K-604 / Kowa - LARVOL DELTA

Herpes simplex virus 1 infection induces ubiquitination of UBE1a. (PubMed, Biochem J) - "Furthermore, we found that UBE1a and ubiquitination at K604 in UBE1a retarded expression of HSV-1 major capsid protein, ICP5. Our findings show that UBE1a functions as an antiviral factor that becomes activated upon ubiquitination at Lys604."

Journal • CNS Disorders • Herpes Simplex • Infectious Disease • Keratitis • Ocular Inflammation • Ophthalmology • Targeted Protein Degradation

Microginins from a Microcystis sp. Bloom Material Collected from the Kishon Reservoir, Israel. (PubMed, Mar Drugs) - "...Ten microginins, microginins KR767 (1), KR801(2), KR835 (3), KR785 (4), KR604 (5), KR638 (6), KR781 (7), KR815 (8), FR3 (9), and FR4 (10), were isolated from the extract of a bloom material of Microcystis sp...These microginins differ in sequence and absolute configuration of the chiral centers of the Ahda moieties and by-methylation of the Ahda amine group and extent of chlorination of the Ahda terminal methyl group. The compounds were evaluated for inhibition of the zinc metalloprotease, aminopeptidase M, and exhibited low- to sub-nanomolar half maximal inhibitory concentration (IC) values."

Journal • Biosimilar

"KN604 seems no different. OS lack of significance seems something of a statistical aberration. #LCSM" (@DrRiyazShah)

Lung Cancer • Oncology

Syntheses and pharmacokinetic evaluations of four metabolites of 2-(4-(2-((1H-benzo[d]imidazol-2-yl)thio)ethyl)piperazin-1-yl)-N-(6-methyl-2,4-bis-(methylthio)pyridin-3-yl)acetamide hydrochloride [K-604], an acyl-CoA:cholesterol O-acyltransferase-1 inhibitor. (PubMed, Bioorg Med Chem) - "We orally administered a single dose of 10 mg/kg of 1 to monkeys because the in vitro metabolic patterns are quite similar. Fortunately, the drug concentration of 1 was much higher than those of M1, M2, M3 and M4."

Journal • PK/PD data

"KN604 PFS significant; OS not. https://t.co/p02HdDF3JQ #LCSM" (@DrRiyazShah)

Brain Targeting of Acyl-CoA:Cholesterol O-Acyltransferase-1 Inhibitor K-604 via the Intranasal Route Using a Hydroxycarboxylic Acid Solution. (PubMed, ACS Omega) - "Even with intranasal administration of K-604 once per day for 7 days, the level of cholesteryl esters markedly decreased from 0.70 to 0.04 μmol/g in the mouse brain. Thus, this application will be a crucial therapeutic solution for ACAT-1 overexpressing diseases in the brain."

Journal

Discovery of the Clinical Candidate 2-(4-(2-((1 H-benzo[ d]imidazol-2-yl)thio)ethyl)piperazin-1-yl)- N-(6-methyl-2,4-bis(methylthio)pyridin-3-yl)acetamide hydrocholoride [K-604], an Aqueous Soluble Acyl-CoA: Cholesterol O-Acyltransferase (ACAT/SOAT)-1 Inhibitor. (PubMed, J Med Chem) - "After ensuring the pharmacological effects and safety, we designated 2 as a clinical candidate, named K-604. Considering the therapeutic results of ACAT inhibitor in past clinical trials, we believe that K-604 will be useful for the treatment of incurable diseases involving ACAT-1 overexpression."

Clinical • Journal

Characterization of an endonuclease in rice stripe tenuivirus Pc1in vitro. (PubMed, Virus Res) - "Mutations in the endonuclease domain allowed the identification of four key residues (D547, D567, E585 and K604). The endonuclease of RSV was similar but not identical to other known viral endonucleases, suggesting that RSV endonuclease may have some distinct catalytic characteristics."

Journal • Preclinical