Satralizumab Linker

Satralizumab Linker Property

form 

Solid

color 

White to off-white

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Danger

Hazard statements

H341Suspected of causing genetic defects

H360May damage fertility or the unborn child

H373May cause damage to organs through prolonged or repeated exposure

Precautionary statements

P201Obtain special instructions before use.

P202Do not handle until all safety precautions have been read and understood.

P260Do not breathe dust/fume/gas/mist/vapours/spray.

P281Use personal protective equipment as required.

P308+P313IF exposed or concerned: Get medical advice/attention.

P314Get medical advice/attention if you feel unwell.

P405Store locked up.

P501Dispose of contents/container to..…

Satralizumab Linker Chemical Properties,Usage,Production

Uses

Sacituzumab govitecan (IMMU-132) is an antibody-drug conjugate (ADC) targeting Trop-2 for delivery of SN-38. Sacituzumab govitecan shows anticancer activity[1].

Mechanism of action

Through the targeting effect of antibodies, Sacituzumab Govitecan delivers SN-38 directly to tumor cells expressing Trop-2. SN-38 is a topoisomerase I inhibitor that can cause DNA double-strand breaks, thereby inhibiting the replication and division of tumor cells.

Synthesis

The lysine derivative 321 was coupled with p-aminobenzyl alcohol, followed by the removal of the carbamate protecting group to afford the α-aminoamide 323. This amine was then coupled with the commercial α,ο-hydrazide 325 to afford the benzyl alcohol 323 in excellent yield. The benzyl alcohol 323 was then reacted with the chloroformate 320 under mild alkaline conditions to afford the carbonate 326. The removal of the silyl ether protecting group under acidic conditions, followed by click cyclization with the alkyne 327 and the removal of the trityl protection in 326, ultimately afforded CL2A-SN-38 (328) in excellent yield. The disulfide bonds of the Trop-2 antibody were first cleaved using tris(2-carboxyethyl)phosphine (TCEP) as a reducing agent. The cleaved disulfide Trop-2 antibody was then reacted with CL2A-SN-38, followed by a clearance reaction using N-ethylmaleimide. This series of reactions resulted in a Michael addition reaction on the reduced antibody, which proceeded at a stoichiometric ratio of approximately 7.6. Through these steps, Sacituzumab Govitecan was finally obtained.

in vivo

References

[1] Cardillo TM, et al. Sacituzumab Govitecan (IMMU-132), an Anti-Trop-2/SN-38 Antibody-Drug Conjugate: Characterization and Efficacy in Pancreatic, Gastric, and Other Cancers. Bioconjug Chem. 2015 May 20;26(5):919-31. DOI:10.1021/acs.bioconjchem.5b00223
[2] Goldenberg DM, Cardillo TM, Govindan SV, Rossi EA, Sharkey RM. Trop-2 is a novel target for solid cancer therapy with sacituzumab govitecan (IMMU-132), an antibody-drug conjugate (ADC) [published correction appears in Oncotarget. 2020 Mar 10;11(10):942]. Oncotarget. 2015;6(26):22496-22512. DOI:10.18632/oncotarget.4318
[3] Cardillo TM, et al., Sacituzumab Govitecan (IMMU-132), an Anti-Trop-2/SN-38 Antibody-Drug Conjugate: Characterization and Efficacy in Pancreatic, Gastric, and Other Cancers. Bioconjug Chem. 2015 May 20;26(5):919-31. DOI:10.1021/acs.bioconjchem.5b00223