Name: DM1-SMe
Brand: BOC Sciences
Price: 519 USD
Availability: MadeToOrder

Synonyms

DM1-SMe; DM1-SSMe; maytansinoid derivative with ADC linker. Maytansine or mertansine or emtansine derivative; N2'-deacetyl-N2'-[3-(methyldithio)-1-oxopropyl]maytansine.

IUPAC Name

[(1S,2R,3S,5S,6S,16Z,18Z,20R,21S)-11-chloro-21-hydroxy-12,20-dimethoxy-2,5,9,16-tetramethyl-8,23-dioxo-4,24-dioxa-9,22-diazatetracyclo[19.3.1.110,14.03,5]hexacosa-10,12,14(26),16,18-pentaen-6-yl] (2S)-2-[methyl-[3-(methyldisulfanyl)propanoyl]amino]propanoate

Canonical SMILES

CC1C2CC(C(C=CC=C(CC3=CC(=C(C(=C3)OC)Cl)N(C(=O)CC(C4(C1O4)C)OC(=O)C(C)N(C)C(=O)CCSSC)C)C)OC)(NC(=O)O2)O

InChI

InChI=1S/C36H50ClN3O10S2/c1-20-11-10-12-27(47-8)36(45)19-26(48-34(44)38-36)21(2)32-35(4,50-32)28(49-33(43)22(3)39(5)29(41)13-14-52-51-9)18-30(42)40(6)24-16-23(15-20)17-25(46-7)31(24)37/h10-12,16-17,21-22,26-28,32,45H,13-15,18-19H2,1-9H3,(H,38,44)/b12-10-,20-11-/t21-,22+,26+,27-,28+,32+,35+,36+/m1/s1

InChIKey

ZLUUPZXOPGORNG-UDXCHANISA-N

Solubility

Soluble in DMSO, not in water

Appearance

Soild powder

Shelf Life

2 years if stored properly

Shipping

Room temperature

Storage

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

In Vitro

Structure-activity-relationship studies had identified the C3 ester side chain as a critical element for antitumor activity of maytansinoids. The maytansinoids bearing the methyl group at C3 position with D configuration were about 100 to 400-fold less cytotoxic than their corresponding L-epimers toward various cell lines. IMGN901 and DM1-SMe (unconjugated DM1 as a mixed disulfide with thiomethane to cap its sulfhydryl group) were tested in vitro at concentrations ranging from 0.01 nM to 0.1 µM and 0.3 pM to 3 nM, respectively. IMGN901 was tested against a subset of PPTP solid tumor xenografts focusing on those with high CD56 expression.The combination of IMGN901 with topotecan was also evaluated.

In Vivo

Neuroblastoma models expressed CD56 at or above the median expression level for all PPTP xenografts and cell lines. Neuroblastoma cell lines demonstrated relatively low sensitivity to DM1-SMe compared to other cell lines, but the sensitivity of neuroblastoma cell lines to IMGN901 was comparable to that of non-neuroblastoma cell lines. In vivo, objective responses were observed in 9 of 24 (38%) models including, three of seven neuroblastoma xenografts, and two of seven rhabdomyosarcoma xenografts. All xenografts with objective responses showed homogeneous high-level staining by IHC for CD56, but not all xenografts with homogenous high-level staining had objective responses. Combined with topotecan, IMGN901 demonstrated therapeutic enhancement against two of four neuroblastoma models.

DM1-SMe, a potent cytotoxic agent, is instrumental in the development of antibody-drug conjugates (ADCs) and cancer research. Here are four key applications of DM1-SMe:

Antibody-Drug Conjugates (ADCs): Serving as the cytotoxic warhead in ADCs for targeted cancer therapy, DM1-SMe is a cornerstone of innovation. By conjugating DM1-SMe to specific antibodies, researchers can precisely deliver the drug to cancer cells while safeguarding healthy tissues. This targeted approach heightens the effectiveness of cancer treatments while mitigating systemic toxicity.

Cancer Cell Line Studies: In the realm of preclinical research, DM1-SMe stands as a powerhouse tool for examining the impact of potent cytotoxic agents on cancer cell lines. Researchers expose diverse cancer cell cultures to DM1-SMe to elucidate its anti-proliferative properties and unravel the mechanisms of cell death.

Drug Resistance Studies: Unveiling the intricate web of drug resistance mechanisms in cancer cells, DM1-SMe emerges as a crucial investigative tool. Through the exposure of resistant cancer cell lines to DM1-SMe, scientists delve into the genetic and biochemical pathways underlying resistance. This in-depth insight serves as a foundation for crafting novel strategies to surmount resistance hurdles and elevate the efficacy of cancer therapies, driving innovation in cancer treatment paradigms.

Pharmacokinetic and Toxicology Studies: Embarking on a journey through pharmacokinetic and toxicology landscapes, DM1-SMe takes center stage in unraveling its behavior within biological systems. Researchers meticulously analyze the distribution, metabolism, and excretion patterns of DM1-SMe in animal models to delineate its safety profile. These studies yield pivotal data essential for designing safer and more efficacious chemotherapy regimens, forging a path towards enhanced patient outcomes and improved treatment protocols.

