57103-68-1 Usage
Description
Maytansinol (Ansamitocin P-0), also known as Maytansine, O3-de2-(acetylmethylamino)-1-oxopropyl-, is a potent natural product derived from the maytansine family of compounds. It functions as an inhibitor of microtubule assembly, causing microtubule disassembly in vitro. This unique property makes it a valuable candidate for the development of targeted cancer therapies.
Uses
Used in Pharmaceutical Industry:
Maytansinol is utilized as an active pharmaceutical ingredient in the preparation of site-specific trastuzumab maytansinoid antibody-drug conjugates. These conjugates exhibit improved therapeutic activity against cancer cells, particularly in the treatment of solid malignancies. The conjugates leverage the natural microtubule-disrupting properties of maytansinol to enhance their efficacy in targeting and eliminating cancer cells.
The use of maytansinol in antibody-drug conjugates is supported by research published in the Journal of Medicinal Chemistry, which highlights its potential in improving cancer treatment outcomes (Pillow, T.H., et. al.: J. Med. Chem., 57, 7890 (2014)).
Biological Activity
Maytansinol is an ansamacrolide originally isolated from P. verrucose that has antimitotic and anticancer activities. It inhibits polymerization and induces depolymerization of bovine brain tubulin with EC50 values of 12 and 43 μM, respectively. Maytansinol inhibits sea urchin egg mitosis when used at a concentration of 10 μM and decreases proliferation of KB nasopharyngeal cancer cells (EC50 = 0.19 μg/ml).
Mode of action
Maytansinol (1 b) was first obtained by Kupchan et?al. both by isolation from Putterlickia verrucose and chemical removal of the acyl group from the hydroxy group at the C3 position. It showed weaker inhibitory activity on tubulin polymerization than maytansine, thus implying that the ester moiety at the C3 position of ansamitocins, maytansine, and maytansinoids plays an important role for biological activity and cell permeability. In fact, it has just recently been found that the carbonyl oxygen atom of the ester moiety forms a strong intramolecular interaction with the hydroxy group at position 9, fixing the bioactive conformation. Maytansinol has been regarded as a valuable precursor because acylation allows the preparation of both natural and new semisynthetic maytansinoids, differing in the ester side-chain substituents (Scheme 1). The acylation reaction of maytansinol is a crucial step in the preparation of maytansinoid ADCs or nanoparticles, constituting an uprising class of targeted cancer therapeutics. A few attempts to conjugate maytansinoids to peptides by this reaction have also been made very recently. Furthermore, considering that the maytansine binding site is one of the most recently identified and least explored on tubulin, acylation of maytansinol may serve for the preparation of useful molecular probes to better understand the structure-activity relationships of maytansinoids or to identify new maytansine-site ligands.Structure of maytansine (1 a), maytansinol (1 b), and the generic acylation reaction of maytansinol.
Check Digit Verification of cas no
The CAS Registry Mumber 57103-68-1 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 5,7,1,0 and 3 respectively; the second part has 2 digits, 6 and 8 respectively.
Calculate Digit Verification of CAS Registry Number 57103-68:
(7*5)+(6*7)+(5*1)+(4*0)+(3*3)+(2*6)+(1*8)=111
111 % 10 = 1
So 57103-68-1 is a valid CAS Registry Number.
InChI:InChI=1/C28H37ClN2O8/c1-15-8-7-9-22(37-6)28(35)14-20(38-26(34)30-28)16(2)25-27(3,39-25)21(32)13-23(33)31(4)18-11-17(10-15)12-19(36-5)24(18)29/h7-9,11-12,16,20-22,25,32,35H,10,13-14H2,1-6H3,(H,30,34)/b9-7+,15-8-
57103-68-1Relevant articles and documents
Structural requirements for antileukemic activity among the naturally occurring and semisynthetic maytansinoids.
Kupchan,Sneden,Branfman,Howie,Rebhun,McIvor,Wang,Schnaitman
, p. 31 - 37 (1978)
In an effort to determine the structural requirements for the significant antileukemic, cytotoxic, antitubulin, and antimitotic activity exhibited by the novel ansa macrolide, maytansine (1), four new C-3 ester and six new C-9 ether homologues were synthesized. The biological activities of these compounds were assayed and compared to the activities of previously reported, naturally occurring maytansinoids. From the data, it is apparent that presence of the C-3 ester is necessary for significant activity, and variations in the ester group are not accompanied by marked changes in activity. However, elimination of the ester group, as in maytansinol (7), maysine (8), normaysine (9), and maysenine (10), results in a significant decrease in biological activity. Blockage of the C-9 carbinolamide via etherification markedly reduces antileukemic and cytotoxic activity and slightly reduces antitubulin activity but has relatively little effect on antimitotic activity against sea urchin eggs. Thus, a free carbinolamide at C-9 is advantageous for optimal activity.
A highly potent maytansinoid analogue and its use as a cytotoxic therapeutic agent in gold nanoparticles for the treatment of hepatocellular carcinoma
Porter, John,Ding, Yao,Hale, Sarah J.M.,Perrins, Richard D.,Robinson, Angela,Mazanetz, Michael P.,Wu, Yubo,Ma, Yinping,Conlon, Kelly,Coulter, Tom
, (2020)
Gold nanoparticles are promising drug delivery agents with the potential to deliver chemotherapeutic agents to tumour sites. The highly cytotoxic maytansinoid tubulin inhibitor DM1 has been attached to gold nanoparticles and shows tumour growth inhibition in mouse models of hepatocellular carcinoma. Attempting to improve the stability of the gold-cytotoxin bond led to the design and synthesis of novel maytansinoids with improved potency in cell viability assays and improved in vivo tolerability compared to the DM1 analogues. These novel maytansines may also have applications in other methods of drug delivery, for example as the cytotoxic component of antibody drug conjugates.
Uses of immunoconjugates targeting CD138
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Page/Page column 12, (2018/11/23)
Disclosed is a method and composition for treating a disease associated with target cells expressing CD138 in a multiple dose regimen. An immunoconjugate comprising an engineered targeting antibody targeting CD138 expressing cells and an effector molecule is administered in a multiple dose regimen. The multiple dose regimen comprises at least two doses and the aggregate dose administered within an active treatment cycle is an aggregate maximum tolerable dose (AMTD) or a fraction of the AMTD. The AMTD and/or said fraction exceeds the dose resulting in dose limiting toxicity (DLT) and/or exceeds the maximum tolerable dose (MTD) when the immunoconjugate is administered as a single dose, including as part of a multiple single dose regimen within said active treatment cycle.
MAYTANSINOID ANALOGS AS ANTITUMOR AGENTS
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Page/Page column 9, (2008/06/13)
Ansamycin analogs, including maytansinoid analogs, and their use in treating cell proliferative diseases and conditions, and in particular, for use as antitumor agents.