139504-50-0 Usage
Description
N2'-deacetyl-N2'-(3-Mercapto-1-oxopropyl)-Maytansine, also known as Mertansine (DM1), is a modified form of the natural alkaloid Maytansine. It is an organic heterotetracyclic compound and 19-membered macrocyclic lactam derived from Maytansine, with a sulfanylmethyl group replacing one of the hydrogens of the terminal N-acetyl group. Mertansine acts as a potent antineoplastic agent and a tubulin modulator, inhibiting the dynamicity of microtubules and suppressing the formation of spindles during cell mitosis. This leads to a strong inhibition of tumor cell proliferation.
Uses
Used in Anticancer Applications:
N2'-deacetyl-N2'-(3-Mercapto-1-oxopropyl)-Maytansine is used as an anticancer agent for its ability to inhibit tumor cell proliferation by targeting microtubules and tubulin. It is particularly effective in overcoming systemic toxicity associated with Maytansine and enhancing tumor-specific delivery when conjugated with monoclonal antibodies to form antibody-drug conjugates (ADCs).
Used in Drug Delivery Systems:
In the pharmaceutical industry, N2'-deacetyl-N2'-(3-Mercapto-1-oxopropyl)-Maytansine is used as a key component in the development of antibody-drug conjugates (ADCs) for targeted cancer therapy. These ADCs combine the tumor-specific targeting of monoclonal antibodies with the potent antineoplastic effects of Mertansine, improving the delivery, bioavailability, and therapeutic outcomes of the treatment.
Used in Organic Chemistry Research:
In the field of organic chemistry, N2'-deacetyl-N2'-(3-Mercapto-1-oxopropyl)-Maytansine serves as a valuable compound for research and development of new antineoplastic agents and drug delivery systems. Its unique chemical properties and potent biological activity make it an attractive candidate for further exploration and modification to develop more effective cancer treatments.
Biological Activity
Mertansine is a thiol-containing derivative of maytansine that is cytotoxic to human epidermoid carcinoma KB and human breast cancer SK-BR-3 cells (IC50 = 1.10 nM for both). Formulations containing mertansine have been studied for the treatment of multiple myeloma and squamous cell carcinoma.
Synthesis
Mertansine synthesis steps: A solution of N 2'-deacetyl-N 2'- (3-methyldithio-1-oxopropyl)- maytansine (2b) (1.95 g, 2.5 mmol) in a mixture of ethyl acetate (140 mL) and methanol (210 mL) was stirred at room temperature under an argon atmosphere and treated with a solution of dithiothreitol (0.95 g, 6.2 mmol) in 0.05 M potassium phosphate buffer (140 mL) at pH 7.5 containing 2 mM ethylenediaminetetraacetic acid (EDTA). The progress of the reaction was monitored by HPLC and was complete in three hours. The reaction mixture was treated with a solution of 0.2 M potassium phosphate buffer (250 mL) at pH 6.0 containing 2 mM EDTA and then extracted with ethyl acetate (3 x 600 mL). The organic layers were combined, washed with brine (100 mL), and then dried over sodium sulfate. Evaporation of the solvent gave a residue of crude thiol-containing maytansinoid 25a. The crude residue was purified by HPLC using a preparative Diazem cyano HPLC column (250 mm x 50 mm, 10 micron particle size) that was equilibrated in a mixture of hexanes/2-propanol/ethyl acetate (78.0:5.5:16.5, v/v/v) and run at a flow rate of 150 mL/min. The desired product 25a eluted as a peak centered at 16 min. The fractions containing the product were evaporated to give mertansine as a white solid (76% yield).Fig The synthetic method 1 of Mertansine.
Mode of action
Mertansine is a 19-member ansa macrolide structure attached to a chlorinated benzene ring. It was originally isolated from the shrub Maytenus ovatus. The antimitotic effect of maytansine has been attributed to its ability to inhibit microtubule assembly by binding to tubulin with a KD of ～1 μmol/L, at or near the vinblastine-binding site. Mertansine is effective in vivo against Lewis lung carcinoma and B16 murine melanocarcinoma solid tumors and has antileukemic activity against P388 murine lymphocytic leukemia.
Check Digit Verification of cas no
The CAS Registry Mumber 139504-50-0 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,3,9,5,0 and 4 respectively; the second part has 2 digits, 5 and 0 respectively.
Calculate Digit Verification of CAS Registry Number 139504-50:
(8*1)+(7*3)+(6*9)+(5*5)+(4*0)+(3*4)+(2*5)+(1*0)=130
130 % 10 = 0
So 139504-50-0 is a valid CAS Registry Number.
139504-50-0Relevant articles and documents
Photoactivatable prodrug for simultaneous release of mertansine and CO along with a BODIPY derivative as a luminescent marker in mitochondria: a proof of concept for NIR image-guided cancer therapy
Tiwari, Rajeshwari,Shinde, Prashant S.,Sreedharan, Sreejesh,Dey, Anik Kumar,Vallis, Katherine A.,Mhaske, Santosh B.,Pramanik, Sumit Kumar,Das, Amitava
, p. 2667 - 2673 (2021)
Controlled and efficient activation is the crucial aspect of designing an effective prodrug. Herein we demonstrate a proof of concept for a light activatable prodrug with desired organelle specificity. Mertansine, a benzoansamacrolide, is an efficient microtubule-targeting compound that binds at or near the vinblastine-binding site in the mitochondrial region to induce mitotic arrest and cell death through apoptosis. Despite its efficacy even in the nanomolar level, this has failed in stage 2 of human clinical trials owing to the lack of drug specificity and the deleterious systemic toxicity. To get around this problem, a recent trend is to develop an antibody-conjugatable maytansinoid with improved tumor/organelle-specificity and lesser systematic toxicity. Endogenous CO is recognized as a regulator of cellular function and for its obligatory role in cell apoptosis. CO blocks the proliferation of cancer cells and effector T cells, and the primary target is reported to be the mitochondria. We report herein a new mitochondria-specific prodrug conjugate (Pro-DC) that undergoes a photocleavage reaction on irradiation with a 400 nm source (1.0 mW cm?2) to induce a simultaneous release of the therapeutic components mertansine and CO along with a BODIPY derivative (BODIPY(PPH3)2) as a luminescent marker in the mitochondrial matrix. The efficacy of the process is demonstrated using MCF-7 cells and could effectively be visualized by probing the intracellular luminescence ofBODIPY(PPH3)2. This provides a proof-of-concept for designing a prodrug for image-guided combination therapy for mainstream treatment of cancer.
Maytansine dechloridation compound, intermediate, preparation method of compound and application
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Paragraph 0074; 0085-0106, (2020/12/09)
The invention discloses a maytansine dechloridation compound as shown in a formula I, an intermediate, a preparation method of the compound and an application. The invention provides the maytansine dechloridation compound as shown in the formula I. The maytansine dechloridation compound can be used as an impurity standard substance for impurity research of maytansine DM1 to establish an analysis method for maytansine DM1 quality control, and a proper method is selected to effectively remove the impurities. The quality of maytansine DM1 and even ADC drugs and the safety and effectiveness of clinical application can be improved. The invention also provides the preparation method and the intermediate of the maytansine dechloridation compound as shown in the formula I.