1.Initial testing (Stage 1) of the antibody-maytansinoid conjugate, IMGN901 (Lorvotuzumab mertansine), by the pediatric preclinical testing program.

Wood AC;Maris JM;Gorlick R;Kolb EA;Keir ST;Reynolds CP;Kang MH;Wu J;Kurmasheva RT;Whiteman K;Houghton PJ;Smith MA Pediatr Blood Cancer. 2013 Nov;60(11):1860-7. doi: 10.1002/pbc.24647. Epub 2013 Jun 24.

BACKGROUND: ;IMGN901 (lorvotuzumab mertansine) is an antibody-drug conjugate composed of a humanized antibody that specifically binds to CD56 (NCAM, neural cell adhesion molecule) and that is conjugated to the maytansinoid, DM1 (a microtubule targeting agent).;PROCEDURES: ;IMGN901 and DM1-SMe (unconjugated DM1 as a mixed disulfide with thiomethane to cap its sulfhydryl group) were tested in vitro at concentrations ranging from 0.01 nM to 0.1 µM and 0.3 pM to 3 nM, respectively. IMGN901 was tested against a subset of PPTP solid tumor xenografts focusing on those with high CD56 expression.The combination of IMGN901 with topotecan was also evaluated.;RESULTS: ;Neuroblastoma models expressed CD56 at or above the median expression level for all PPTP xenografts and cell lines. Neuroblastoma cell lines demonstrated relatively low sensitivity to DM1-SMe compared to other cell lines, but the sensitivity of neuroblastoma cell lines to IMGN901 was comparable to that of non-neuroblastoma cell lines. In vivo, objective responses were observed in 9 of 24 (38%) models including, three of seven neuroblastoma xenografts, and two of seven rhabdomyosarcoma xenografts. All xenografts with objective responses showed homogeneous high-level staining by IHC for CD56, but not all xenografts with homogenous high-level staining had objective responses.

Catalog	Product Name	CAS
BADC-01450	MCC-DM1	1100692-14-5
BADC-00009	DM1-SMCC	1228105-51-8
BADC-00574	Lys-SMCC-DM1	1281816-04-3
BADC-00848	MC-DM1	1375089-56-7
BADC-00601	Mal-VC-PAB-DM1	1464051-44-2
BADC-00668	SC-VC-PAB-DM1	2259318-47-1
BADC-00010	DM1-SPP	452072-20-7
BADC-01378	S-methyl DM1	912569-84-7
BADC-01407	SPDB-DM1
BADC-01411	MPB-VC-PAB-DM1

What is the role of DM1-SMe in an ADC?

DM1-SMe is a highly potent cytotoxic maytansinoid derivative used as a payload in antibody-drug conjugates. Its primary function is to inhibit microtubule assembly, leading to cell death. When conjugated to a target-specific antibody, DM1-SMe can be delivered selectively to cancer cells, maximizing its therapeutic effect while sparing healthy tissue.

20/5/2018

We would like to know how the mechanism of DM1-SMe differs from other payloads.

DM1-SMe is a tubulin polymerization inhibitor, which is a common mechanism for maytansinoid payloads. Its specific structure and properties, however, make it particularly effective. The payload is released intracellularly through the cleavage of a specific linker, enabling it to disrupt the cell's microtubule network and induce apoptosis with high efficiency.

22/2/2019

Dear BOC Sciences, what type of linker is used with DM1-SMe in ADCs?

DM1-SMe is typically conjugated to antibodies via a stable thioether linker. This type of linker is designed to be highly stable in systemic circulation, preventing premature release of the cytotoxic payload. The stability ensures that the payload is released primarily within the target cell, where a specific mechanism, such as lysosomal degradation, facilitates its release.

16/3/2021

Why is DM1-SMe considered a preferred payload in certain ADC designs?

DM1-SMe is a preferred payload for its potent cytotoxicity and favorable pharmacokinetic properties. Its conjugation to an antibody through a stable linker minimizes off-target toxicity, while its high potency ensures that a small amount of payload can have a significant therapeutic impact. This combination is crucial for developing safe and effective targeted therapies.

9/6/2016

Dear team, how is the potency of DM1-SMe typically characterized?

The potency of DM1-SMe is characterized by its very low IC50 values in a range of human tumor cell lines, indicating its high cytotoxicity. This potency is significantly greater than that of its parent compound, Maytansine. The high intrinsic potency of DM1-SMe is a critical factor in its efficacy as an ADC payload.

19/9/2021

— Dr. David Miller, Senior ADC Researcher (USA)

DM1-SMe delivered by BOC Sciences showed high purity, supporting precise ADC conjugation.

16/3/2021

— Dr. Alice Johnson, Medicinal Chemist (UK)

Batch-to-batch consistency of DM1-SMe allowed reproducible in vitro studies.

19/9/2021

— Dr. Felix Schneider, Biochemist (Germany)

Fast delivery and thorough QC documentation for DM1-SMe streamlined workflow planning.

9/6/2016

— Dr. Sophie Wilson, Senior Scientist (Canada)

Reliable DM1-SMe quality enabled reproducible ADC conjugation results.