carrimycin / Shenyang Tonglian - LARVOL DELTA

Protease-hydrolysis-driven approach towards the quantification of cellular mRNA after drug treatment in protein nanopores. (PubMed, Anal Chim Acta) - "The proposed nanopore sensor was further performed to assess cellular samples, which showed a ∼4-fold reduction in P2RX7 mRNA levels in the SMMC-7721 cell line pre- and post-carrimycin therapy...This protein nanopore mRNA sensor successfully addressed high molecular weight and complex background species in the quantification of mRNA. Our study introduced an innovative methodology for cellular mRNA quantification to explore the potential therapeutic application of pharmaceuticals, while also offering a new approach for mRNA quantification in disease diagnosis, toxicological assessment, and personalized medicine."

Journal • Oncology

Isovalerylspiramycin I alleviates liver injury and liver fibrosis by targeting the nucleotide-binding protein 2 (NUBP2)-vascular non-inflammatory molecule-1 (VNN1) pathway. (PubMed, J Pharm Anal) - "Simultaneously, the original carrimycin's protective effect on liver damage and fibrosis was verified. Therefore, our study provides potential agents for patients with liver fibrosis-related diseases, and the clear mechanism supports wide application in the clinic."

Journal • Fibrosis • Hepatology • Immunology • Infectious Disease • Liver Cirrhosis • Liver Failure • Respiratory Diseases

The synergistic antitumour effect of Carrimycin combined with 5-fluorouracil on colorectal cancer. (PubMed, Sci Rep) - "In addition, the synergistic effects of the combination therapy were validated in a mouse subcutaneous tumour graft model. In conclusion, CAM enhances the sensitivity of CRC cells to 5-FU both in vitro and in vivo, suggesting its potential as a promising candidate for combination cancer therapy."

Journal • Brain Cancer • CNS Tumor • Colorectal Cancer • Glioblastoma • Hepatocellular Cancer • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Synthesis and evolution of 16-membered macrolide carrimycin derivatives as a novel class of anti-HCoV-OC43 agents targeting viral FSE RNA. (PubMed, Eur J Med Chem) - "Meanwhile, using thermal proteome profiling (TPP) technology, we identified DIS3L2 as a potential host target, which probably assisted 2d to exert the antiviral effect. Therefore, the 16-membered macrolides constituted a new class of RNA inhibitors against coronaviruses, and 2d owns a dual-target mechanism that acts on both viral FSE RNA and host DIS3L2."

Journal • Infectious Disease • Novel Coronavirus Disease

Extensively drug-resistant Acinetobacter baumannii lung abscess and empyema in a patient with fulminant mycoplasma pneumoniae pneumonia. (PubMed, Respir Med Case Rep) - "We present a case involving the concurrence of FMPP and lung abscess and empyema caused by extensively drug-resistant (XDR) A.baumanii. The patient was successfully treated through a novel and effective antibacterial regimen combined with timely drainage."

Journal • Infectious Disease • Pneumonia • Respiratory Diseases

Synthesis, anticancer and antibacterial evaluation of novel spiramycin-acylated derivatives. (PubMed, RSC Adv) - "Spiramycin and its derivatives are commonly used antimicrobials, and its derivative, carrimycin, has recently been found to have good anticancer potential...In particular, compound 16 was the most effective one and comparable to linezolid, a commonly used first-line antimicrobial. These results suggest that spiramycin I derivatives may provide an opportunity to design new anticancer or antibacterial agents, even dual-function agents."

Journal • Oncology

Venetoclax for an ATRA and ATO resistance acute promyelocytic leukemia patient with TNRC18::RARA fusion gene. (PubMed, Leuk Res Rep) - "After treatment with venetoclax, azacitidine, and ATRA, the patient achieved complete remission. The patient also developed pulmonary tuberculosis and a multidrug-resistant infection, which improved considerably after antituberculosis treatment and carrimycin, respectively."

Journal • Acute Promyelocytic Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • Oncology • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Innovative Treatment of Carbapenem-Resistant Pseudomonas aeruginosa Pneumonia with Carrimycin: A Case Report. (PubMed, Ann Clin Lab Sci) - "Initially, we used piperacillin-tazobactam and ceftazidime-avibactam but without satisfactory results. Finally, we administered carrimycin in combination with piperacillin-tazobactam; the patient's condition improved, and he was successfully weaned off the ventilator. Therefore, the combined use of carrimycin should be considered for patients infected with carbapenem-resistant Pseudomonas aeruginosa who do not respond to conventional anti-infection treatments."

