Name: MC-Sq-Cit-PAB-Gefitinib
Brand: BOC Sciences
Rating: 5 (1 reviews)

Synonyms

MC Sq Cit PAB Gefitinib

IUPAC Name

1-N'-[(2S)-5-(carbamoylamino)-1-[4-[[4-(3-chloro-4-fluoroanilino)-7-methoxy-6-(3-morpholin-4-ylpropoxy)quinazolin-1-ium-1-yl]methyl]anilino]-1-oxopentan-2-yl]-1-N-[5-(2,5-dioxopyrrol-1-yl)pentyl]cyclobutane-1,1-dicarboxamide

Canonical SMILES

COC1=CC2=[N+](CC3=CC=C(NC([C@@H](NC(C4(C(NCCCCCN5C(C=CC5=O)=O)=O)CCC4)=O)CCCNC(N)=O)=O)C=C3)C=NC(NC6=CC=C(F)C(Cl)=C6)=C2C=C1OCCCN7CCOCC7

InChI

InChI=1S/C50H60ClFN10O9/c1-69-41-30-40-36(29-42(41)71-25-7-21-60-23-26-70-27-24-60)45(57-35-13-14-38(52)37(51)28-35)56-32-61(40)31-33-9-11-34(12-10-33)58-46(65)39(8-5-20-55-49(53)68)59-48(67)50(17-6-18-50)47(66)54-19-3-2-4-22-62-43(63)15-16-44(62)64/h9-16,28-30,32,39H,2-8,17-27,31H2,1H3,(H6,53,54,55,58,59,65,66,67,68)/p+1/t39-/m0/s1

Shipping

Room temperature

MC-Sq-Cit-PAB-Gefitinib is a conjugate that combines the potent anticancer drug gefitinib with a targeted delivery system to enhance its specificity and efficacy in cancer therapy. Gefitinib is an epidermal growth factor receptor (EGFR) inhibitor commonly used in the treatment of non-small cell lung cancer (NSCLC) and other EGFR-driven cancers. When conjugated to a peptide or antibody linker, such as the MC-Sq-Cit-PAB component, gefitinib's delivery is more targeted, reducing systemic side effects and improving therapeutic outcomes. This conjugate represents a promising approach for enhancing the precision of cancer treatments.

One of the primary applications of MC-Sq-Cit-PAB-Gefitinib is in the development of antibody-drug conjugates (ADCs) for targeted cancer therapy. By linking gefitinib to a peptide or antibody that selectively binds to specific cancer cell markers, this conjugate ensures that the drug is delivered directly to the tumor site. This increases the concentration of gefitinib at the tumor while reducing exposure to healthy tissues. The targeted delivery system improves the overall efficacy of gefitinib by overcoming issues like drug resistance and non-selective cytotoxicity, which are common with traditional chemotherapy.

MC-Sq-Cit-PAB-Gefitinib is also applied in improving the pharmacokinetics of gefitinib. Traditional oral administration of gefitinib may result in suboptimal bioavailability or systemic toxicity. However, by conjugating gefitinib to a specialized carrier molecule such as MC-Sq-Cit-PAB, the drug's stability, solubility, and bioavailability are enhanced. This conjugation strategy also enables controlled release at the tumor site, optimizing the therapeutic dose delivered to cancer cells while minimizing side effects. Researchers are exploring MC-Sq-Cit-PAB-Gefitinib in preclinical models to refine its pharmacokinetic profile and extend its therapeutic potential.

Another important application of MC-Sq-Cit-PAB-Gefitinib is in overcoming drug resistance mechanisms. Many cancers develop resistance to gefitinib and other EGFR inhibitors through various mechanisms, such as mutations in the EGFR gene. The targeted delivery of gefitinib via MC-Sq-Cit-PAB can potentially bypass some of these resistance pathways by ensuring that the drug is specifically delivered to the tumor cells, where it can exert its therapeutic effects. This approach could offer a solution for patients with resistant cancer strains, expanding the range of patients who can benefit from EGFR-targeted therapies.

1.Quaternary amine compounds and antibody-drug conjugates thereof

FLYGARE, John A, et al.

