Linker Information
General Information of This Linker
| Linker ID |
LIN0RZUFV
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| Linker Name |
Val-Cit linker
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| Linker Type |
Cathepsin-cleavable linker
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| Antibody-Linker Relation |
Cleavable
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| Structure |
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| Formula |
C13H23BrN4O5
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| Isosmiles |
OC([C@H](CCCNC(N)=O)NC([C@H](C(C)C)NC(CBr)=O)=O)=O
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| InChI |
InChI=1S/C13H23BrN4O5/c1-7(2)10(18-9(19)6-14)11(20)17-8(12(21)22)4-3-5-16-13(15)23/h7-8,10H,3-6H2,1-2H3,(H,17,20)(H,18,19)(H,21,22)(H3,15,16,23)/t8-,10-/m0/s1
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| InChIKey |
IVHMRMZGIYFVSF-WPRPVWTQSA-N
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| Pharmaceutical Properties |
Molecule Weight
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395.254
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Polar area
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150.62
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Complexity
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407.7542476
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xlogp Value
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-0.46
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Heavy Count
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23
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Rot Bonds
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10
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Hbond acc
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4
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Hbond Donor
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5
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Each Antibody-drug Conjugate Related to This Linker
Full Information of The Activity Data of The ADC(s) Related to This Linker
SC-004 [Phase 1 (discontinued)]
Identified from the Human Clinical Data
| Experiment 1 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | progressive disease (PD) |
21%
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| Patients Enrolled |
Eligible patients must have platinum-resistant ovarian or endometrial cancer (≤3 prior lines), ECOG 0-1, adequate organ function, with exclusion for prior PBD/IND-based therapy.
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| Related Clinical Trial | |||||
| NCT Number | NCT03138408 | Clinical Status | PHASE1 | ||
| Clinical Description |
An Open Label, Phase 1 Study of SC-004 as Monotherapy and in Combination With ABBV-181 in Subjects With Epithelial Ovarian, Including Fallopian Tube and Primary Peritoneal and Endometrial Cancers
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| Primary Endpoint |
Safety evaluation includes DLT assessment (NCI CTCAE v4.03) during the first 21-day cycle and QTcF monitoring over 9 weeks.
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| Other Endpoint |
PK parameters (Ctrough, Cmax, Tmax, T1/2, AUC) will be analyzed for 1 year; efficacy endpoints (ORR, CBR, PFS, OS, DOR, DOCB) will be tracked for 2 years.
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| Experiment 2 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | partial response (PR) |
5%
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| Patients Enrolled |
Eligible patients must have platinum-resistant ovarian or endometrial cancer (≤3 prior lines), ECOG 0-1, adequate organ function, with exclusion for prior PBD/IND-based therapy.
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| Related Clinical Trial | |||||
| NCT Number | NCT03138408 | Clinical Status | PHASE1 | ||
| Clinical Description |
An Open Label, Phase 1 Study of SC-004 as Monotherapy and in Combination With ABBV-181 in Subjects With Epithelial Ovarian, Including Fallopian Tube and Primary Peritoneal and Endometrial Cancers
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| Primary Endpoint |
Safety evaluation includes DLT assessment (NCI CTCAE v4.03) during the first 21-day cycle and QTcF monitoring over 9 weeks.
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| Other Endpoint |
PK parameters (Ctrough, Cmax, Tmax, T1/2, AUC) will be analyzed for 1 year; efficacy endpoints (ORR, CBR, PFS, OS, DOR, DOCB) will be tracked for 2 years.
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38283215 ADC 22 [Investigative]
Revealed Based on the Cell Line Data
| Experiment 1 Reporting the Activity Date of This ADC | [2] | ||||
| Efficacy Data | Half Maximal Effective Concentration (EC50) |
0.72 ug/mL
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High TNF expression (TNF +++) | ||
| Method Description |
ADC1-ADC27 with a DAR value of ~4 were screened in a GRE luciferase reporter assay in K562 cells over expressing mTNF and wild-type K562 cells to assess potency resulting from targeted delivery vs. nonspecific uptake. All the ADCs were inactive in the wild-type cells, suggesting the activity seen in mTNF over expressed cells was through targeted ADC uptake followed by intracellular release of compound C1.
Click to Show/Hide
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| In Vitro Model | Blast phase chronic myelogenous leukemia, BCR-ABL1 positive, Chronic myeloid leukemia | K562 cells (TNF) | CVCL_0004 | ||
| Experiment 2 Reporting the Activity Date of This ADC | [2] | ||||
| Efficacy Data | Half Maximal Effective Concentration (EC50) | > 50 ug/mL | Negative TNF expression (TNF-) | ||
| Method Description |
ADC1-ADC27 with a DAR value of ~4 were screened in a GRE luciferase reporter assay in K562 cells over expressing mTNF and wild-type K562 cells to assess potency resulting from targeted delivery vs. nonspecific uptake. All the ADCs were inactive in the wild-type cells, suggesting the activity seen in mTNF over expressed cells was through targeted ADC uptake followed by intracellular release of compound C1.
Click to Show/Hide
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| In Vitro Model | Blast phase chronic myelogenous leukemia, BCR-ABL1 positive, Chronic myeloid leukemia | K562 cells (wt) | CVCL_0004 | ||
References