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943630

Mc-Val-Cit-PAB-Cl

≥95%

Synonym(s):

N-((S)-1-(((S)-1-((4-(Chloromethyl)phenyl)amino]-1-oxo-5-ureidopentan-2-yl)amino]-3-methyl-1-oxobutan-2-yl)-6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanamide, N-[(1S)-1-[[(1S)-4-(carbamoylamino)-1-[[4-(chloromethyl)phenyl]-carbamoyl]butyl]carbamoyl]-2-methylpropyl]-6-(2,5-dioxopyrrol-1- yl)hexanamide, N-[6-(2,5-Dihydro-2,5-dioxo-1H-pyrrol-1-yl)-1-oxohexyl]-L-valyl-N5-(aminocarbonyl)-N-[4-(chloromethyl)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-(chloromethyl)phenyl], Mc-Val-Cit-PAB-Cl, Cleavable ADC Linker with Val-Cit / PAB Spacer

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About This Item

Empirical Formula (Hill Notation):
C28H39ClN6O6
CAS Number:
1639351-92-0
Molecular Weight:
591.10
MDL number:
MFCD32201033
NACRES:
NA.21
Assay:
≥95%
Form:
solid
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Quality Segment

100

assay

≥95%

form

solid

storage condition

protect from light

color

off-white to pale yellow

storage temp.

−20°C

SMILES string

O=C(N)NCCCC(NC(=O)C(NC(=O)CCCCCN1C(=O)C=CC1=O)C(C)C)C(=O)NC2=CC=C(C=C2)CCl

InChI

1S/C28H39ClN6O6/c1-18(2)25(34-22(36)8-4-3-5-16-35-23(37)13-14-24(35)38)27(40)33-21(7-6-15-31-28(30)41)26(39)32-20-11-9-19(17-29)10-12-20/h9-14,18,21,25H,3-8,15-17H2,1-2H3,(H,32,39)(H,33,40)(H,34,36)(H3,30,31,41)/t21-,25-/m0/s1

InChI key

TUMQZNBKSWFFAZ-OFVILXPXSA-N

General description

Mc-Val-Cit-PAB-Cl is a protease-cleavable linker used in antibody-drug conjugates (ADCs). Specifically, it contains the Val-Cit (valine-citrulline) dipeptide motif, which is cleaved by cathepsin proteases in the lysosome, coupled with a PAB (para-aminobenzyl) carbamate (PAB-Cl indicates PAB with a chloromethyl group) self-immolative spacer, and a terminal chloromethyl phenyl group for conjugation. It’s designed to link the cytotoxic payload (e.g. MMAE) to an antibody, forming an ADC such as MC-VC-PABC-MMAE.

Application

  • Antibody-Drug Conjugates (ADCs): A linker component for ADCs, particularly with MMAE (Monomethyl auristatin E), forming ADCs with cytotoxic activity.
  • Cancer research: Used in preclinical ADC constructs against tumor cell lines. For example, anti-CD22-MC-VC-PABC-MMAE showing IC₅₀s in BJAB, WSU cell lines.
  • Bioconjugation chemistry: Useful as a linker for conjugating antibodies with small molecule payloads.

Features and Benefits

  • Cleavable by proteases (Val-Cit motif): Ensures drug release specifically in the target cell lysosome environment.
  • Self-immolative spacer (PAB-Cl): After proteolytic cleavage, the PAB spacer facilitates release of free drug.
  • Chloromethyl phenyl group: Provides a handle for stable conjugation chemistry to antibodies.

Other Notes

  • Protease cleavage: Val-Cit portion is recognized and cleaved by cathepsin enzymes (often cathepsin B) in lysosomes. Amide bond formation: The linker has amide bonds; payloads or antibodies typically conjugate via amine or thiol reactive groups.
  • Self-immolative release: After proteolytic trigger, the PAB spacer undergoes spontaneous decomposition to release the drug moiety.
  • Sensitivity: Must avoid conditions that degrade the Val-Cit or PAB moieties prematurely (e.g., perhaps strong acids, high temperatures, non-compatible buffers).

pictograms

Exclamation mark
GHS07

signalword

Warning

hcodes

H317

Hazard Classifications

Skin Sens. 1B

Storage Class

11 - Combustible Solids

flash_point_f

Not applicable

flash_point_c

Not applicable

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