavirus Disease • Pneumonia • Pulmonary Disease • Respiratory Diseases • ICAM1 • IGF1 • TERC

Synergistic effects of MIA-602 and its potential for use in ATRA/ATO Resistant APL (AACR 2023) - "Incubation of cells with doxorubicin showed a decrease in proliferation in a dose-dependent manner. Co-incubation of K562 cells with MIA-602 and doxorubicin showed a significantly greater reduction in proliferation (p<0.05). Co-administration of doxorubicin and MIA-602 was shown to have a synergistic effect, when compared to doxorubicin alone at all concentrations at 24 and 48h."

Acute Myelogenous Leukemia • Acute Promyelocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • NCAM1