Linker ID	LIN0FSRSR
Linker Name	AcLys-Val-Cit-PABC
Linker Type	Cathepsin-cleavable linker
Antibody-Linker Relation	Cleavable
Structure
	3D MOL			2D MOL
Formula	C26H43N7O6
Isosmiles	CC(=O)NC(CCCCN)C(=O)NC(C(=O)NC(CCCNC(N)=O)C(=O)Nc1ccc(CO)cc1)C(C)C
InChI	InChI=1S/C26H43N7O6/c1-16(2)22(33-24(37)20(30-17(3)35)7-4-5-13-27)25(38)32-21(8-6-14-29-26(28)39)23(36)31-19-11-9-18(15-34)10-12-19/h9-12,16,20-22,34H,4-8,13-15,27H2,1-3H3,(H,30,35)(H,31,36)(H,32,38)(H,33,37)(H3,28,29,39)
InChIKey	CCRUWWKFMKVBQV-UHFFFAOYSA-N
Pharmaceutical Properties	Molecule Weight		549.673	Polar area		217.77
	Complexity		39	xlogp Value		-0.1748
	Heavy Count		39	Rot Bonds		17
	Hbond acc		7	Hbond Donor		8

Experiment 1 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	4.70 nM	High CXCR4 expression (CXCR4+++)
Method Description	Cells were seeded in a culture-treated 96-well clear plate and incubated at 37°C under 5% CO2 for 24h. Serially diluted samples (50L) were added to each well and the plate was incubated at 37°C for 72h.
In Vitro Model	T acute lymphoblastic leukemia	Jurkat cells		CVCL_0065

Experiment 1 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	4.70 nM	High CXCR4 expression (CXCR4+++)
Method Description	Cells were seeded in a culture-treated 96-well clear plate and incubated at 37°C under 5% CO2 for 24h. Serially diluted samples (50L) were added to each well and the plate was incubated at 37°C for 72h.
In Vitro Model	T acute lymphoblastic leukemia	Jurkat cells		CVCL_0065

Experiment 1 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	4.70 nM	High CXCR4 expression (CXCR4+++)
Method Description	Cells were seeded in a culture-treated 96-well clear plate and incubated at 37°C under 5% CO2 for 24h. Serially diluted samples (50L) were added to each well and the plate was incubated at 37°C for 72h.
In Vitro Model	T acute lymphoblastic leukemia	Jurkat cells		CVCL_0065

Experiment 1 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	5.50 nM	High CXCR4 expression (CXCR4+++)
Method Description	Cells were seeded in a culture-treated 96-well clear plate and incubated at 37°C under 5% CO2 for 24h. Serially diluted samples (50L) were added to each well and the plate was incubated at 37°C for 72h.
In Vitro Model	T acute lymphoblastic leukemia	Jurkat cells		CVCL_0065

Experiment 1 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	17.10 nM	High CXCR4 expression (CXCR4+++)
Method Description	Cells were seeded in a culture-treated 96-well clear plate and incubated at 37°C under 5% CO2 for 24h. Serially diluted samples (50L) were added to each well and the plate was incubated at 37°C for 72h.
In Vitro Model	T acute lymphoblastic leukemia	Jurkat cells		CVCL_0065

Experiment 1 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	17.70 nM	High CXCR4 expression (CXCR4+++)
Method Description	Cells were seeded in a culture-treated 96-well clear plate and incubated at 37°C under 5% CO2 for 24h. Serially diluted samples (50L) were added to each well and the plate was incubated at 37°C for 72h.
In Vitro Model	T acute lymphoblastic leukemia	Jurkat cells		CVCL_0065

Experiment 1 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	39.70 nM	High CXCR4 expression (CXCR4+++)
Method Description	Cells were seeded in a culture-treated 96-well clear plate and incubated at 37°C under 5% CO2 for 24h. Serially diluted samples (50L) were added to each well and the plate was incubated at 37°C for 72h.
In Vitro Model	T acute lymphoblastic leukemia	Jurkat cells		CVCL_0065

Experiment 1 Reporting the Activity Date of This ADC					[2]
Efficacy Data	Objective Response Rate (ORR)	0.00%
Patients Enrolled	Advanced solid tumors resistant to standard therapy, or for which no other therapy was available, and at least one measurable lesion defined by Response Evaluation Criteria in Solid Tumors (RECIST version 1.1).
Administration Dosage	Once every 21 days as an intravenous infusion over approximately 60 min, doses starting from 0.15 mg/kg to 6.14 mg/kg.
Related Clinical Trial
NCT Number	NCT02122146	Clinical Status	Phase 1
Clinical Description	A phase 1, dose escalation study of Pf-06664178 in patients with locally advanced or metastatic solid tumors.
Primary Endpoint	In the 29 response-evaluable patients,the best overall response observed was limited to stable disease (SD) in 11 patients(37.90%) with PR or CR.
Other Endpoint	Doses explored ranged from 0.15 mg/kg to 4.80 mg/kg. Doses of 3.60 mg/kg,4.20 mg/kg and 4.80 mg/kg were considered intolerable due to DLTs. MTD and RP2D were not determined.

Ref 1	Optimal design, anti-tumour efficacy and tolerability of anti-CXCR4 antibody drug conjugates. Sci Rep. 2019 Feb 21;9(1):2443. doi: 10.1038/s41598-019-38745-x.
Ref 2	A phase 1, dose-escalation study of PF-06664178, an anti-Trop-2/Aur0101 antibody-drug conjugate in patients with advanced or metastatic solid tumors. Invest New Drugs. 2018 Oct;36(5):836-847.