Payload Information

General Information of This Payload

Payload ID	PAY0AFEPS
Name	DGN462
Synonyms	DGN462; 1394079-41-4; SCHEMBL12523030; DGN 462; AKOS040732962; HY-101150; CS-0020917 Click to Show/Hide
Target(s)	Human Deoxyribonucleic acid (hDNA)			Target Info
Structure
Structure	3D MOL		2D MOL
Formula	C53H59N5O9S
Isosmiles	CC(C)(CN(CCOCCOCCOC)C1=CC(=CC(=C1)COC2=C(C=C3C(=C2)N=C[C@@H]4CC5=CC=CC=C5N4C3=O)OC)COC6=C(C=C7C(=C6)NC[C@@H]8CC9=CC=CC=C9N8C7=O)OC)S
PubChem CID	88930714
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
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
Pharmaceutical Properties	Molecule Weight	942.1	Polar area	134
	Complexity	1680	xlogp Value	6.6
	Heavy Count	68	Rot Bonds	20
	Hbond acc	13	Hbond Donor	2

Each Antibody-drug Conjugate Related to This Payload

Full Information of The Activity Data of The ADC(s) Related to This Payload

IMGN-779 [Clinical candidate]

ADC Info

Discovered Using Cell Line-derived Xenograft Model

Click To Hide/Show 2 Activity Data Related to This Level

Experiment 1 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 100.00% (Day 15)	Positive CD33 expression (CD33+++/++)
Method Description	EOL-1 tumor-bearing mice received a single intravenous bolus administration of vehicle, IMGN779, or Ab-DGN462, with each conjugate molecule dosed at approximately 1.5 mg/kg ADC by antibody concentration (i.e., 10 or 30 ug/kg linked IGN).
In Vivo Model	EOL-1 CDX model
In Vitro Model	Chronic eosinophilic leukemia	EoL-1 cells		CVCL_0258
Experiment 2 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 100.00% (Day 30)	Positive CD33 expression (CD33+++/++)
Method Description	IMGN779 (0.5 mg/kg, a single dose) induces efficient tumor cell killing in cell line-derived models of MV4-11 cells with CD33 expression with high expression.
In Vivo Model	MV4-11 CDX model
In Vitro Model	Childhood acute monocytic leukemia	MV4-11 cells		CVCL_0064

References

Ref 1	IMGN779, a Novel CD33-Targeting Antibody-Drug Conjugate with DNA-Alkylating Activity, Exhibits Potent Antitumor Activity in Models of AML. Mol Cancer Ther. 2018 Jun;17(6):1271-1279. doi: 10.1158/1535-7163.MCT-17-1077. Epub 2018 Mar 27.