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MedKoo Cat#: 123212 | Name: Mertansine (DM1)
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

Mertansine refers to the thiol-containing maytansinoid, DM1 (N2’-deacetyl-N2’-(3-mercapto-1-oxopropyl)maytansine) attached to a monoclonal antibody through reaction of the thiol group with an SPP (N-succinimidyl 4-(2-pyridyldithio)) linker to create an antibody-drug conjugate or ADC. Experimental ADCs with the SPP-DM1 design include lorvotuzumab mertansine. DM1 can also be linked to an antibody using the SMCC (4-(3-mercapto-2,5-dioxo-1-pyrrolidinylmethyl)-cylohexanecarboxylic acid) linker, in which case the International Nonproprietary Name of the conjugate formed contains the word emtansine. DM1 and its attachment via these linkers result from ImmunoGen Inc research. Trastuzumab emtansine (T-DM1) is an anti-HER2/neu antibody-drug conjugate.

Chemical Structure

Mertansine (DM1)
CAS#139504-50-0

Theoretical Analysis

MedKoo Cat#: 123212

Name: Mertansine (DM1)

CAS#: 139504-50-0

Chemical Formula: C35H48ClN3O10S

Exact Mass: 737.2749

Molecular Weight: 738.29

Elemental Analysis: C, 56.94; H, 6.55; Cl, 4.80; N, 5.69; O, 21.67; S, 4.34

Price and Availability

Size Price Availability Quantity
10mg USD 90.00 Ready to ship
25mg USD 150.00 Ready to ship
100mg USD 350.00 Ready to Ship
200mg USD 550.00 Ready to Ship
500mg USD 1,150.00 Ready to Ship
1g USD 2,050.00 Ready to ship
2g USD 3,690.00 Ready to Ship
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Synonym
DM1; DM-1; DM 1; DM1 Compound; DM1 [Maytansinoid]; Maytansinoid DM 1; Maytansinoid DM1; Maytansinoid DM-1; UNII-DDZ29HGH0E; maytansine, Mertansine; emtansine;
IUPAC/Chemical Name
(14S,16S,33S,2R,4R,10E,12Z,14R)-86-chloro-14-hydroxy-85,14-dimethoxy-33,2,7,10-tetramethyl-12,6-dioxo-7-aza-1(6,4)-oxazinana-3(2,3)-oxirana-8(1,3)-benzenacyclotetradecaphane-10,12-dien-4-yl N-(3-mercaptopropanoyl)-N-methyl-L-alaninate
InChi Key
ANZJBCHSOXCCRQ-GCRZMMRQSA-N
InChi Code
InChI=1S/C35H48ClN3O10S/c1-19-10-9-11-26(46-8)35(44)18-25(47-33(43)37-35)20(2)31-34(4,49-31)27(48-32(42)21(3)38(5)28(40)12-13-50)17-29(41)39(6)23-15-22(14-19)16-24(45-7)30(23)36/h9-11,15-16,20-21,25-27,31,44,50H,12-14,17-18H2,1-8H3,(H,37,43)/b11-9-,19-10+/t20-,21+,25+,26-,27-,31?,34+,35+/m1/s1
SMILES Code
C[C@@H]1[C@@H]2C[C@]([C@@H](/C=C\C=C(\CC3=CC(=C(C(=C3)OC)Cl)N(C(=O)C[C@H]([C@]4(C1O4)C)OC(=O)[C@H](C)N(C)C(=O)CCS)C)/C)OC)(NC(=O)O2)O
Appearance
White to off-white solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
Mertansine is a tubulin inhibitor, meaning that it inhibits the assembly of microtubules by binding to tubulin (at the rhizoxin binding site). The monoclonal antibody binds specifically to a structure (usually a protein) occurring in a tumour, thus directing mertansine into this tumour. This concept is called targeted therapy. The following (experimental) drugs are antibody-drug conjugates (ADC) combining monoclonal antibodies with mertansine as the cytotoxic component. Mertansine is linked via 4-mercaptovaleric acid.
Biological target:
Mertansine (DM1) is a microtubulin inhibitor and an antibody-conjugatable maytansinoid that is developed to overcome systemic toxicity associated with maytansine and to enhance tumor-specific delivery.
In vitro activity:
