ML-Val-Cit-PAB

ML-Val-Cit-PAB - Names and Identifiers

Name	MC-Val-Cit-PAB
Synonyms	VCLINK MC-Val-it-PAB ML-Val-Cit-PAB MC-Val-Cit-PAB N-[6-(2,5-Dihydro-2,5-dioxo-1H-pyrrol-1-yl)-1-oxohexyl]-L-valyl-N5-(aminocarbonyl)-N-[4-(hydroxymethyl)phenyl]-L-ornithinamide L-OrnithinaMide, N-[6-(2,5-dihydro-2,5-dioxo-1H-pyrrol-1-yl)-1-oxohexyl]-L-valyl-N5-(aMinocarbonyl)-N-[4-(hydroxyMethyl)phenyl]- N-[(2S)-1-[[(2S)-5-(carbamoylamino)-1-[4-(hydroxymethyl)anilino]-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]-6-(2,5-dioxopyrrol-1-yl)hexanamide 6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-N-((S)-1-(((S)-1-((4-(hydroxymethyl)phenyl)amino)-1-oxo-5-ureidopentan-2-yl)amino)-3-methyl-1-oxobutan-2-yl)hexanamide
CAS	159857-80-4

ML-Val-Cit-PAB - Physico-chemical Properties

Molecular Formula	C28H40N6O7
Molar Mass	572.65
Density	1.276
Boling Point	931.6±65.0 °C(Predicted)
pKa	13.41±0.70(Predicted)
Storage Condition	under inert gas (nitrogen or Argon) at 2-8°C
Physical and Chemical Properties	Bioactive MC-Val-Cit-PAB, also known as MC-Val-Cit-PAB-OH, is a cathepsin cleavable ADC peptide linker used to prepare ADC conjugates (antibody-drug conjugates).
Use	Uses MC-Val-Cit-PAB intermediates are used as reagents for the preparation of antibody-drug conjugates, which are compounds that selectively deliver cytotoxic drugs to tumor-associated antigens.

ML-Val-Cit-PAB - Upstream Downstream Industry

Raw Materials	N-Succinimidyl 6-maleimidohexanoate 4-Aminobenzyl alcohol Val-cit-PAB-OH 6-Maleimidocaproic acid-PFP ester H-Cit-PABA 6-Maleimidocaproic acid FMOC-L-Valine L-Citrulline L-Ornithine, N5-(aMinocarbonyl)-N2-[N-[(9H-fluoren-9-ylMethoxy)carbonyl]-L-valyl]- FMOC-VAL-OSU FMoc-Val-Cit-PAB 6-Aminocaproic acid
Downstream Products	L-OrnithinaMide, N-[6-(2,5-dihydro-2,5-dioxo-1H-pyrrol-1-yl)-1-oxohexyl]-L-valyl-N5-(aMinocarbonyl)-N-[4-[[[(4-nitrophenoxy)carbonyl]oxy]Methyl]phenyl]-

ML-Val-Cit-PAB - Preparation solution concentration reference

	1mg	5mg	10mg
1 mM	1.746 ml	8.731 ml	17.463 ml
5 mM	0.349 ml	1.746 ml	3.493 ml
10 mM	0.175 ml	0.873 ml	1.746 ml
5 mM	0.035 ml	0.175 ml	0.349 ml

Last Update：2024-01-02 23:10:35

ML-Val-Cit-PAB - Uses and synthesis methods

ADC connector-Linker

Most ADC connectors currently undergoing clinical evaluation are divided into two categories: cuttable and non-cuttable. The cleavable linker relies on intracellular processes to release toxins, such as reduction of cytoplasm, exposure to acidic conditions in lysosomes, or cleavage of specific proteases within the cell. The non-cleavable linker requires proteolytic degradation of the antibody portion of the ADC to release cytotoxic molecules, which will retain the linker and the amino acids linked to the antibody. In addition, the choice of the linker is also affected by which cytotoxin is used, because each molecule has different chemical restrictions, and the drug structure is usually suitable for a specific linker.

MC-VAL-CIT-PAB (cas:159857-80-4) is an ADC connection bridge that can be cleaved by cathepsin and used to prepare antibody-drug conjugates. FDA-approved drugs such as brentuximab vedotin use the connection bridge.

Preparation

Synthesis of Compound 19(Fmoc-VC-PABA):

dissolve 1.5g compound 18(Fmoc-Val-Cit) in 14ml of dichloromethane and 7ml of methanol mixed solvent, add 4-aminobenzyl alcohol (445.2mg,3.62mmol), then add EEDQ(1.5g,6mmol), stir the reaction solution at room temperature overnight, add isopropyl ether to the residue after the solvent is concentrated and removed, stir and wash for 30min, filter the solid, add isopropyl ether to stir and wash again for 30min, and filter to obtain 1.5g of Fmoc-VC-PABA, 82% yield. M( 1)=602.6.

Compound 20(N-[6-(2, 5-dihydro-2, 5-dioxo-1H-pyrroli-1-yl)-1-oxohexyl]-L-valyl-N5-(carbamoyl)-N-[4-(hydroxymethyl) phenyl]-L-ornithamide) synthesis:

dissolve 2g of Fmoc-VC-PABA in 10mlDMF, add 2ml piperidine, stir at room temperature for 30min,TLC monitor the reaction completely and concentrate under reduced pressure with a high vacuum oil pump to obtain yellow solid, which can be directly used for the next reaction without purification.

Target

Cleavable

Last Update：2024-04-09 21:04:16