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MPB-VC-PAB-DM1

  CAS No.:   Cat No.: BADC-01411 4.5  

MPB-VC-PAB-DM1 is a thiol-reactive drug-linker conjugate used in the synthesis of antibody-drug conjugates (ADCs).

MPB-VC-PAB-DM1

Structure of

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ADC Cytotoxin with Linker
Molecular Formula
C65H82ClN9O17
Molecular Weight
1296.87

* For research and manufacturing use only. We do not sell to patients.

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IUPAC Name
(14S,16S,32S,33S,2R,4S,10E,12E,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-(((4-((S)-2-((S)-2-(4-(4-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)phenyl)butanamido)-3-methylbutanamido)-5-ureidopentanamido)benzyl)oxy)carbonyl)-N-methyl-L-alaninate
InChI
InChI=1S/C65H82ClN9O17/c1-36(2)56(71-51(76)18-12-15-40-21-25-44(26-22-40)75-52(77)27-28-53(75)78)59(81)70-45(16-13-29-68-61(67)83)58(80)69-43-23-19-41(20-24-43)35-89-63(85)73(7)39(5)60(82)91-50-33-54(79)74(8)46-31-42(32-47(87-9)55(46)66)30-37(3)14-11-17-49(88-10)65(86)34-48(90-62(84)72-65)38(4)57-64(50,6)92-57/h11,14,17,19-28,31-32,36,38-39,45,48-50,56-57,86H,12-13,15-16,18,29-30,33-35H2,1-10H3,(H,69,80)(H,70,81)(H,71,76)(H,72,84)(H3,67,68,83)/b17-11+,37-14+/t38-,39+,45+,48+,49-,50+,56+,57+,64+,65+/m1/s1
InChIKey
OXFFVXZIYNKAAK-GDHWPVNGSA-N

MPB-VC-PAB-DM1 is a sophisticated thiol-reactive drug-linker conjugate that has become instrumental in the development of antibody-drug conjugates (ADCs), a class of biopharmaceuticals that offer targeted cancer therapy. The conjugate integrates multiple components that contribute to its efficacy and precision: the potent cytotoxic agent DM1, a derivative of maytansine that inhibits microtubule assembly, is connected to antibodies via the linker sequence MPB-VC-PAB. This combination facilitates the selective delivery of DM1 to cancer cells, significantly improving the therapeutic index by concentrating the cytotoxic effect on malignant cells while minimizing damage to healthy tissues.

The MPB components in MPB-VC-PAB-DM1 provide a thiol-reactive maleimide group that enables stable conjugation with cysteine residues on monoclonal antibodies. This covalent attachment ensures that the drug-linker payload remains securely bound to the antibody as it circulates in the bloodstream, thus preventing premature drug release. The integrity of this bond is crucial for ensuring that DM1's potent cytotoxic actions are only unleashed upon internalization by target cells. This selectivity is further enhanced by the targeting capability of the antibody, which binds to specific antigens expressed on the surface of cancer cells, directing the ADC precisely where it is needed.

The VC-PAB linker in MPB-VC-PAB-DM1 plays a critical role in the controllable release of DM1 inside target cells. The valine-citrulline (VC) dipeptide is a protease-cleavable moiety specifically designed to be stable in the bloodstream yet responsive to enzymatic activity inside lysosomes of targeted cancer cells, where cathepsins cleave the linker, triggering the release of DM1. Moreover, the para-aminobenzyl alcohol (PAB) spacer serves as a self-immolative moiety that ensures the complete release of active DM1 upon enzymatic cleavage. This dual-functionality design allows for a precise drug release mechanism, thereby enhancing the ADC's ability to eradicate tumor cells effectively.

MPB-VC-PAB-DM1 is widely applicable in treating various aggressive cancers that express specific antigens matched by the conjugated antibodies. Its use in clinical and preclinical trials has shown promise in treating cancers such as breast cancer, non-small cell lung cancer, and other solid tumors. By selectively targeting cancer cells and sparing healthy tissues, MPB-VC-PAB-DM1-based ADCs offer higher efficacy and reduced toxicity compared to traditional chemotherapies. Researchers continue to explore further refinements in linker technology and antibody targeting to expand its therapeutic applications, aiming to address resistance mechanisms and improve patient outcomes. As a result, MPB-VC-PAB-DM1 stands out as a key component in the arsenal of targeted cancer therapies, driving advancements towards more personalized and effective cancer treatments.

The molarity calculator equation

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

The dilution calculator equation

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

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