Journal • Acute Respiratory Distress Syndrome • Infectious Disease • Pneumonia • Pulmonary Disease • Respiratory Diseases • Septic Shock

Carrimycin, as One of the Drugs in Combination Therapy, for the Treatment of Carbapenem-Resistant Acinetobacter Baumannii Infection. (PubMed, Infect Drug Resist) - "After 3 days of empirical treatment with meropenem, tested positive for A. baumannii infection by the next-generation sequencing, and CRAB was detected in blood and sputum culture. Then, he was administered with tigecycline and amikacin immediately for 5 days, however the therapeutic effect was not significant...The patient received carrimycin monotherapy for 7 days, then discharged. Carrimycin may be a bright alternative for CRAB infection as one of the drugs in combination therapy, especially in a patient with hyperinflammatory response."

Combination therapy • Journal • Cough • Infectious Disease • Inflammation • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases

Carrimycin in a Patient with Acute Myeloid Leukemia Complicated with Life-Threatening Mixed Perianal Infection: A Case Report and Literature Review. (PubMed, Infect Drug Resist) - "Carrimycin is a complementary treatment option when conventional antibiotic therapy fails. It operates through multiple mechanisms beyond its antibiotic properties and warrants further investigation."

Journal • Review • Acute Myelogenous Leukemia • Gastrointestinal Disorder • Hematological Malignancies • Infectious Disease • Leukemia • Oncology • Septic Shock

Carrimycin inhibits coronavirus replication by decreasing the efficiency of programmed -1 ribosomal frameshifting through directly binding to the RNA pseudoknot of viral frameshift-stimulatory element. (PubMed, Acta Pharm Sin B) - "Because the FSE mechanism is essential in all coronaviruses, carrimycin could be a new broad-spectrum antiviral drug for human coronaviruses by directly targeting the conserved coronaviral FSE RNA. This finding may open a new direction in antiviral drug discovery for coronavirus variants."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Efficacy and safety of carrimycin in ten patients with severe pneumonia following solid organ transplantation. (PubMed, World J Clin Cases) - "Carrimycin is a safe and effective treatment modality for SP following solid organ transplantation. Carrimycin may have antibacterial and antiviral effects in patients with SP following solid organ transplantation."

Journal • Acute Respiratory Distress Syndrome • Infectious Disease • Pneumonia • Pulmonary Disease • Respiratory Diseases • Solid Organ Transplantation • Transplantation

Carrimycin ameliorates lipopolysaccharide and cecal ligation and puncture-induced sepsis in mice. (PubMed, Chin J Nat Med) - "Notably, a comparative analysis revealed that CA's anti-inflammatory efficacy surpasses that of equivalent doses of aspirin (ASP) and TIENAM. Collectively, these findings suggest that CA exhibits significant therapeutic potential in sepsis treatment. This discovery provides a foundational theoretical basis for the clinical application of CA in sepsis management."

Journal • Preclinical • Infectious Disease • Inflammation • Oncology • Otorhinolaryngology • Pulmonary Disease • Respiratory Diseases • Septic Shock • Sinusitis • IL1B • IL6 • TNFA

Commentary to "Carrimycin, a first in-class anti-cancer agent, targets selenoprotein H to induce nucleolar oxidative stress and inhibit ribosomal biogenesis"☆. (PubMed, Cancer Pathog Ther) - No abstract available

Journal • Oncology

Effects of carrimycin on biomarkers of inflammation and immune function in tumor patients with sepsis: A multicenter double-blind randomized controlled trial. (PubMed, Pharmacol Res) - "In tumor patients with sepsis, particularly in those experiencing immunological suppression, carrimycin effectively regulates immune responses by increasing HLA-DR and CD8 T cell levels and plays an anti-infective role, reducing disease severity. (Chictr.org.cn, ID Number: ChiCTR2000032339)."

Biomarker • Journal • Infectious Disease • Oncology • Septic Shock • CD4 • CD8 • CRP

Carrimycin, a first in-class anti-cancer agent, targets selenoprotein H to induce nucleolar oxidative stress and inhibit ribosome biogenesis. (PubMed, Cancer Pathog Ther) - "This inhibits ribosomal RNA transcription and subsequent ribosomal assembly, which prevents cancer cells from sustaining elevated rates of protein synthesis and cellular proliferation that are necessary for tumor growth and malignancy. In this review, we (1) describe the historical categorization and evolution of anti-cancer agents, including macrolide antibiotics, (2) outline the discovery of SelH as a target of ISP I, and (3) summarize the ways in which carrimycin has been used both clinically and at the bench to date and propose additional potential therapeutic uses."

