Name: MC-Sq-Cit-PAB-Dolastatin10
Brand: BOC Sciences
Rating: 5 (1 reviews)

Synonyms

MC Sq Cit PAB Dolastatin10

IUPAC Name

[4-[[(2S)-5-(carbamoylamino)-2-[[1-[5-(2,5-dioxopyrrol-1-yl)pentylcarbamoyl]cyclobutanecarbonyl]amino]pentanoyl]amino]phenyl]methyl-[(2S)-1-[[(2S)-1-[[(3R,4S,5S)-3-methoxy-1-[(2S)-2-[(1R,2R)-1-methoxy-2-methyl-3-oxo-3-[[(1S)-2-phenyl-1-(1,3-thiazol-2-yl)ethyl]amino]propyl]pyrrolidin-1-yl]-5-methyl-1-oxoheptan-4-yl]-methylamino]-3-methyl-1-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]-dimethylazanium

Canonical SMILES

C[N+]([C@H](C(N[C@H](C(N([C@@H]([C@@H](C)CC)[C@H](OC)CC(N1[C@H]([C@H](OC)[C@@H](C)C(N[C@H](C2=NC=CS2)CC3=CC=CC=C3)=O)CCC1)=O)C)=O)C(C)C)=O)C(C)C)(CC4=CC=C(NC([C@@H](NC(C5(C(NCCCCCN6C(C=CC6=O)=O)=O)CCC5)=O)CCCNC(N)=O)=O)C=C4)C

InChI

InChI=1S/C70H104N12O12S/c1-13-46(6)59(54(93-11)42-57(85)80-39-21-26-53(80)61(94-12)47(7)62(86)76-52(65-72-37-40-95-65)41-48-23-16-14-17-24-48)79(8)66(89)58(44(2)3)78-64(88)60(45(4)5)82(9,10)43-49-27-29-50(30-28-49)75-63(87)51(25-20-36-74-69(71)92)77-68(91)70(33-22-34-70)67(90)73-35-18-15-19-38-81-55(83)31-32-56(81)84/h14,16-17,23-24,27-32,37,40,44-47,51-54,58-61H,13,15,18-22,25-26,33-36,38-39,41-43H2,1-12H3,(H7-,71,73,74,75,76,77,78,86,87,88,90,91,92)/p+1/t46-,47+,51-,52-,53-,54+,58-,59-,60-,61+/m0/s1

Shipping

Room temperature

In Vitro

ADC1-2 (anti-CD22 10F4v3 LC K149C MC-Sq-Cit-PAB-Dolastatin 10) displays target-specific killing in WSU-DLCL2 human diffuse large B-cell lymphoma tumors with IC50 of 0.385 nM, and ADC1-1 (anti-Napi2b 10H1 11.4B LC K149C MC-Sq-Cit-PAB-Dolastatin 10) displays target-specific killing in human ovarian cancer IGROV-1 and OVCAR-3x2.1 with IC50s of 3.19 nM, 1.52 nM, respectively.

1.Quaternary amine compounds and antibody-drug conjugates thereof

FLYGARE, John A, et al.

This invention relates to antibody-drug conjugates represented by Formula (I) Ab- (L-D)p, Ab is an antibody; p is 1-8; L-D is a chemical moiety represented by the following formula -Str-(Pep)-Sp-D; Str is a stretcher unit covalently attached to Ab; Pep is a linker; D is anti-tumor agent represented by the following formula wherein R<20>and R<30>are each independently Ct-C6alkyl, and R<10>is a non-hydrogen substituent; or R<30>is C1-C6alkyl, and R<10>and R<20>together with the N form a substituted C3-C7heterocycloalkyl ring; or R<3>° is absent, and R<10>and R<20>together with the N form a substituted heteroaryl ring; Sp-D is a spacer moiety of fomula: This invention also relates to a method of treating cancer, use of antibody-drug conjugates of Formula (I) in therapy, and use of antibody-drug conjugates of Formula (I) in manufacturing a medicament for treating cancer. This invention also relates to method of preparing antibody-drug conjugates of Formula (I).

2.Targeted drug delivery through the traceless release of tertiary and heteroaryl amines from antibody-drug conjugates

Staben LR, et al.

The reversible attachment of a small-molecule drug to a carrier for targeted delivery can improve pharmacokinetics and the therapeutic index. Previous studies have reported the delivery of molecules that contain primary and secondary amines via an amide or carbamate bond; however, the ability to employ tertiary-amine-containing bioactive molecules has been elusive. Here we describe a bioreversible linkage based on a quaternary ammonium that can be used to connect a broad array of tertiary and heteroaryl amines to a carrier protein. Using a concise, protecting-group-free synthesis we demonstrate the chemoselective modification of 12 complex molecules that contain a range of reactive functional groups. We also show the utility of this connection with both protease-cleavable and reductively cleavable antibody-drug conjugates that were effective and stable in vitro and in vivo. Studies with a tertiary-amine-containing antibiotic show that the resulting antibody-antibiotic conjugate provided appropriate stability and release characteristics and led to an unexpected improvement in activity over the conjugates previously connected via a carbamate.