Name: DGN462
Brand: BOC Sciences
Rating: 5 (1 reviews)

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Synonyms

DGN-462; IMGN-779; IMGN779-linker; (5aS)-10-Methoxy-9-({3-[{2-[2-(2-methoxyethoxy)ethoxy]ethyl}(2-methyl-2-sulfanylpropyl)amino]-5-({[(5aS)-10-methoxy-12-oxo-5a,6,7,12-tetrahydro-5H-indolo[2,1-c][1,4]benzodiazepin-9-yl]oxy}methyl)benzyl}oxy)-5,5a-dihydro-12H-indolo[2,1-c][1,4]benzodiazepin-12-one; 6H-Indolo[2,1-c][1,4]benzodiazepin-6-one, 9-[[3-[[[(12aS)-12a,13-dihydro-8-methoxy-6-oxo-6H-indolo[2,1-c][1,4]benzodiazepin-9-yl]oxy]methyl]-5-[(2-mercapto-2-methylpropyl)[2-[2-(2-methoxyethoxy)ethoxy]ethyl]amino]phenyl]methoxy]-11,12,12a,13-tetrahydro-8-methoxy-, (12aS)-; (12aS)-9-[[3-[[[(12aS)-12a,13-Dihydro-8-methoxy-6-oxo-6H-indolo[2,1-c][1,4]benzodiazepin-9-yl]oxy]methyl]-5-[(2-mercapto-2-methylpropyl)[2-[2-(2-methoxyethoxy)ethoxy]ethyl]amino]phenyl]methoxy]-11,12,12a,13-tetrahydro-8-methoxy-6H-indolo[2,1-c][1,4]benzodiazepin-6-one

IUPAC Name

(12aS)-9-[[3-[[(12aS)-8-methoxy-6-oxo-11,12,12a,13-tetrahydroindolo[2,1-c][1,4]benzodiazepin-9-yl]oxymethyl]-5-[2-[2-(2-methoxyethoxy)ethoxy]ethyl-(2-methyl-2-sulfanylpropyl)amino]phenyl]methoxy]-8-methoxy-12a,13-dihydroindolo[2,1-c][1,4]benzodiazepin-6-one

Canonical SMILES

CC(C)(CN(CCOCCOCCOC)C1=CC(=CC(=C1)COC2=C(C=C3C(=C2)N=CC4CC5=CC=CC=C5N4C3=O)OC)COC6=C(C=C7C(=C6)NCC8CC9=CC=CC=C9N8C7=O)OC)S

InChI

InChI=1S/C53H59N5O9S/c1-53(2,68)33-56(14-15-64-18-19-65-17-16-61-3)38-21-34(31-66-49-27-43-41(25-47(49)62-4)51(59)57-39(29-54-43)23-36-10-6-8-12-45(36)57)20-35(22-38)32-67-50-28-44-42(26-48(50)63-5)52(60)58-40(30-55-44)24-37-11-7-9-13-46(37)58/h6-13,20-22,25-29,39-40,55,68H,14-19,23-24,30-33H2,1-5H3/t39-,40-/m0/s1

InChIKey

DOKWDOLZCMETIJ-ZAQUEYBZSA-N

Density

1.31±0.1 g/cm3

Solubility

Soluble in DMSO

Storage

Store at 2-8°C for short term (days to weeks) or -20°C for long term (months to years)

1.The novel CD19-targeting antibody-drug conjugate huB4-DGN462 shows improved anti-tumor activity compared to SAR3419 in CD19-positive lymphoma and leukemia models

Haematologica . 2019 Aug;104(8):1633-1639. doi: 10.3324/haematol.2018.211011. Epub 2019 Feb 7.

Antibody-drug conjugates (ADC) are a novel way to deliver potent cytotoxic compounds to cells expressing a specific antigen. Four ADC targeting CD19, including SAR3419 (coltuximab ravtansine), have entered clinical development. Here, we present huB4-DGN462, a novel ADC based on the SAR3419 anti-CD19 antibody linked via sulfo-SPDB to the potent DNA-alkylating agent DGN462. huB4-DGN462 had improved in vitro anti-proliferative and cytotoxic activity compared to SAR3419 across multiple B-cell lymphoma and human acute lymphoblastic leukemia cell lines. In vivo experiments using lymphoma xenografts models confirmed the in vitro data. The response of B-cell lymphoma lines to huB4-DGN462 was not correlated with CD19 expression, the presence of BCL2 or MYC translocations, TP53 inactivation or lymphoma histology. In conclusion, huB4-DGN462 is an attractive candidate for clinical investigation in patients with B-cell malignancies.