Name: MC-Val-Cit-PAB-duocarmycin
Brand: BOC Sciences
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Synonyms

MC Val Cit PAB duocarmycin

IUPAC Name

[4-[[(2S)-5-(carbamoylamino)-2-[[(2S)-2-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]-3-methylbutanoyl]amino]pentanoyl]amino]phenyl]methyl-[2-[[2-[(1S)-1-(chloromethyl)-5-hydroxy-1,2-dihydrobenzo[e]indole-3-carbonyl]-1H-indol-5-yl]oxy]ethyl]-dimethylazanium

Canonical SMILES

ClC[C@H]1C2=C(C=C(O)C3=CC=CC=C23)N(C(C4=CC5=CC(OCC[N+](C)(C)CC6=CC=C(NC([C@H](CCCNC(N)=O)NC([C@H](C(C)C)NC(CCCCCN7C(C=CC7=O)=O)=O)=O)=O)C=C6)=CC=C5N4)=O)C1

InChI

InChI=1S/C54H64ClN9O9/c1-33(2)50(61-46(66)14-6-5-9-24-62-47(67)21-22-48(62)68)52(70)60-42(13-10-23-57-54(56)72)51(69)58-37-17-15-34(16-18-37)32-64(3,4)25-26-73-38-19-20-41-35(27-38)28-43(59-41)53(71)63-31-36(30-55)49-40-12-8-7-11-39(40)45(65)29-44(49)63/h7-8,11-12,15-22,27-29,33,36,42,50H,5-6,9-10,13-14,23-26,30-32H2,1-4H3,(H7-,56,57,58,59,60,61,65,66,69,70,71,72)/p+1/t36-,42+,50+/m1/s1

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MC-Val-Cit-PAB-duocarmycin is a powerful targeted drug conjugate that combines the potent DNA-intercalating agent duocarmycin with a selective peptide linker. Duocarmycin is known for its ability to bind to DNA and induce strand breaks, which disrupts DNA replication and leads to cell death, particularly in rapidly dividing cancer cells. The conjugation of duocarmycin with the MC-Val-Cit-PAB linker enables the precise delivery of this cytotoxic agent directly to tumor cells, significantly improving the therapeutic index by concentrating the drug at the tumor site while minimizing systemic toxicity.

One of the primary applications of MC-Val-Cit-PAB-duocarmycin is in the development of antibody-drug conjugates (ADCs) for targeted cancer therapy. The peptide linker allows for selective targeting of cancer cells that overexpress specific cell surface markers, ensuring that duocarmycin is delivered specifically to tumor cells. This targeted approach enhances the effectiveness of duocarmycin by ensuring it is concentrated where it is needed most, while reducing damage to healthy tissues. This makes MC-Val-Cit-PAB-duocarmycin an attractive candidate for treating cancers that are resistant to conventional chemotherapies.

In addition to its use in ADCs, MC-Val-Cit-PAB-duocarmycin offers an innovative strategy to overcome drug resistance in cancer therapy. Many tumors develop resistance to traditional chemotherapeutic agents due to the inability of drugs to specifically target cancer cells. By using a targeted delivery system, MC-Val-Cit-PAB-duocarmycin bypasses some of the common resistance mechanisms, ensuring that the cytotoxic agent is delivered directly to the cancer cells. This targeted mechanism may help improve the efficacy of treatment, even in cases where resistance to other therapies has developed.

MC-Val-Cit-PAB-duocarmycin also demonstrates the potential to enhance the pharmacokinetics of duocarmycin. Traditional chemotherapy with duocarmycin and other DNA-damaging agents often suffers from poor bioavailability, short half-lives, and high systemic toxicity. The MC-Val-Cit-PAB linker improves the solubility and stability of duocarmycin, allowing for more efficient delivery to the tumor. This controlled release system ensures that the drug is active longer and reaches the cancerous tissue with greater precision, leading to enhanced therapeutic outcomes with fewer side effects.

1.Targeted drug delivery through the traceless release of tertiary and heteroaryl amines from antibody-drug conjugates

Staben LR, et al.

The reversible attachment of a small-molecule drug to a carrier for targeted delivery can improve pharmacokinetics and the therapeutic index. Previous studies have reported the delivery of molecules that contain primary and secondary amines via an amide or carbamate bond; however, the ability to employ tertiary-amine-containing bioactive molecules has been elusive. Here we describe a bioreversible linkage based on a quaternary ammonium that can be used to connect a broad array of tertiary and heteroaryl amines to a carrier protein. Using a concise, protecting-group-free synthesis we demonstrate the chemoselective modification of 12 complex molecules that contain a range of reactive functional groups. We also show the utility of this connection with both protease-cleavable and reductively cleavable antibody-drug conjugates that were effective and stable in vitro and in vivo. Studies with a tertiary-amine-containing antibiotic show that the resulting antibody-antibiotic conjugate provided appropriate stability and release characteristics and led to an unexpected improvement in activity over the conjugates previously connected via a carbamate.

Catalog	Product Name	CAS
BADC-00811	Duocarmycin DM free base	1116745-06-2
BADC-00337	Seco-Duocarmycin TM	1142188-60-0
BADC-00223	Duocarmycin A	118292-34-5
BADC-00362	Duocarmycin B1	124325-93-5
BADC-00341	Seco-Duocarmycin SA	152785-82-5
BADC-00605	Duocarmycin TM	157922-77-5
BADC-00332	Seco-DuocarmycinCN	1613286-54-6
BADC-00333	Seco-DuocarmycinDMG	1613286-55-7
BADC-00342	Seco-Duocarmycin MA	1613286-57-9
BADC-00609	Duocarmycin MB	1613286-58-0