DM1 is a synthetic derivative of the tubulin-binding agent maytansine. Maytansine and the DM1 (S-methyl-DM1; ((N2’-deacetyl-N2’-(3-thiomethyl-1-oxopropyl)-maytansine; Fig. 1) suppress microtubule dynamics at very low drug concentrations. Maytansine as well as the DM1 derivative strongly suppress the dynamic instability parameters of microtubules assembled from MAP-free tubulin in vitro (Fig. 2). Maytansine and S-methyl-DM1 suppressed almost all dynamic instability parameters, including the growth rate, the shortening rate, the catastrophe frequency, and the rescue frequency, with the DM1 derivative showing stronger suppression of dynamics than the parent macrolide. The molecular mechanism of action of S-methyl-DM1 was found to be microtubule end poisoning. That is, S-methyl DM1 binds to the tips of microtubules and thereby inhibits the growth and the shortening of microtubules, leading to suppression of microtubule dynamics. Specifically, the maytansinoid showed high-affinity binding (KD, 0.1 μmol/L ) to approximately 37 sites per microtubule. Reference: Cancer Lett. 2011 Aug 28;307(2):113-8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3105156/
In vivo activity:
cRGD-decorated, redox-activatable micellar mertansine prodrug (cRGD-MMP) can effectively target and deliver DM1 to αvβ3 integrin overexpressing MDA-MB-231 TNBC xenografts in nude mice, resulting in potent tumor growth inhibition. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays showed that cRGD-MMP had obvious targetability to MDA-MB-231 cells with a low half-maximal inhibitory concentration (IC50) of 0.18 μM, which was close to that of free DM1 and 2.2-fold lower than that of micellar mertansine prodrug (MMP; nontargeting control). The confocal microscopy studies demonstrated that cRGD-MMP mediated a clearly more efficient cellular uptake and intracellular release of doxorubicin (used as a fluorescent anticancer drug model) in MDA-MB-231 cells. Notably, cRGD-MMP loaded with 1,1'-dioctadecyltetramethyl indotricarbocyanine iodide (DiR; a hydrophobic near-infrared dye) was shown to quickly accumulate in the MDA-MB-231 tumor with strong DiR fluorescence from 2 to 24 h post injection. MMP loaded with DiR could also accumulate in the tumor, although significantly less than cRGD-MMP. The biodistribution studies revealed a high DM1 accumulation of 8.1%ID/g in the tumor for cRGD-MMP at 12 h post injection. The therapeutic results demonstrated that cRGD-MMP effectively suppressed MDA-MB-231 tumor growth at 1.6 mg DM1 equiv./kg without causing noticeable side effects, as shown by little body weight loss and histological analysis. This MMP has appeared as a promising platform for potent treatment of TNBCs. Reference: Int J Nanomedicine. 2017 Oct 27;12:7913-7921. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5667790/
Solvent mg/mL mM comments
Solubility
DMSO 60.0 81.26
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 738.29 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
1. Lopus M. Antibody-DM1 conjugates as cancer therapeutics. Cancer Lett. 2011 Aug 28;307(2):113-8. doi: 10.1016/j.canlet.2011.03.017. Epub 2011 Apr 9. PMID: 21481526; PMCID: PMC3105156. 2. Zhong P, Gu X, Cheng R, Deng C, Meng F, Zhong Z. αvβ3 integrin-targeted micellar mertansine prodrug effectively inhibits triple-negative breast cancer in vivo. Int J Nanomedicine. 2017 Oct 27;12:7913-7921. doi: 10.2147/IJN.S146505. PMID: 29138558; PMCID: PMC5667790.
In vitro protocol:
1. Lopus M. Antibody-DM1 conjugates as cancer therapeutics. Cancer Lett. 2011 Aug 28;307(2):113-8. doi: 10.1016/j.canlet.2011.03.017. Epub 2011 Apr 9. PMID: 21481526; PMCID: PMC3105156.
In vivo protocol:
1. Zhong P, Gu X, Cheng R, Deng C, Meng F, Zhong Z. αvβ3 integrin-targeted micellar mertansine prodrug effectively inhibits triple-negative breast cancer in vivo. Int J Nanomedicine. 2017 Oct 27;12:7913-7921. doi: 10.2147/IJN.S146505. PMID: 29138558; PMCID: PMC5667790.
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