This invention relates to antibody-drug conjugates represented by Formula (I) Ab- (L-D)p, Ab is an antibody; p is 1-8; L-D is a chemical moiety represented by the following formula -Str-(Pep)-Sp-D; Str is a stretcher unit covalently attached to Ab; Pep is a linker; D is anti-tumor agent represented by the following formula wherein R<20>and R<30>are each independently Ct-C6alkyl, and R<10>is a non-hydrogen substituent; or R<30>is C1-C6alkyl, and R<10>and R<20>together with the N form a substituted C3-C7heterocycloalkyl ring; or R<3>° is absent, and R<10>and R<20>together with the N form a substituted heteroaryl ring; Sp-D is a spacer moiety of fomula: This invention also relates to a method of treating cancer, use of antibody-drug conjugates of Formula (I) in therapy, and use of antibody-drug conjugates of Formula (I) in manufacturing a medicament for treating cancer. This invention also relates to method of preparing antibody-drug conjugates of Formula (I).

2.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	Inquiry
BADC-01475	N3-PEG8-Phe-Lys-PABC-Gefitinib

What is MC-Sq-Cit-PAB-Gefitinib?

MC-Sq-Cit-PAB-Gefitinib is a small-molecule ADC linker-payload conjugate, integrating gefitinib with a squaric acid-based citrulline-PAB linker. It is designed for selective intracellular delivery in ADC applications, combining targeted therapy with cytotoxic activity.

1/12/2019

We are interested in how MC-Sq-Cit-PAB-Gefitinib releases its payload.

The citrulline-PAB linker in MC-Sq-Cit-PAB-Gefitinib is cleaved by intracellular proteases, releasing gefitinib in the cytoplasm of target cells. This protease-sensitive mechanism ensures precise payload delivery while reducing systemic effects.

2/2/2017

Could you advise what ADC applications utilize MC-Sq-Cit-PAB-Gefitinib?

MC-Sq-Cit-PAB-Gefitinib is applied in oncology ADC research to combine small-molecule inhibitors with targeted antibody delivery. Its linker design allows evaluation of drug release kinetics, ADC stability, and tumor-specific cytotoxicity in preclinical studies.

26/3/2016

Could you please let me know what chemical features make MC-Sq-Cit-PAB-Gefitinib effective?

The squaric acid conjugation enhances linker stability, while the citrulline-PAB sequence ensures protease-sensitive release of gefitinib. This structure improves ADC solubility, circulation stability, and targeted intracellular delivery.

10/12/2022

Dear team, can MC-Sq-Cit-PAB-Gefitinib be conjugated to different antibodies?

Yes, its squaric acid functional group allows conjugation to multiple antibody types, supporting flexible ADC design. This enables optimization of drug-antibody ratios, targeting specificity, and controlled payload release for therapeutic studies.

17/12/2022

— Dr. James Parker, Senior Scientist (USA)

MC-Sq-Cit-PAB-Gefitinib demonstrated excellent purity for reproducible ADC conjugation.

26/3/2016

— Dr. Olivia Harris, ADC Chemist (UK)

Batch uniformity ensured consistent cytotoxicity and conjugation results.

17/12/2022

— Dr. Sofia Alvarez, Oncology Researcher (Spain)

BOC Sciences supplied us with MC-Sq-Cit-PAB-Gefitinib, which was instrumental for our conjugation trials. The compound showed high stability under different conditions, helping us accelerate decision-making in early-stage studies.

10/12/2022

— Mr. Alex Ivanov, Biochemist (Russia)

Our project required a custom linker with an innovative cleavable component. BOC Sciences' MC-Sq-Cit-PAB-Gefitinib stood out for its unique structure and purity. The product performed exceptionally well in our cellular assays, showing great stability and targeted release. A truly novel and effective linker.

1/12/2019

— Mr. Liam O'Connor, Biochemist (Ireland)

The unique structure of this linker was key to our novel ADC design. MC-Sq-Cit-PAB-Gefitinib from BOC Sciences performed flawlessly in our studies.

— Dr. Marco Ricci, Senior Investigator (Italy)

Our group tested MC-Sq-Cit-PAB-Gefitinib sourced from BOC Sciences. It demonstrated predictable performance and enabled clear results in mechanistic assays, adding confidence to our ADC pipeline.

2/2/2017