Linker Information

General Information of This Linker

Linker ID	LIN0KDRVI
Linker Name	Mal-PEG8-Val-Ala
Linker Type	Cathepsin-cleavable linker
Antibody-Linker Relation	Cleavable
Structure
Structure	3D MOL		2D MOL
Formula	C34H58N4O15
Isosmiles	CC(NC(=O)C(NC(=O)CCOCCOCCOCCOCCOCCOCCOCCOCCNC(=O)CCN1C(=O)C=CC1=O)C(C)C)C(=O)O
InChI	InChI=1S/C34H58N4O15/c1-26(2)32(33(43)36-27(3)34(44)45)37-29(40)7-10-46-12-14-48-16-18-50-20-22-52-24-25-53-23-21-51-19-17-49-15-13-47-11-8-35-28(39)6-9-38-30(41)4-5-31(38)42/h4-5,26-27,32H,6-25H2,1-3H3,(H,35,39)(H,36,43)(H,37,40)(H,44,45)
InChIKey	GITGYODHQZKNBP-UHFFFAOYSA-N
Pharmaceutical Properties	Molecule Weight	762.851	Polar area	235.82
	Complexity	53	xlogp Value	-1.3293
	Heavy Count	53	Rot Bonds	35
	Hbond acc	14	Hbond Donor	4

Each Antibody-drug Conjugate Related to This Linker

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

AZD-8205 [Phase 1/2]

ADC Info

Identified from the Human Clinical Data

Click To Hide/Show 1 Activity Data Related to This Level

Experiment 1 Reporting the Activity Date of This ADC				[1]
Patients Enrolled	Patients 18 years old with cholangiocarcinoma, breast, ovarian or endometrial cancers and ECOG PS 0-1.
*Related Clinical Trial*
NCT Number	NCT05123482	Clinical Status	Phase 1/2
Clinical Description	A phase 1/2a multi-center, open-label master protocol to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary antitumor activity of AZD8205 in participants with advanced or metastatic solid malignancies.

Discovered Using Patient-derived Xenograft Model

Click To Hide/Show 1 Activity Data Related to This Level

Experiment 1 Reporting the Activity Date of This ADC				[2]
Efficacy Data	Objective Response Rate (ORR)	69.00%	Positive VTCN1 expression (VTCN1+++/++)
Method Description	In the study of 26 PDX tumors,single administration of 3.5 mg/kg AZD8205 to determine the ORR,according to modified RECIST criteria,which correlated with homologous recombination repair (HRR) deficiency (HRD) and elevated levels of B7-H4 in HRR-proficient models.
In Vivo Model	Multiple tumor PDX model

References

Ref 1	First in human dose-escalation trial with the c-MET targeting antibody-drug conjugate BYON3521. Cancer Res (2023) 83 (8_Supplement): CT185.
Ref 2	Design and Preclinical Evaluation of a Novel B7-H4-Directed Antibody-Drug Conjugate, AZD8205, Alone and in Combination with the PARP1-Selective Inhibitor AZD5305. Clin Cancer Res. 2023 Mar 14;29(6):1086-1101.