Linker Information

General Information of This Linker
Linker ID
LIN0ZEYRW
Linker Name
Pyrimidine-CL2A-carbonate
Linker Type
pH-sensitive linker
Antibody-Linker Relation
Cleavable
Structure
Formula
C47H72N10O14
Isosmiles
NCCCCC(NC(=O)COCC(=O)NCCOCCOCCOCCOCCOCCOCCOCCOCCn1cc(NC(=O)CCCC#Cc2cncnc2)nn1)C(=O)Nc1ccc(CO)cc1
InChI
InChI=1S/C47H72N10O14/c48-13-5-4-7-42(47(62)52-41-11-9-39(35-58)10-12-41)53-46(61)37-71-36-45(60)51-14-16-63-18-20-65-22-24-67-26-28-69-30-31-70-29-27-68-25-23-66-21-19-64-17-15-57-34-43(55-56-57)54-44(59)8-3-1-2-6-40-32-49-38-50-33-40/h9-12,32-34,38,42,58H,1,3-5,7-8,13-31,35-37,48H2,(H,51,60)(H,52,62)(H,53,61)(H,54,59)
InChIKey
JUDMUQGUSXPCEE-UHFFFAOYSA-N
Pharmaceutical Properties
Molecule Weight
1001.149
Polar area
302.21
Complexity
71
xlogp Value
0.239
Heavy Count
71
Rot Bonds
43
Hbond acc
20
Hbond Donor
6
Each Antibody-drug Conjugate Related to This Linker
Full Information of The Activity Data of The ADC(s) Related to This Linker
SKB-264 [Phase 3]
 ADC Info 
Identified from the Human Clinical Data
Click To Hide/Show 5 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [1]
Related Clinical Trial
NCT Number NCT05347134  Clinical Status Phase 3
Clinical Description
A randomized, controlled, open-label, multi-center phase 3 clinical trial of SKB264 for injection versus investigator selected regimens in patients with unresectable locally advanced, recurrent or metastatic triple-negative breast cancer who have failed second-line or above prior standard of care.
Experiment 2 Reporting the Activity Date of This ADC [2]
Related Clinical Trial
NCT Number NCT05642780  Clinical Status Phase 2
Clinical Description
Amulticenter, open-label, phase 2, basket study to evaluate the efficacy and safety of SKB264 in combination with pembrolizumab in subjects with selected solid tumors.
Experiment 3 Reporting the Activity Date of This ADC [3]
Related Clinical Trial
NCT Number NCT05631262  Clinical Status Phase 2
Clinical Description
A multicenter, open-label, phase 2 study to evaluate the efficacy and safety of SKB264 monotherapy in selected subjects with advanced solid tumors.
Experiment 4 Reporting the Activity Date of This ADC [4]
Related Clinical Trial
NCT Number NCT05445908  Clinical Status Phase 2
Clinical Description
A phase 2 clinical study of SKB264 with/without KL-A167 in patients with unresectable locally advanced, recurrent or metastatic triple-negative breast cancer (TNBC) who have not received prior systemic therapy.
Experiment 5 Reporting the Activity Date of This ADC [5]
Related Clinical Trial
NCT Number NCT05351788  Clinical Status Phase 2
Clinical Description
A phase 2 clinical study of combination therapy of SKB264 in patients with advanced or metastatic non-small cell lung cancer.
Discovered Using Patient-derived Xenograft Model
Click To Hide/Show 15 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [6]
Efficacy Data Tumor Growth Inhibition value (TGI) < 30.00% (Day 21) Negative TROP2 expression (TROP2-)
Method Description
The tumor-bearing mice were treated with SKB264 via i.v. injection at doses of 1 mg/kg for gastric cancer PDX models twice a week for six times.
In Vivo Model Gastric cancer PDX model (PDX: A11068)
Experiment 2 Reporting the Activity Date of This ADC [6]
Efficacy Data Tumor Growth Inhibition value (TGI) < 30.00% (Day 21) Negative TROP2 expression (TROP2-)
Method Description
The tumor-bearing mice were treated with SKB264 via i.v. injection at doses of 3 mg/kg for gastric cancer PDX models twice a week for six times.
In Vivo Model Gastric cancer PDX model (PDX: A11068)
Experiment 3 Reporting the Activity Date of This ADC [6]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 38.40% (Day 21) Moderate TROP2 expression (TROP2++)
Method Description
The tumor-bearing mice were treated with SKB264 via i.v. injection at doses of 1 mg/kg for gastric cancer PDX models twice a week for six times.
