Linker Information

General Information of This Linker
Linker ID
LIN0RJLTB
Linker Name
HIPS-4AP
Antibody-Linker Relation
Uncleavable
Structure
Formula
C30H45N5O8
Isosmiles
CNN(C)Cc1cc2ccccc2n1CCC(=O)N1CCC(N(CCOCCOCCC(=O)O)C(=O)CCC(=O)O)CC1
InChI
InChI=1S/C30H45N5O8/c1-31-32(2)22-25-21-23-5-3-4-6-26(23)34(25)15-11-27(36)33-13-9-24(10-14-33)35(28(37)7-8-29(38)39)16-18-43-20-19-42-17-12-30(40)41/h3-6,21,24,31H,7-20,22H2,1-2H3,(H,38,39)(H,40,41)
InChIKey
HCTLBFZUSUCBMW-UHFFFAOYSA-N
Pharmaceutical Properties
Molecule Weight
603.717
Polar area
153.88
Complexity
603.3268134
xlogp Value
1.7899
Heavy Count
43
Rot Bonds
19
Hbond acc
9
Hbond Donor
3
Each Antibody-drug Conjugate Related to This Linker
Full Information of The Activity Data of The ADC(s) Related to This Linker
TRPH-222 [Phase 1 (Terminated)]
 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]
Efficacy Data Objective Response Rate (ORR)
22.70% (all)
Patients Enrolled
Patients with diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), and marginal zone lymphoma (MZL) were enrolled. Patients had received a median of 4 prior systemic therapy.
Administration Dosage
TRPH-222 was administered IV 0.60 to 5.60 mg/kg once every 3 weeks.
Related Clinical Trial
NCT Number NCT03682796  Clinical Status Phase 1
Clinical Description
Phase 1, multicenter, open-label study of the antibody-drug conjugate TRPH-222 in subjects with relapsed and/or refractory B-cell lymphoma.
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 7 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [2]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 51.00% (Day 28) Positive CD22 expression (CD22+++/++)
Method Description
In WSU-DLCL2 xenografts once weekly intravenous (IV) dosing with 1 mg/kg TRPH-222.
In Vivo Model Non-Hodgkin's lymphoma CDX model
In Vitro Model Diffuse large B-cell lymphoma WSU-DLCL2 cells CVCL_1902
Experiment 2 Reporting the Activity Date of This ADC [3]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 87.00% (Day 28) Positive CD22 expression (CD22+++/++)
Method Description
In Granta-519 xenografts,trph-222 was dosed at 10 mg/kg once weekly intravenous (IV).
In Vivo Model Mantle cell lymphoma CDX model
In Vitro Model Mantle cell lymphoma Granta-519 cells CVCL_1818
Experiment 3 Reporting the Activity Date of This ADC [3]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 91.00% (Day 28) Positive CD22 expression (CD22+++/++)
Method Description
In SU-DHL-2 xenografts,trph-222 was dosed at 10 mg/kg once weekly intravenous (IV).
In Vivo Model Diffuse large B cell lymphoma CDX model
In Vitro Model Diffuse large B-cell lymphoma SU-DHL-2 cells CVCL_9550
Experiment 4 Reporting the Activity Date of This ADC [3]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 100.00% (Day 28) Positive CD22 expression (CD22+++/++)
Method Description
In SU-DHL-4 xenografts,trph-222 was dosed at 10 mg/kg once weekly intravenous (IV).
In Vivo Model Diffuse large B cell lymphoma CDX model
In Vitro Model Diffuse large B-cell lymphoma SU-DHL-4 cells CVCL_0539
Experiment 5 Reporting the Activity Date of This ADC [3]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 100.00% (Day 28) Positive CD22 expression (CD22+++/++)
Method Description
In WSU-DLCL2 xenografts once every three-week intravenous (IV) dosing with 10 mg/kg TRPH-222.
In Vivo Model Non-Hodgkin's lymphoma CDX model
In Vitro Model Diffuse large B-cell lymphoma WSU-DLCL2 cells CVCL_1902
Experiment 6 Reporting the Activity Date of This ADC [3]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 100.00% (Day 28) Positive CD22 expression (CD22+++/++)
Method Description
In WSU-DLCL2 xenografts once weekly intravenous (IV) dosing with 10 mg/kg TRPH-222.
In Vivo Model Non-Hodgkin's lymphoma CDX model
In Vitro Model Diffuse large B-cell lymphoma WSU-DLCL2 cells CVCL_1902
Experiment 7 Reporting the Activity Date of This ADC [3]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 100.00% (Day 28) Positive CD22 expression (CD22+++/++)
Method Description
In WSU-DLCL2 xenografts once weekly intravenous (IV) dosing with 3 mg/kg TRPH-222.
In Vivo Model Non-Hodgkin's lymphoma CDX model
In Vitro Model Diffuse large B-cell lymphoma WSU-DLCL2 cells CVCL_1902
References
Ref 1 First-in-Human Phase I Study of ABBV-085, an Antibody-Drug Conjugate Targeting LRRC15, in Sarcomas and Other Advanced Solid Tumors. Clin Cancer Res. 2021 Jul 1;27(13):3556-3566. doi: 10.1158/1078-0432.CCR-20-4513.
Ref 2 Trph-222, a Novel Anti-CD22 Antibody Drug Conjugate (ADC), Has Signficant Anti-Tumor Activity in NHL Xenografts and Is Well Tolerated in Non-Human Primates. Blood. 2017 Dec 8;130 (Suppl_1) : 4105.
Ref 3 TRPH-222, a novel anti-CD22 antibody drug conjugate (ADC), has significant anti-tumor activity in NHL xenografts and reduces B cells in monkeys.