CMBL
CMBL (carboxymethylenebutenolidase homolog) is a cytosolic cysteine hydrolase of the dienelactone hydrolase family. It hydrolytically activates several ester-based prodrugs, and is also known by the previous symbol FLJ23617. Browse Assay Genie's current range of CMBL research reagents below, or read on for the biology behind the target.
CMBL is a cysteine hydrolase whose endogenous substrates and physiological function are unknown. What is established is its activity towards ester-based prodrugs: it cleaves the dioxolone ring to yield the active metabolite together with diacetyl and CO2. In this way CMBL converts the prodrugs olmesartan medoxomil and azilsartan medoxomil into olmesartan and azilsartan, two angiotensin receptor blockers. It can also activate the beta-lactam antibiotics faropenem medoxomil and lenampicillin.
The enzyme preferentially cleaves cyclic esters, and it activates medoxomil-ester prodrugs in which the medoxomil moiety is linked to an oxygen atom. CMBL is highly expressed in liver cytosol, and UniProt records its subcellular location as the cytosol. It belongs to the dienelactone hydrolase family, and its activity is assigned to the EC 3.1.1.45 class. Researchers studying the CMBL gene or the CMBL protein often do so in the context of prodrug metabolism.
The HGNC-approved name is carboxymethylenebutenolidase homolog; earlier names included carboxymethylenebutenolidase-like (Pseudomonas), reflecting similarity to a bacterial enzyme, and the alias FLJ23617 is also used. Orthologues are annotated in mouse and rat, both as Cmbl, which supports comparative work on prodrug activation.
CMBL hydrolyses medoxomil-ester prodrugs, releasing active drug metabolites, so it is central to work on how such compounds are converted.
CMBL converts olmesartan medoxomil and azilsartan medoxomil into olmesartan and azilsartan, two angiotensin receptor blockers.
The enzyme can activate the beta-lactam antibiotics faropenem medoxomil and lenampicillin, making it relevant to antibiotic prodrug studies.
CMBL is highly expressed in liver cytosol and preferentially cleaves cyclic esters, making it a subject for hepatic hydrolase characterisation.
CMBL is a cysteine hydrolase whose physiological substrates are unknown. It is best characterised for activating ester-based prodrugs, cleaving the dioxolone ring to release the active metabolite, diacetyl and CO2. Examples include olmesartan medoxomil, azilsartan medoxomil, faropenem medoxomil and lenampicillin.
The full name is carboxymethylenebutenolidase homolog, and FLJ23617 is a previous symbol. Earlier names were carboxymethylenebutenolidase-like (Pseudomonas) and carboxymethylenebutenolidase homolog (Pseudomonas). The enzyme is assigned to EC 3.1.1.45 and the dienelactone hydrolase family.
Yes. Mouse and rat orthologues are both annotated as Cmbl, which allows rodent models to be used alongside human work. Check the datasheet of any product for its validated reactivity before planning cross-species experiments.
Other hydrolases, drug-metabolising enzymes and liver cytosolic proteins studied alongside CMBL.
Gene and protein annotations from HGNC, NCBI Gene and UniProt Q96DG6; product specifications from Assay Genie datasheets.