In Vivo Model Gastric cancer PDX model (PDX: A11068)
Experiment 4 Reporting the Activity Date of This ADC [6]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 42.90% (Day 21) Low TROP2 expression (TROP2+)
Method Description
The tumor-bearing mice were treated with SKB264 via i.v. injection at doses of 1 mg/kg for gastric cancer PDX models twice a week for six times.
In Vivo Model Gastric cancer PDX models (PDX: 0501116)
Experiment 5 Reporting the Activity Date of This ADC [6]
Efficacy Data Tumor Growth Inhibition value (TGI)
44.00% (Day 24)
High TROP2 expression (TROP2+++)
Method Description
The tumor-bearing mice were treated with SKB264 via i.v. injection at doses of 0.5 mg/kg for BR1282 PDX models twice a week for six times.
In Vivo Model Breast cancer PDX model (PDX: BR1282)
Experiment 6 Reporting the Activity Date of This ADC [6]
Efficacy Data Tumor Growth Inhibition value (TGI) < 50.00% (Day 21) Negative TROP2 expression (TROP2-)
Method Description
The tumor-bearing mice were treated with SKB264 via i.v. injection at doses of 10 mg/kg for gastric cancer PDX models twice a week for six times.
In Vivo Model Gastric cancer PDX model (PDX: A11068)
Experiment 7 Reporting the Activity Date of This ADC [6]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 66.70% (Day 21) High TROP2 expression (TROP2+++)
Method Description
The tumor-bearing mice were treated with SKB264 via i.v. injection at doses of 1 mg/kg for gastric cancer PDX models twice a week for six times.
In Vivo Model Gastric cancer PDX models (PDX: 406022)
Experiment 8 Reporting the Activity Date of This ADC [6]
Efficacy Data Tumor Growth Inhibition value (TGI)
92.60% (Day 24)
High TROP2 expression (TROP2+++)
Method Description
The tumor-bearing mice were treated with SKB264 via i.v. injection at doses of 1.5 mg/kg for BR1282 PDX models twice a week for six times.
In Vivo Model Breast cancer PDX model (PDX: BR1282)
Experiment 9 Reporting the Activity Date of This ADC [6]
Efficacy Data Tumor Growth Inhibition value (TGI)
100.00% (Day 21)
High TROP2 expression (TROP2+++)
Method Description
The tumor-bearing mice were treated with SKB264 via i.v. injection at doses of 10 mg/kg for gastric cancer PDX models twice a week for six times.
In Vivo Model Gastric cancer PDX models (PDX: 406022)
Experiment 10 Reporting the Activity Date of This ADC [6]
Efficacy Data Tumor Growth Inhibition value (TGI)
100.00% (Day 21)
Moderate TROP2 expression (TROP2++)
Method Description
The tumor-bearing mice were treated with SKB264 via i.v. injection at doses of 10 mg/kg for gastric cancer PDX models twice a week for six times.
In Vivo Model Gastric cancer PDX model (PDX: A11068)
Experiment 11 Reporting the Activity Date of This ADC [6]
Efficacy Data Tumor Growth Inhibition value (TGI)
100.00% (Day 21)
Low TROP2 expression (TROP2+)
Method Description
The tumor-bearing mice were treated with SKB264 via i.v. injection at doses of 10 mg/kg for gastric cancer PDX models twice a week for six times.
In Vivo Model Gastric cancer PDX models (PDX: 0501116)
Experiment 12 Reporting the Activity Date of This ADC [6]
Efficacy Data Tumor Growth Inhibition value (TGI)
100.00% (Day 21)
High TROP2 expression (TROP2+++)
Method Description
The tumor-bearing mice were treated with SKB264 via i.v. injection at doses of 3 mg/kg for gastric cancer PDX models twice a week for six times.
In Vivo Model Gastric cancer PDX models (PDX: 406022)
Experiment 13 Reporting the Activity Date of This ADC [6]
Efficacy Data Tumor Growth Inhibition value (TGI)
100.00% (Day 21)
Moderate TROP2 expression (TROP2++)
Method Description
The tumor-bearing mice were treated with SKB264 via i.v. injection at doses of 3 mg/kg for gastric cancer PDX models twice a week for six times.
