Name: MC-GGFG-DX8951
Brand: BOC Sciences
Rating: 5 (1 reviews)

Synonyms

6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-N-(2-((2-(((S)-1-((2-(((1R,9S)-9-ethyl-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-1-yl)amino)-2-oxoethyl)amino)-1-oxo-3-phenylpropan-2-yl)amino)-2-oxoethyl)amino)-2-oxoethyl)hexanamide; MC-GGFG-DX8951; MC-GGFG-DX-8951; MC-GGFG-DX 8951; MC-GGFG-DX.

IUPAC Name

6-(2,5-dioxopyrrol-1-yl)-N-[2-[[2-[[(2S)-1-[[2-[[(10S,23S)-10-ethyl-18-fluoro-10-hydroxy-19-methyl-5,9-dioxo-8-oxa-4,15-diazahexacyclo[14.7.1.02,14.04,13.06,11.020,24]tetracosa-1,6(11),12,14,16,18,20(24)-heptaen-23-yl]amino]-2-oxoethyl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-2-oxoethyl]amino]-2-oxoethyl]hexanamide

Canonical SMILES

O=C1[C@](O)(CC)C2=C(CO1)C(N3CC4=C5C6=C(CC[C@@H]5NC(CNC([C@H](CC7=CC=CC=C7)NC(CNC(CNC(CCCCCN8C(C=CC8=O)=O)=O)=O)=O)=O)=O)C(C)=C(F)C=C6N=C4C3=C2)=O

InChI

InChI=1S/C49H51FN8O11/c1-3-49(68)31-19-36-45-29(24-58(36)47(66)30(31)25-69-48(49)67)44-33(14-13-28-26(2)32(50)20-34(56-45)43(28)44)54-40(62)23-53-46(65)35(18-27-10-6-4-7-11-27)55-39(61)22-52-38(60)21-51-37(59)12-8-5-9-17-57-41(63)15-16-42(57)64/h4,6-7,10-11,15-16,19-20,33,35,68H,3,5,8-9,12-14,17-18,21-25H2,1-2H3,(H,51,59)(H,52,60)(H,53,65)(H,54,62)(H,55,61)/t33-,35+,49+/m1/s1

InChIKey

XEKFDUNPKACYAY-UAVZYSABSA-N

Shipping

Room temperature, or blue ice upon request.

MC-GGFG-DX8951 represents a novel advancement in the field of targeted cancer therapeutics, serving as a pivotal compound for the development of DX8951-based antibody-drug conjugates (ADCs). These conjugates are designed to selectively deliver the potent anticancer agent DX8951 directly to tumor cells. The use of a peptidyl spacer, specifically Gly-Gly-Phe-Gly, connects DX8951 covalently, ensuring that the drug remains stable during circulation, significantly reducing systemic toxicity. This stability is crucial for minimizing side-effects often associated with chemotherapy and improving patient quality of life

The mechanism of action for MC-GGFG-DX8951 begins with its incorporation into an ADC, which involves linking the drug to a monoclonal antibody that specifically targets antigens expressed on cancer cells. Once the ADC binds to the tumor cell surface, it undergoes internalization primarily through receptor-mediated endocytosis. Inside the tumor cells, the MC-GGFG linker is cleaved by lysosomal enzymes. This enzymatic cleavage is a critical step, releasing DX8951 in its active form directly within the lysosome, thereby achieving a more effective and targeted cytotoxic effect. This approach not only enhances the drug concentration at the tumor site but also mitigates adverse effects on healthy tissues

MC-GGFG-DX8951 is particularly valuable in the context of solid tumors where conventional therapies have limited efficacy. Its application in ADC technology allows for the personalization of cancer treatment, enabling therapies to be tailored based on the specific molecular profiles of tumors. This approach can lead to improved response rates and outcomes in patients who are resistant to standard chemotherapeutic agents. Furthermore, by leveraging the antigen-specific targeting capabilities of monoclonal antibodies, MC-GGFG-DX8951-based ADCs exhibit a higher specificity, reducing off-target effects and enhancing the therapeutic index

1.Novel antibody drug conjugates containing exatecan derivative-based cytotoxic payloads

Nakada T, Masuda T, Naito H, Yoshida M, Ashida S, Morita K, Miyazaki H, Kasuya Y, Ogitani Y, Yamaguchi J, Abe Y, Honda T

