Name: CL2 Linker
Brand: BOC Sciences
Rating: 5 (1 reviews)

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IUPAC Name

Canonical SMILES

OCC(COC(N(C)CCN(C)C(OCC(C=C1)=CC=C1NC([C@H](CCCCNC(OC(C)(C)C)=O)NC([C@@H](NC(CCOCCOCCOCCOCCOCCOCCOCCOCCN2C=C(CNC(CCCCCN3C(C=CC3=O)=O)=O)N=N2)=O)CC4=CC=CC=C4)=O)=O)=O)=O)=O

InChI

InChI=1S/C68H103N11O22/c1-68(2,3)101-65(88)69-25-12-11-16-57(63(86)71-54-20-18-53(19-21-54)50-99-66(89)76(4)27-28-77(5)67(90)100-51-56(81)49-80)73-64(87)58(46-52-14-8-6-9-15-52)72-60(83)24-30-91-32-34-93-36-38-95-40-42-97-44-45-98-43-41-96-39-37-94-35-33-92-31-29-78-48-55(74-75-78)47-70-59(82)17-10-7-13-26-79-61(84)22-23-62(79)85/h6,8-9,14-15,18-23,48,57-58,80H,7,10-13,16-17,24-47,49-51H2,1-5H3,(H,69,88)(H,70,82)(H,71,86)(H,72,83)(H,73,87)/t57-,58-/m0/s1

InChIKey

BGFZCTPREVDQQQ-YQOHNZFASA-N

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CL2 linker is a versatile chemical compound used in bioconjugation and molecular biology applications. Here are some key applications of CL2 linker:

Antibody-Drug Conjugates (ADCs): The CL2 linker is widely used in the development of antibody-drug conjugates, where it connects a cytotoxic drug to an antibody. This linker ensures stable attachment during circulation and releases the drug in a controlled manner upon reaching the target cells. This targeted delivery enhances the therapeutic efficacy while minimizing off-target effects.

Protein-Protein Interactions: CL2 linkers are used to study protein-protein interactions by covalently linking two proteins of interest. By maintaining the spatial orientation and functional integrity of the proteins, researchers can investigate the dynamics and mechanics of their interactions. This is crucial for understanding cellular processes and developing new therapeutic strategies.

Peptide Synthesis: In peptide synthesis, CL2 linkers serve as spacers or connectors between different peptide sequences. They facilitate the assembly of complex peptides and proteins with desired functionalities. These linkers help in maintaining the structural and functional integrity of the synthesized peptides, ensuring they perform their intended biological roles.

Biomolecule Immobilization: CL2 linkers are employed to immobilize biomolecules, such as enzymes or antibodies, onto solid supports for various analytical and diagnostic applications. This immobilization enhances the stability and reusability of the biomolecules, making it easier to conduct repetitive assays. Their use is crucial in creating biosensors and other bioanalytical devices.

1.Antibody conjugates of 7-ethyl-10-hydroxycamptothecin (SN-38) for targeted cancer chemotherapy

Moon SJ, Govindan SV, Cardillo TM, D'Souza CA, Hansen HJ, Goldenberg DM

CPT-11 is a clinically used cancer drug, and it is a prodrug of the potent topoisomerase I inhibitor, SN-38 (7-ethyl-10-hydroxycamptothecin). To bypass the need for the in vivo conversion of CPT-11 and increase the therapeutic index, bifunctional derivatives of SN-38 were prepared for use in antibody-based targeted therapy of cancer. The general synthetic scheme incorporated an acetylene-azide click cycloaddition step in the design, a short polyethylene glycol spacer for aqueous solubility, and a maleimide group for conjugation. Conjugates of a humanized anti-CEACAM5 monoclonal antibody, hMN-14, prepared using these SN-38 derivatives were evaluated in vitro for stability in buffer and human serum and for antigen-binding and cytotoxicity in a human colon adenocarcinoma cell line. Conjugates of hMN-14 and SN-38 derivatives 16 and 17 were found promising for further development.

2.Humanized anti-Trop-2 IgG-SN-38 conjugate for effective treatment of diverse epithelial cancers: preclinical studies in human cancer xenograft models and monkeys

Cardillo TM, Govindan SV, Sharkey RM, Trisal P, Goldenberg DM

PURPOSE:Evaluate the efficacy of an SN-38-anti-Trop-2 antibody-drug conjugate (ADC) against several human solid tumor types, and to assess its tolerability in mice and monkeys, the latter with tissue cross-reactivity to hRS7 similar to humans.EXPERIMENTAL DESIGN:Two SN-38 derivatives, CL2-SN-38 and CL2A-SN-38, were conjugated to the anti-Trop-2-humanized antibody, hRS7. The immunoconjugates were characterized in vitro for stability, binding, and cytotoxicity. Efficacy was tested in five different human solid tumor-xenograft models that expressed Trop-2 antigen. Toxicity was assessed in mice and in Cynomolgus monkeys.RESULTS:The hRS7 conjugates of the two SN-38 derivatives were equivalent in drug substitution (∼ 6), cell binding (K(d) ∼ 1.2 nmol/L), cytotoxicity (IC(50) ∼ 2.2 nmol/L), and serum stability in vitro (t/(½) ∼ 20 hours). Exposure of cells to the ADC demonstrated signaling pathways leading to PARP cleavage, but differences versus free SN-38 in p53 and p21 upregulation were noted. Significant antitumor effects were produced by hRS7-SN-38 at nontoxic doses in mice bearing Calu-3 (P ≤ 0.05), Capan-1 (P < 0.018), BxPC-3 (P < 0.005), and COLO 205 tumors (P < 0.033) when compared to nontargeting control ADCs. Mice tolerated a dose of 2 × 12 mg/kg (SN-38 equivalents) with only short-lived elevations in ALT and AST liver enzyme levels. Cynomolgus monkeys infused with 2 × 0.96 mg/kg exhibited only transient decreases in blood counts, although, importantly, the values did not fall below normal ranges.CONCLUSIONS:The anti-Trop-2 hRS7-CL2A-SN-38 ADC provides significant and specific antitumor effects against a range of human solid tumor types. It is well tolerated in monkeys, with tissue Trop-2 expression similar to humans, at clinically relevant doses, and warrants clinical investigation.