Payload Information

General Information of This Payload

Payload ID	PAY0AWJRS
Name	Phosphate prodrugs 40 (DC4)
Synonyms	Phosphate prodrugs 40 (DC4) Click to Show/Hide
Target(s)	Human Deoxyribonucleic acid (hDNA)			Target Info
Structure
Structure	3D MOL		2D MOL
Formula	C34H29ClN5O7PS
Isosmiles	O=C(CCS)Nc1ccc2[nH]c(C(=O)Nc3ccc4[nH]c(C(=O)N5CC(CCl)c6c5cc(OP(=O)(O)O)c5ccccc65)cc4c3)cc2c1
InChI	InChI=1S/C34H29ClN5O7PS/c35-16-20-17-40(29-15-30(47-48(44,45)46)23-3-1-2-4-24(23)32(20)29)34(43)28-14-19-12-22(6-8-26(19)39-28)37-33(42)27-13-18-11-21(5-7-25(18)38-27)36-31(41)9-10-49/h1-8,11-15,20,38-39,49H,9-10,16-17H2,(H,36,41)(H,37,42)(H2,44,45,46)
InChIKey	PWGCKOQNKYABMN-UHFFFAOYSA-N
Pharmaceutical Properties	Molecule Weight	718.128	Polar area	176.85
	Complexity	49	xlogp Value	6.7674
	Heavy Count	49	Rot Bonds	9
	Hbond acc	6	Hbond Donor	7

Each Antibody-drug Conjugate Related to This Payload

Full Information of The Activity Data of The ADC(s) Related to This Payload

B4-SPP-DC4 [Investigative]

ADC Info

Discovered Using Cell Line-derived Xenograft Model

Click To Hide/Show 1 Activity Data Related to This Level

Experiment 1 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 84.00% (Day 9)	Positive CD19 expression (CD19+++/++)
Method Description	Animals with established subcutaneous xenograft Ramos tumors were treated with either huB4-SPP-DC4 (DC4 dose of 75 ug/kg, qdx5), or huB4-SPP-DC44 (DC44 dose of 75 ug/kg, qdx5), unconjugated DC4 (75 ug/kg, qdx5), unconjugated DC44 (75 ug/kg, qdx5), or with phosphate-buffered saline vehicle (control), administered intravenously, and the tumor growth was monitored. Click to Show/Hide
In Vivo Model	Ramos CDX model
In Vitro Model	Burkitt lymphoma	Ramos cells		CVCL_0597

Revealed Based on the Cell Line Data

Click To Hide/Show 4 Activity Data Related to This Level

Experiment 1 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	11.00 pM	Positive CD19 expression (CD19+++/++)
Method Description	Cytotoxicity of B4-SPP-DCx Conjugates (without acid phosphatase treatment) against Ramos (Ag+) and HL60/s (Ag-) Cells.
In Vitro Model	Burkitt lymphoma	Ramos cells		CVCL_0597
Experiment 2 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.74 nM	Positive CD19 expression (CD19+++/++)
Method Description	Cytotoxicity of B4-SPP-DCx Conjugates (with acid phosphatase treatment) against Ramos (Ag+) and HL60/s (Ag-) Cells.
In Vitro Model	Burkitt lymphoma	Ramos cells		CVCL_0597
Experiment 3 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	> 1.50 nM	Negative CD19 expression(CD19-)
Method Description	Cytotoxicity of B4-SPP-DCx Conjugates (with acid phosphatase treatment) against Ramos (Ag+) and HL60/s (Ag-) Cells.
In Vitro Model	Adult acute myeloid leukemia	HL-60 cells		CVCL_0002
Experiment 4 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	> 3.00 nM	Negative CD19 expression(CD19-)
Method Description	Cytotoxicity of B4-SPP-DCx Conjugates (without acid phosphatase treatment) against Ramos (Ag+) and HL60/s (Ag-) Cells.
In Vitro Model	Adult acute myeloid leukemia	HL-60 cells		CVCL_0002

B4-SMCC-DC4 [Investigative]

ADC Info

Revealed Based on the Cell Line Data

Click To Hide/Show 2 Activity Data Related to This Level

Experiment 1 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	1.20 nM	Positive CD19 expression (CD19+++/++)
Method Description	Cytotoxicity of B4-SPP-DCx Conjugates (with acid phosphatase treatment) against Ramos (Ag+) and HL60/s (Ag-) Cells.
In Vitro Model	Burkitt lymphoma	Ramos cells		CVCL_0597
Experiment 2 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	2.60 nM	Negative CD19 expression(CD19-)
Method Description	Cytotoxicity of B4-SPP-DCx Conjugates (with acid phosphatase treatment) against Ramos (Ag+) and HL60/s (Ag-) Cells.
In Vitro Model	Adult acute myeloid leukemia	HL-60 cells		CVCL_0002

References

Ref 1	Synthesis and biological evaluation of antibody conjugates of phosphate prodrugs of cytotoxic DNA alkylators for the targeted treatment of cancer. J Med Chem. 2012 Jan 26;55(2):766-82. doi: 10.1021/jm201284m.