Trastuzumab conjugates consisting of exatecan derivatives were prepared and their biological activities and physicochemical properties were evaluated. The ADCs showed strong efficacy and a low aggregation rate. The exatecan derivatives were covalently connected via a peptidyl spacer (Gly-Gly-Phe-Gly), which is assumed to be stable in circulation, and were cleaved by lysosomal enzymes following ADC internalization into tumor tissue. These anti-HER2 ADCs exhibited a high potency, specifically against HER2-positive cancer cell lines in vitro. The ADCs, bearing exatecan derivatives which have more than two methylene chains, exhibited superior cytotoxicity. It was speculated that steric hindrance of the cleavable amide moiety could be involved in the drug release. The adequate alkyl lengths of exatecan derivatives (13, 14, 15) were from two to four in terms of aggregation rate. The ADC having a hydrophilic moiety showed good efficacy in a HER2-positive and Trastuzumab-resistant breast carcinoma cell model in mice.

Catalog	Product Name	CAS	Inquiry
BADC-00764	DBCO-PEG4-GGFG-DX8951

What is MC-GGFG-DX8951?

MC-GGFG-DX8951 is a cytotoxic linker conjugate designed for ADC applications. It features the DX8951 cytotoxin linked via a GGFG peptide sequence, enabling enzyme-responsive release within tumor cells. This construct is optimized for stability and targeted intracellular activity.

2/7/2019

We would like to know how MC-GGFG-DX8951 releases its payload.

The GGFG linker in MC-GGFG-DX8951 is cleaved by tumor-associated proteases, releasing the DX8951 cytotoxin specifically in cancer cells. This targeted cleavage reduces systemic toxicity while enhancing the cytotoxic effect at the site of action.

17/5/2022

Could you kindly inform us what research applications MC-GGFG-DX8951 supports?

MC-GGFG-DX8951 is employed in ADC development for both solid and hematologic tumors. Its peptide-linker design allows researchers to investigate enzyme-mediated payload release, pharmacokinetics, and in vitro/in vivo cytotoxicity profiles in preclinical studies.

22/9/2022

Good afternoon! Could you please explain what makes MC-GGFG-DX8951 suitable for ADCs?

MC-GGFG-DX8951 combines the potent DX8951 cytotoxin with a protease-cleavable GGFG linker, providing high stability in circulation and controlled release within target cells. Its design supports efficient ADC internalization and therapeutic efficacy.

15/7/2018

Good afternoon! Could you please advise if MC-GGFG-DX8951 can be conjugated to multiple antibody types?

Yes, MC-GGFG-DX8951 is compatible with various monoclonal antibodies and can be conjugated through standard cysteine or lysine residues. This enables ADC customization for different targets, payload ratios, and pharmacokinetic profiles.

5/9/2020

— Dr. Jason Carter, Senior Scientist (USA)

MC-GGFG-DX8951 purity and stability were excellent for reproducible ADC conjugation.

22/9/2022

— Dr. Olivia Bennett, ADC Chemist (UK)

Batch-to-batch reliability minimized variability in cytotoxicity assays.

5/9/2020

— Dr. James Carter, Senior Scientist (USA)

Working with BOC Sciences on MC-GGFG-DX8951 was seamless. The compound arrived with excellent purity, and the technical documentation was clear and compliant. This level of quality control truly gave our project a competitive edge.

15/7/2018

— Mr. Michael Carter, Senior Research Scientist (United Kingdom)

We were exploring a new conjugation strategy and needed a linker with a specific cleavable sequence. BOC Sciences' MC-GGFG-DX8951 was the perfect fit. The quality was outstanding, and the product consistency across batches was crucial for our preclinical studies. Highly recommend their ADC linker portfolio.

2/7/2019

— Mr. Daniel Kim, R&D Manager (United States)

Excellent quality and consistency. The MC-GGFG-DX8951 product was perfect for our preclinical screening and saved us valuable time.

— Dr. Helena Moore, Oncology Scientist (Ireland)

The MC-GGFG-DX8951 batch we ordered from BOC Sciences was exactly what our project required. High reproducibility and a clean data package allowed us to integrate it smoothly into our workflow.

17/5/2022