Name: MC-Val-Cit-PAB-duocarmycin
Brand: BOC Sciences
Rating: 5 (1 reviews)

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

Shipping

Room temperature

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

What is MC-Val-Cit-PAB-duocarmycin?

MC-Val-Cit-PAB-duocarmycin is an ADC cytotoxin conjugate combining duocarmycin with a valine-citrulline-PAB linker. It is designed for controlled intracellular release following antibody-mediated endocytosis, providing targeted cytotoxic activity against cancer cells.

7/11/2018

Dear team, how does MC-Val-Cit-PAB-duocarmycin release duocarmycin?

The valine-citrulline-PAB linker in MC-Val-Cit-PAB-duocarmycin is cleaved by lysosomal proteases within target cells, releasing duocarmycin. This selective release ensures high cytotoxicity in tumor cells while minimizing systemic exposure.

25/8/2019

Dear team, what ADC research applications involve MC-Val-Cit-PAB-duocarmycin?

MC-Val-Cit-PAB-duocarmycin is used in preclinical and clinical ADC studies for solid tumors and hematologic malignancies. It allows evaluation of linker stability, intracellular payload release, and in vivo therapeutic efficacy of ADC constructs.

6/2/2022

May I ask what stability characteristics MC-Val-Cit-PAB-duocarmycin offers?

This conjugate maintains stability in plasma due to its valine-citrulline linker and robust conjugation chemistry, reducing premature drug release and improving the therapeutic index in ADC formulations.

22/5/2022

Good morning! Could you let me know if MC-Val-Cit-PAB-duocarmycin is compatible with multiple antibodies?

Yes, MC-Val-Cit-PAB-duocarmycin can be conjugated to cysteine residues of different monoclonal antibodies, enabling flexible ADC design, optimization of drug-antibody ratio, and adaptation for various tumor-targeting strategies.

10/8/2017

— Dr. Laura Bennett, Senior Scientist (USA)

MC-Val-Cit-PAB-duocarmycin purity and solubility were excellent for reproducible conjugation.

6/2/2022

— Dr. Michael Carter, ADC Chemist (UK)

Batch-to-batch consistency ensured reliable cytotoxicity assays.

10/8/2017

— Mr. Robert White, Principal Investigator (UK)

We tested MC-Val-Cit-PAB-duocarmycin from BOC Sciences in preclinical studies. The reproducibility of results was impressive, and the consistency between batches was a strong point. They truly understand ADC development needs.

22/5/2022

— Dr. David Chen, Director of R&D (United States)

Timelines are everything in drug development. We needed a high-purity batch of MC-Val-Cit-PAB-duocarmycin delivered quickly to meet our IND-enabling study schedule. BOC Sciences not only delivered ahead of time but also provided comprehensive COAs, giving us complete confidence in their product for our critical experiments.

7/11/2018

— Dr. Janek Kowalski, Senior Scientist (Poland)

Reliable and high-quality. The MC-Val-Cit-PAB-duocarmycin was exactly what we were looking for. The support team was also a pleasure to work with.

— Dr. Olivia Brown, Preclinical Researcher (USA)

We received MC-Val-Cit-PAB-duocarmycin on short notice, and BOC Sciences delivered without compromise on quality. The cytotoxic payload’s consistency accelerated our proof-of-concept studies.

25/8/2019