Raw Materials Oxaliplatin CAS 61825-94-3

Raw Materials Oxaliplatin is a white or white freeze-dried loose block or powder, its molecular formula is C8H14N2O4Pt, its molecular weight is 397.29, and its melting point is 198.5-199.7℃. Oxaliplatin contains hydrophilic amino groups and is slightly soluble in water. Its solubility at 20℃ is 7.9mg/mL. Insoluble in methanol, insoluble in ethanol and acetone. In an aqueous solution, oxalate is hydrolyzed, so contact with an alkaline solution should be avoided. However, the cyclohexyl diamine group with anticancer activity has not changed, so oxaliplatin is a very stable compound. Oxaliplatin can react with sodium chloride to form a precipitate, and the product is unstable and will decompose quickly, so Oxaliplatin cannot be used in combination with normal saline.

What is Oxaliplatin?

Raw Materials Oxaliplatin is a platinum anticancer drug listed after cisplatin and carboplatin. Oxaliplatin blocks its replication and transcription through the cross-linking of platinum atoms with DNA chains, thus producing anticancer activity. Oxaliplatin has a significant inhibitory effect on many kinds of tumor cells, such as intestinal cancer, non-small cell lung cancer, egg cancer, and breast cancer, and has a good additive or synergistic effect with many anti-tumor drugs, such as 5- fluorouracil, paclitaxel, and cyclophosphamide. Oxaliplatin's toxicity to the gastrointestinal tract, liver, kidney, and bone marrow was significantly reduced compared with cisplatin and carboplatin, and it was well tolerated.

It is the third generation platinum anticancer drug, a platinum compound of diaminocyclohexane, that is, the 1,2-diaminocyclohexane group replaces the amino group of cisplatin.

How does Oxaliplatin work?

Like other platinum drugs, Raw Materials Oxaliplatin exerts its cytotoxicity almost by destroying DNA. Oxaliplatin cross-links with DNA through its metabolites in cells, forming a DNA complex, which then stops the replication of tumor cells and leads to cell apoptosis. Oxaliplatin induces the apoptosis of tumor cells by damaging their DNA, inhibiting the synthesis of DNA and RNA, and triggering the immune response of the body.

1. DNA damage oxaliplatin mainly acts on the chromosomal DNA of cancer cells, but its complexity can also be formed in nucleosomes. In cells, oxaliplatin can induce three types of cross-linking.

(1)DNA cross-linking DNA cross-linking means that in base pairing, two G bases form a pair, or a G-A base pair is formed at a lower frequency, rather than a normal G-C pair. At the same time, DNA cross-linking seems to be the main mechanism for inducing DNA damage.

(2)DNA chain diplomacy is considered to be of great significance in the cytotoxicity of cisplatin. DNA linkage seems to be less important in the anticancer mechanism of oxaliplatin.

(3)DNA- protein cross-linking. As for DNA- protein cross-linking, although it can denature enzymes and other important proteins in cells, the current research has not confirmed that it can cause cell death.

2. Inhibition of DNA synthesis Oxaliplatin can inhibit DNA synthesis because it is an inhibitor of thymic acid synthase. Many studies have found that the thymic acid synthase in cells is lower when oxaliplatin is combined with fluorouracil, but the specific mechanism is still unknown.

3. Inhibition of messenger RNA synthesis Oxaliplatin inhibits RNA transcription by three mechanisms:

① Combined with transcription factors. At the beginning of transcription, platinum -DNA complex can act as the binding point of transcription factors, thus preventing the normal binding of transcription factors with promoters.

② Inhibition of RNA polymerase. Cisplatin can form a complex with some polymerases (such as polymerase II), which prevents the enzyme from entering its active site, thus inhibiting its action. Oxaliplatin should also play this role.

③ Participate in the mechanism of nucleosome histone DNA complex. Nucleosome histone DNA complex affects the binding of DNA strands to RNA polymerase, thus preventing its transcription process. Oxaliplatin can enhance the effect of this pathway.

4. Causes the tumor to produce immune death.

In animal tumor models and human experiments, oxaliplatin can lead to the immune death of tumors. After inducing colon cancer in mice, when treated with oxaliplatin, it was found that there were several immune signals on the surface of colon cancer cells before apoptosis. These signals were the product of interferon γ in T cells and could interact with dendritic cell receptor 4. At present, the reason for this phenomenon is that oxaliplatin causes the body's immune system to respond, thus secreting anti-tumor antibodies. Because in the animal model of dendritic cell receptor 4 deletion and colon cancer patients, although oxaliplatin was injected, the above immune signals could not be observed, the disease-free progression period of these patients was shorter and the overall survival rate was lower, the results were statistically significant.

What are the side effects of oxaliplatin?

1. Hematopoietic toxicity:

Oxaliplatin has certain blood toxicity.

When used alone, it may cause the following adverse reactions:

Anemia, leukopenia, granulocytopenia, thrombocytopenia, sometimes up to grade 3 or 4.

When combined with 5- fluorouracil, the hematological toxicity such as neutropenia and thrombocytopenia increases.

2. Gastrointestinal reaction:

About 10% of patients taking oxaliplatin alone developed severe nausea and vomiting, and 4% developed severe diarrhea. When combined with 5- fluorouracil, these side effects increased significantly.

3. Neurotoxic reaction:

Peripheral sensory neuropathy, characterized by peripheral neuritis, can be divided into acute sensory neuropathy and chronic neurotoxicity. 85% ~ 95% of patients will be stimulated and aggravated in cold.

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Note: This compound should be used for research purposes only. These claims have not been evaluated by the Food and Drug Administration. Please consult your doctor and learn about available studies before using them. This product is not intended to diagnose, treat, cure or prevent any disease.

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