Payload Information

General Information of This Payload

Payload ID	PAY0MQMQP
Name	IMSA172
Synonyms	IMSA172 Click to Show/Hide
Target(s)	Stimulator of interferon genes protein (STING1)			Target Info
Structure
Structure	3D MOL		2D MOL
Formula	C22H29N11O12P2
Isosmiles	NCCC1C2CO[PH](=O)(=O)OC3C(COP(=O)(O)OC1C(n1cnc4c(=O)[nH]c(N)nc41)O2)OC(n1cnc2c(N)ncnc21)C3O
InChI	InChI=1S/C22H28N11O12P2/c23-2-1-8-9-3-40-47(38,39)45-15-10(43-20(13(15)34)32-6-28-11-16(24)26-5-27-17(11)32)4-41-46(36,37)44-14(8)21(42-9)33-7-29-12-18(33)30-22(25)31-19(12)35/h5-10,13-15,20-21,34H,1-4,23H2,(H,36,37)(H2,24,26,27)(H3,25,30,31,35)
InChIKey	FPGNFTNHECGXAF-UHFFFAOYSA-N
Pharmaceutical Properties	Molecule Weight	701.487	Polar area	332.28
	Complexity	47	xlogp Value	-1.5669
	Heavy Count	47	Rot Bonds	4
	Hbond acc	21	Hbond Donor	6

The activity data of This Payload

Standard Type	Value	Units	Cell line	Disease Model	Cell line ID	Reference
Half-maximal effective concentration (EC50)	35	uM	THP1-Blue ISG cells	Acute monoblastic leukemia	CVCL_X588	[1]

Each Antibody-drug Conjugate Related to This Payload

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

Hu-Alpha-EGFR-172 [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					[2]
Efficacy Data	Tumor Growth Inhibition value (TGI)	90.30% (Day 18)	High EGFR expression (EGFR+++)
Method Description	To test the effect of STING ADCs in vivo, we used a mouse tumor model in which the C57BL/6J mice were implanted subcutaneously with B16F10 melanoma cells stably expressing human EGFR (B16-EGFR). After the tumors grew to ~100 mm 3 , STING ADCs were administered to the mice through intraperitoneal injection three times (200 g each time on day 5, 8, and 11 after tumor cell inoculation). Click to Show/Hide
In Vivo Model	Melanoma CDX model
In Vitro Model	Mouse melanoma	B16-F10 cells		CVCL_0159

Revealed Based on the Cell Line Data

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

Experiment 1 Reporting the Activity Date of This ADC					[2]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	> 10.00 uM	Negative EGFR expression (EGFR-)
Method Description	Serial dilutions of IMSA172 or its conjugates with the indicated antibodies (ADCs) were incubated with THP1-ISG-Luc or this cell line stably expressing human EGFR (THP1-ISG-luc-EGFR; B and D) for 16 h, and the interferon response was measured by luciferase assay.
In Vitro Model	Acute monocytic leukemia	THP1-Lucia ISG cells		CVCL_X587

Mu-Alpha-EGFR-172 [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					[2]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	1.30 nM	High EGFR expression (EGFR+++)
Method Description	Serial dilutions of IMSA172 or its conjugates with the indicated antibodies (ADCs) were incubated with THP1-ISG-Luc or this cell line stably expressing human EGFR (THP1-ISG-luc-EGFR; B and D) for 16 h, and the interferon response was measured by luciferase assay.
In Vitro Model	Acute monocytic leukemia	THP1-Lucia ISG cells		CVCL_X587
Experiment 2 Reporting the Activity Date of This ADC					[2]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	> 10.00 uM	Negative EGFR expression (EGFR-)
Method Description	Serial dilutions of IMSA172 or its conjugates with the indicated antibodies (ADCs) were incubated with THP1-ISG-Luc or this cell line stably expressing human EGFR (THP1-ISG-luc-EGFR; B and D) for 16 h, and the interferon response was measured by luciferase assay.
In Vitro Model	Acute monocytic leukemia	THP1-Lucia ISG cells		CVCL_X587

Hu-Alpha-EGFR (ACVC)-172 [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					[2]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	1.50 nM	High EGFR expression (EGFR+++)
Method Description	Serial dilutions of IMSA172 or its conjugates with the indicated antibodies (ADCs) were incubated with THP1-ISG-Luc or this cell line stably expressing human EGFR (THP1-ISG-luc-EGFR; B and D) for 16 h, and the interferon response was measured by luciferase assay.
In Vitro Model	Acute monocytic leukemia	THP1-Lucia ISG cells		CVCL_X587
Experiment 2 Reporting the Activity Date of This ADC					[2]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	> 10.00 uM	Negative EGFR expression (EGFR-)
Method Description	Serial dilutions of IMSA172 or its conjugates with the indicated antibodies (ADCs) were incubated with THP1-ISG-Luc or this cell line stably expressing human EGFR (THP1-ISG-luc-EGFR; B and D) for 16 h, and the interferon response was measured by luciferase assay.
In Vitro Model	Acute monocytic leukemia	THP1-Lucia ISG cells		CVCL_X587

References

Ref 1	Tumor-targeted delivery of a STING agonist improvescancer immunotherapy. Proc Natl Acad Sci U S A. 2022 Dec 6;119(49):e2214278119.
Ref 2	Tumor-targeted delivery of a STING agonist improvescancer immunotherapy. Proc Natl Acad Sci U S A. 2022 Dec 6;119(49):e2214278119.