MCE | 動物疾病模型介紹 | 引發特定疾病模型 (癌症,神經系統疾病,免疫,發炎) 的化合物產品

MCE | 動物疾病模型介紹 | 引發特定疾病模型 (癌症,神經系統疾病,免疫,發炎) 的化合物產品

2024.08.22

 


MedChemExpress-Master of Small Molecules (Inhibitors. Screening Libraries. Proteins)

Animal models that accurately mimic diseases can be generated through genetic engineering, spontaneous generation, and chemical induction. Ideally, a valuable animal model of any disease should have pathology similar to that of human disease[1].
Compared with genetic engineering and spontaneous models, chemically induced animal disease models are easier to manage and more cost-effective. At present, many chemical-induced disease models have been widely used in the research of tumor,
neurological, endocrine, immune, and other system diseases. These models play important roles in the preclinical research for the development of new drugs.
Cancer Models
Chemical mutagens have the potential to trigger DNA mutations that induce tumor development, and different carcinogens tend to cause mutations at specific locations in the genome[2].
For example, in chemically induced lung tumors,
Kras has been found to mutate more frequently than Hras. N-Nitroso-N-methylurea (MNU) usually causes mutations in Kras codon 12,
whereas Urethane mainly induces mutations in Kras codon 61. Following the initial chemical exposure, metabolism, gene target sequence, DNA repair, tissue type, cell of origin,
and genetic background all factor into the eventual development of a tumor with a distinct set of mutations[2]. Different chemical mutagens can produce tissue-specific or pan-tissue carcinogenesis[3].
Tissue Agent Route
Pan tissue Ionizing radiation
ENU
Whole body exposure
i.p. injection
Skin DMBA
Benzo[a]pyrene
UV
Topical application
Topical application
Topical exposure
Liver N-Nitrosodiethylamine
ENU
Phenobarbital
i.p.injection
i.p.injection
Drinking water
Lung Urethane
NNK
i.p.injection
i.p.injection
Breast DMBA Oral gavage
Colon Azoxymethane
N,N’-Dimethylhydrazine
i.p injection
Table 1. Common Models of Chemical Carcinogenesis[3].
Nervous System Diseases Models
Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the two most common neurodegenerative diseases.
AD is characterized by the deposition of amyloid plaques and neurofibrillary tangles (NFT) in the of cerebral cortex and hippocampus regions of the brain, while PD is caused by the degeneration of dopamine (DA) neurons in the substantia nigra pars compacta (SNpc)[4][5].
Intraventricular administration of Streptozotocin (ICV-STZ), Colchicine, and different fragments of amyloid have been widely used to induce AD models[4].
In humans and non-human primates, MPTP can replicate the motor impairments of PD, including tremors, rigidity, slowness of movement, postural instability, etc[5].
Figure 1. MPTP Biological Validation Results from MedChemExpress.
Immunology and Inflammatory Disease Models
Inflammation constitutes an important part of the body’s immune responses and has five main characteristics: pain, heat, redness, swelling, and loss of function.
Chemical agents, pathogens, and trauma can all recruit inflammatory cells and cytokines, thereby inducing inflammation[6]. For example,
in chemically induced inflammatory bowel disease (IBD) models,
topical administration of hapten agents TNBS or Oxazolone results in T cell-mediated immune responses against haptenized proteins and luminal antigens.
Oral administration of Dextran sulfate sodium salt (DSS) can also cause epithelial cell death, damage barrier function, and cause inflammation[7].
MedChemExpress Products
MedChemExpress (MCE) offers 200+ disease-inducing biochemical products, covering 40+ disease models of cancer, endocrine, immune and inflammation, nervous system, cardiovascular system, respiratory system, digestive system, urinary system, etc., to meet your diverse research needs.
Product Name Description
MPTP hydrochloride A brain penetrant dopamine neurotoxin that can induce Parkinson’s disease model.
PLX5622 A highly selective, brain-penetrant and orally active CSF1R inhibitor that broadly and specifically eliminates microglia.
Streptozotocin An antibiotic widely used in inducing diabetes model.
Tamoxifen An orally active, selective estrogen receptor modulator that can induce gene knockout of CreER transgenic mouse.
N-Nitroso-N-methylurea (MNU) A potent carcinogen that can induce breast and gastric cancer models.
Oxazolone A haptenizing agent that can induce IBD model.
Azoxymethane A carcinogen that can induce colon cancer model.
Doxorubicin hydrochloride A cytotoxic anthracycline antibiotic that can induce nephritis and heart disease models.
References:
[1] Biochem Pharmacol. 2014;87(1):162-171.
[2] Annual Review of Cancer Biology. 2017;1:295-312.
[3] Cold Spring Harb Protoc. 2015;2015(10):865-874.
[4] ACS Omega. 2022;7(51):47504-47517.
[5] Transl Neurodegener. 2023;12(1):36.
[6] Curr Res Immunol. 2023;4:100063.
[7] Nat Protoc. 2017;12(7):1295-1309.

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