In Vivo Model Gastric cancer PDX model (PDX: A11068)
Experiment 14 Reporting the Activity Date of This ADC [6]
Efficacy Data Tumor Growth Inhibition value (TGI)
100.00% (Day 21)
Low TROP2 expression (TROP2+)
Method Description
The tumor-bearing mice were treated with SKB264 via i.v. injection at doses of 3 mg/kg for gastric cancer PDX models twice a week for six times.
In Vivo Model Gastric cancer PDX models (PDX: 0501116)
Experiment 15 Reporting the Activity Date of This ADC [6]
Efficacy Data Tumor Growth Inhibition value (TGI)
100.00% (Day 24)
High TROP2 expression (TROP2+++)
Method Description
The tumor-bearing mice were treated with SKB264 via i.v. injection at doses of 5 mg/kg for BR1282 PDX models twice a week for six times.
In Vivo Model Breast cancer PDX model (PDX: BR1282)
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 6 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [6]
Efficacy Data Tumor Growth Inhibition value (TGI)
51.20% (Day 24)
High TROP2 expression (TROP2+++)
Method Description
When the average tumor volume reached about 120 mm3, mice were randomized into five groups (n = 8) and subsequently administered by intravenous (i.v.) injection with the testing item twice a week for six times. SKB264 treatments were performed at doses of 3 mg/kg in the NCI-N87.
In Vitro Model Gastric tubular adenocarcinoma NCI-N87 cells CVCL_1603
Experiment 2 Reporting the Activity Date of This ADC [6]
Efficacy Data Tumor Growth Inhibition value (TGI)
75.60% (Day 24)
High TROP2 expression (TROP2+++)
Method Description
When the average tumor volume reached about 120 mm3, mice were randomized into five groups (n = 8) and subsequently administered by intravenous (i.v.) injection with the testing item twice a week for six times. SKB264 treatments were performed at doses of 1 mg/kg in the HCC1806.
In Vitro Model Breast squamous cell carcinoma HCC1806 cells CVCL_1258
Experiment 3 Reporting the Activity Date of This ADC [6]
Efficacy Data Tumor Growth Inhibition value (TGI)
78.40% (Day 24)
High TROP2 expression (TROP2+++)
Method Description
When the average tumor volume reached about 120 mm3, mice were randomized into five groups (n = 8) and subsequently administered by intravenous (i.v.) injection with the testing item twice a week for six times. SKB264 treatments were performed at doses of 0.3 mg/kg in the NCI-N87.
In Vitro Model Gastric tubular adenocarcinoma NCI-N87 cells CVCL_1603
Experiment 4 Reporting the Activity Date of This ADC [6]
Efficacy Data Tumor Growth Inhibition value (TGI)
98.50% (Day 24)
High TROP2 expression (TROP2+++)
Method Description
When the average tumor volume reached about 120 mm3, mice were randomized into five groups (n = 8) and subsequently administered by intravenous (i.v.) injection with the testing item twice a week for six times. SKB264 treatments were performed at doses of 3 mg/kg in the HCC1806.
In Vitro Model Breast squamous cell carcinoma HCC1806 cells CVCL_1258
Experiment 5 Reporting the Activity Date of This ADC [6]
Efficacy Data Tumor Growth Inhibition value (TGI)
100.00% (Day 24)
High TROP2 expression (TROP2+++)
Method Description
When the average tumor volume reached about 120 mm3, mice were randomized into five groups (n = 8) and subsequently administered by intravenous (i.v.) injection with the testing item twice a week for six times. SKB264 treatments were performed at doses of 10 mg/kg in the HCC1806.
In Vitro Model Breast squamous cell carcinoma HCC1806 cells CVCL_1258
Experiment 6 Reporting the Activity Date of This ADC [6]
Efficacy Data Tumor Growth Inhibition value (TGI)
100.00% (Day 24)
High TROP2 expression (TROP2+++)
Method Description
When the average tumor volume reached about 120 mm3, mice were randomized into five groups (n = 8) and subsequently administered by intravenous (i.v.) injection with the testing item twice a week for six times. SKB264 treatments were performed at doses of 1 mg/kg in the NCI-N87.