Journal • Oncology

Efficacy and Safety of Carrimycin Tablets in HLH Patients With Carbapenem-resistant Infections (clinicaltrials.gov) - P=N/A | N=20 | Not yet recruiting | Sponsor: Beijing Friendship Hospital

New trial • Immunology • Infectious Disease • Rare Diseases

Anti-inflammatory effect and antihepatoma mechanism of carrimycin. (PubMed, World J Gastroenterol) - "We determined that CAM inhibited inflammation. We also predicted the complex multitargeted effects of CAM that involve multiple pathways and the diversity of these effects in the treatment of liver cancer, which provides a basis and direction for further clinical research."

Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Infectious Disease • Liver Cancer • Oncology • Solid Tumor • CASP3 • EGFR • ER • IL1B • IL4

Carrimycin in Patients With Locally Advanced, Recurrent, or Metastatic HNSCC (Non NPC): A Phase I Trial (clinicaltrials.gov) - P1 | N=9 | Completed | Sponsor: Shanghai Jiao Tong University School of Medicine | Active, not recruiting ➔ Completed | Trial primary completion date: Nov 2020 ➔ Dec 2022

Metastases • Trial completion • Trial primary completion date • Head and Neck Cancer • Oncology • Oral Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Study to Evaluate Safety and Efficacy of Carrimycin for Treatment of Severe Coronavirus Disease 2019 (COVID-19) in Hospitalized Patients (clinicaltrials.gov) - P3 | N=93 | Terminated | Sponsor: Shenyang Tonglian Group CO., Ltd | N=300 ➔ 93 | Trial completion date: Nov 2022 ➔ May 2022 | Suspended ➔ Terminated | Trial primary completion date: Nov 2022 ➔ Mar 2022; sponsor strategy change

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Study to Evaluate Safety and Efficacy of Carrimycin for Treatment of Severe Coronavirus Disease 2019 (COVID-19) in Hospitalized Patients (clinicaltrials.gov) - P3 | N=300 | Suspended | Sponsor: Shenyang Tonglian Group CO., Ltd | Recruiting ➔ Suspended

Trial suspension • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Study to Evaluate Safety and Efficacy of Carrimycin for Treatment of Severe Coronavirus Disease 2019 (COVID-19) in Hospitalized Patients (clinicaltrials.gov) - P3 | N=300 | Recruiting | Sponsor: Shenyang Tonglian Group CO., Ltd | Trial completion date: Jul 2022 ➔ Nov 2022 | Trial primary completion date: Jul 2022 ➔ Nov 2022

Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Isovalerylspiramycin I suppresses non-small cell lung carcinoma growth through ROS-mediated inhibition of PI3K/AKT signaling pathway. (PubMed, Int J Biol Sci) - "Some studies have shown that carrimycin, a Chinese Food and Drug Administration (CFDA)-approved macrolide antibiotic, possesses potent anti-tumor effects against oral squamous cell carcinoma...Moreover, we identified ROS accumulation and PI3K/AKT pathway inhibition in tumor xenograft models in vivo as well. Taken together, our study firstly reveals that ISP-I is a novel ROS inducer and may act as a promising candidate with multi-target and low biological toxicity for anti-NSCLC treatment."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Oral Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Targeting selenoprotein H in the nucleolus suppresses tumors and metastases by Isovalerylspiramycin I. (PubMed, J Exp Clin Cancer Res) - "We demonstrated that ISP I links cancer cell vulnerability to oxidative stress and RNA biogenesis by targeting SELH. This suggests a potential new cancer treatment paradigm, in which the primary therapeutic agent has minimal side-effects and hence may be useful for long-term cancer chemoprevention."

Journal • Oncology • MAPK9

Anti-Tumor Effects of Carrimycin and Monomeric Isovalerylspiramycin I on Hepatocellular Carcinoma in Vitro and in Vivo. (PubMed, Front Pharmacol) - "These results show that carrimycin and monomeric isovalerylspiramycin I promoted apoptosis and inhibited proliferation, migration, and invasion of hepatocellular carcinoma cells. Therefore, our discovery suggests anti-tumor capacity for carrimycin and monomeric isovalerylspiramycin I and provides data on potential new drugs for inhibiting hepatocellular carcinoma."

IO biomarker • Journal • Preclinical • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Oncology • Solid Tumor • Transplantation • PD-L1