Linker Information

General Information of This Linker
Linker ID
LIN0QNMYF
Linker Name
WO2024239281A1, C158, Linker
Linker Type
Cathepsin-cleavable linker
Antibody-Linker Relation
Cleavable
Structure
Formula
C136H237N17O65
Isosmiles
C[C@@H](C(O)=O)NC([C@H](C(C)C)NC([C@H](CCC(NC(CCOCCC(NCCOCCOCCOCCOCCOCCOCCOCCOCCOCCC(NCCCC[C@@H](C(O)=O)NC(N[C@H](C(O)=O)CCC(O)=O)=O)=O)=O)(CCOCCC(NCCOCCOCCOCCOCCOCCOCCOCCOCCOCCC(NCCCC[C@@H](C(O)=O)NC(N[C@H](C(O)=O)CCC(O)=O)=O)=O)=O)CCOCCC(NCCOCCOCCOCCOCCOCCOCCOCCOCCOCCC(NCCCC[C@@H](C(O)=O)NC(N[C@H](C(O)=O)CCC(O)=O)=O)=O)=O)=O)NC(CCCN1C(C=CC1=O)=O)=O)=O)=O
InChI
InChI=1S/C136H237N17O65/c1-101(2)123(125(171)143-102(3)126(172)173)151-124(170)103(144-116(160)14-10-40-153-118(162)20-21-119(153)163)15-19-117(161)152-136(31-47-189-41-25-113(157)140-37-50-195-56-62-201-68-74-207-80-86-213-92-98-216-95-89-210-83-77-204-71-65-198-59-53-192-44-28-110(154)137-34-7-4-11-104(127(174)175)145-133(186)148-107(130(180)181)16-22-120(164)165,32-48-190-42-26-114(158)141-38-51-196-57-63-202-69-75-208-81-87-214-93-99-217-96-90-211-84-78-205-72-66-199-60-54-193-45-29-111(155)138-35-8-5-12-105(128(176)177)146-134(187)149-108(131(182)183)17-23-121(166)167)33-49-191-43-27-115(159)142-39-52-197-58-64-203-70-76-209-82-88-215-94-100-218-97-91-212-85-79-206-73-67-200-61-55-194-46-30-112(156)139-36-9-6-13-106(129(178)179)147-135(188)150-109(132(184)185)18-24-122(168)169/h20-21,101-109,123H,4-19,22-100H2,1-3H3,(H,137,154)(H,138,155)(H,139,156)(H,140,157)(H,141,158)(H,142,159)(H,143,171)(H,144,160)(H,151,170)(H,152,161)(H,164,165)(H,166,167)(H,168,169)(H,172,173)(H,174,175)(H,176,177)(H,178,179)(H,180,181)(H,182,183)(H,184,185)(H2,145,148,186)(H2,146,149,187)(H2,147,150,188)/t102-,103-,104-,105-,106-,107-,108-,109-,123-/m0/s1
InChIKey
XMZUSYJGSIDEAG-LSLLBXQVSA-N
Pharmaceutical Properties
Molecule Weight
3150.446
Polar area
1101.67
Complexity
.
xlogp Value
-4.0301
Heavy Count
218
Rot Bonds
159
Hbond acc
55
Hbond Donor
26
Each Antibody-drug Conjugate Related to This Linker
Full Information of The Activity Data of The ADC(s) Related to This Linker
wO2024239281A1 C158 [Investigative]
 ADC Info 
Revealed Based on the Cell Line Data
Click To Hide/Show 3 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal inhibitory Concentration (lC50)
0.019 nM
High Steap1 and PSMA expression (Steapl and PSMA +++)
Method Description
PC-3-4H7 cell is both Steap1and PSMA antigen high express cells. To run the assay,the cells (180 ul,6000cells)were added to each well in a 96-well plate and incubated for 24 hours at 37°C with 5%CO 2. Next,the cells were treated with test compounds (20ul)at various concentrations in appropriate cell culture medium (total volume,0.2 mL).The control wells contain cells and the medium but lack the test compounds.The plates were incubated for 120 hours at 37°C with 5%CO 2.MTT (5 mg/mL)was then added to the wells (20ul)and the plates were incubated for 1.5 hr at 37°C.The medium was carefully removed and DMSO (180ul)was added afterward.After it was shaken for 15min, the absorbance was measured at 490 nm and 570 nm with a reference filter of 620 nm.The inhibition% was calculated according to the following equation:inhibition%=[1- (assay-blank)/ (control-blank)]× 100.

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In Vitro Model Prostate carcinoma PC-3-4H7 cells Homo sapiens
Experiment 2 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal inhibitory Concentration (lC50)
0.025 nM
High Steap1 and PSMA expression (Steapl and PSMA +++)
Method Description
C4-2B is both Steap1 and PSMA antigen high express cells.To run the assay,the cells (180 ul,6000cells)were added to each well in a 96-well plate and incubated for 24 hours at 37°C with 5%CO 2. Next,the cells were treated with test compounds (20ul)at various concentrations in appropriate cell culture medium (total volume,0.2 mL).The control wells contain cells and the medium but lack the test compounds.The plates were incubated for 120 hours at 37°C with 5%CO 2.MTT (5 mg/mL)was then added to the wells (20ul)and the plates were incubated for 1.5 hr at 37°C.The medium was carefully removed and DMSO (180ul)was added afterward.After it was shaken for 15min, the absorbance was measured at 490 nm and 570 nm with a reference filter of 620 nm.The inhibition% was calculated according to the following equation:inhibition%=[1- (assay-blank)/ (control-blank)]× 100.

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In Vitro Model Prostate carcinoma C4-2B cells CVCL_4784
Experiment 3 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal inhibitory Concentration (lC50)
6.12 nM
Low Steap1 and PSMA expression (Steap1 and PSMA+)
Method Description
22RV1 is both Steapl and PSMA antigen low express cells.To run the assay,the cells (180 ul,6000cells)were added to each well in a 96-well plate and incubated for 24 hours at 37°C with 5%CO 2. Next,the cells were treated with test compounds (20ul)at various concentrations in appropriate cell culture medium (total volume,0.2 mL).The control wells contain cells and the medium but lack the test compounds.The plates were incubated for 120 hours at 37°C with 5%CO 2.MTT (5 mg/mL)was then added to the wells (20ul)and the plates were incubated for 1.5 hr at 37°C.The medium was carefully removed and DMSO (180ul)was added afterward.After it was shaken for 15min, the absorbance was measured at 490 nm and 570 nm with a reference filter of 620 nm.The inhibition% was calculated according to the following equation:inhibition%=[1- (assay-blank)/ (control-blank)]× 100.

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In Vitro Model Prostate carcinoma 22RV1 cells CVCL_1045
References
Ref 1 Targeted treatment of prostate cancers and other tumors by an antibody-drug conjugate