In Vitro Model Gastric tubular adenocarcinoma NCI-N87 cells CVCL_1603
Revealed Based on the Cell Line Data
Click To Hide/Show 6 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [6]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
1.28 nM
High TROP2 expression (TROP2+++)
Method Description
Tumor cells were seeded on 96-well plates at the following concentrations:Calu-3 (8,000 cells per well),After overnight incubation,the diluted testing items were added respectively. After 72 h, cell viability was evaluated using a CellTiter-Glo Luminescent Cell Viability Assay.
In Vitro Model Lung adenocarcinoma Calu-3 cells CVCL_0609
Experiment 2 Reporting the Activity Date of This ADC [6]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
2.24 nM
High TROP2 expression (TROP2+++)
Method Description
Tumor cells were seeded on 96-well plates at the following concentrations: NCI-N87 (5,000 cells per well),After overnight incubation,the diluted testing items were added respectively. After 72 h, cell viability was evaluated using a CellTiter-Glo Luminescent Cell Viability Assay.
In Vitro Model Gastric tubular adenocarcinoma NCI-N87 cells CVCL_1603
Experiment 3 Reporting the Activity Date of This ADC [6]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
3.41 nM
High TROP2 expression (TROP2+++)
Method Description
Tumor cells were seeded on 96-well plates at the following concentrations: NCI-H23 (TROP2+, 3,000 cells per well),After overnight incubation,the diluted testing items were added respectively. After 72 h, cell viability was evaluated using a CellTiter-Glo Luminescent Cell Viability Assay.
In Vitro Model Lung adenocarcinoma NCI-H23 cells CVCL_1547
Experiment 4 Reporting the Activity Date of This ADC [6]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
5.70 nM
High TROP2 expression (TROP2+++)
Method Description
Tumor cells were seeded on 96-well plates at the following concentrations: HCC1806 (3,000 cells per well),After overnight incubation,the diluted testing items were added respectively. After 72 h, cell viability was evaluated using a CellTiter-Glo Luminescent Cell Viability Assay.
In Vitro Model Breast squamous cell carcinoma HCC1806 cells CVCL_1258
Experiment 5 Reporting the Activity Date of This ADC [6]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
11.03 nM
High TROP2 expression (TROP2+++)
Method Description
Tumor cells were seeded on 96-well plates at the following concentrations: BxPC-3 (2,000 cells per well),After overnight incubation,the diluted testing items were added respectively. After 72 h, cell viability was evaluated using a CellTiter-Glo Luminescent Cell Viability Assay.
In Vitro Model Pancreatic ductal adenocarcinoma BxPC-3 cells CVCL_0186
Experiment 6 Reporting the Activity Date of This ADC [6]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
18.83 nM
Negative TROP2 expression (TROP2-)
Method Description
Tumor cells were seeded on 96-well plates at the following concentrations: NCIH23 (parental, 3,000 cells per well).After overnight incubation,the diluted testing items were added respectively. After 72 h, cell viability was evaluated using a CellTiter-Glo Luminescent Cell Viability Assay.
In Vitro Model Lung adenocarcinoma NCI-H23 cells CVCL_1547
References
Ref 1 A Randomized, Controlled, Open-label, Multi-center Phase III Clinical Trial of SKB264 for Injection Versus Investigator Selected Regimens in Patients With Unresectable Locally Advanced, Recurrent or Metastatic Triple-negative Breast Cancer Who Have Failed Second-line or Above Prior Standard of Care, NCT05347134
Ref 2 A Multicenter, Open-label, Phase 2, Basket Study to Evaluate the Efficacy and Safety of SKB264 in Combination With Pembrolizumab in Subjects With Selected Solid Tumors, NCT05642780
Ref 3 A Multicenter, Open-label, Phase 2 Study to Evaluate the Efficacy and Safety of SKB264 Monotherapy in Selected Subjects With Advanced Solid Tumors, NCT05631262
Ref 4 A Phase Clinical Study of SKB264 With/Without KL-A167 in Patients With Unresectable Locally Advanced, Recurrent or Metastatic Triple-negative Breast Cancer (TNBC) Who Have Not Received Prior Systemic Therapy, NCT05445908
Ref 5 A Phase Clinical Study of Combination Therapy of SKB264 in Patients With Advanced or Metastatic Non-small Cell Lung Cancer, NCT05351788
Ref 6 Preclinical profiles of SKB264, a novel anti-TROP2 antibody conjugated to topoisomerase inhibitor, demonstrated promising antitumor efficacy compared to IMMU-132. Front Oncol. 2022 Dec 23;12:951589.

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