Payload Information

General Information of This Payload

Payload ID	PAY0QKJME
Name	PBD-based payload 37b3
Synonyms	Anticancer agent 81; Payload 37b3; Payload-37b3; GLXC-26141; HY-151207; CS-0608498; (S)-2-(2-(4-(5-((2-(4-Aminophenyl)-7-methoxy-5-oxo-5,11a-dihydro-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepin-8-yl)oxy)pentyl)piperazin-1-yl)ethyl)-1H-dibenzo[de,h]isoquinoline-1,3(2H)-dione Click to Show/Hide
Target(s)	Human Deoxyribonucleic acid (hDNA)			Target Info
Structure
Structure	3D MOL		2D MOL
Formula	C46H46N6O5
Isosmiles	COC1=C(C=C2C(=C1)C(=O)N3C=C(C[C@H]3C=N2)C4=CC=C(C=C4)N)OCCCCCN5CCN(CC5)CCN6C(=O)C7=CC=CC8=CC9=CC=CC=C9C(=C87)C6=O
PubChem CID	164946732
InChI	InChI=1S/C46H46N6O5/c1-56-40-26-38-39(48-28-35-25-33(29-52(35)45(38)54)30-12-14-34(47)15-13-30)27-41(40)57-23-6-2-5-16-49-17-19-50(20-18-49)21-22-51-44(53)37-11-7-9-32-24-31-8-3-4-10-36(31)43(42(32)37)46(51)55/h3-4,7-15,24,26-29,35H,2,5-6,16-23,25,47H2,1H3/t35-/m0/s1
InChIKey	OQPINPWCKSKRPT-DHUJRADRSA-N
IUPAC Name	15-[2-[4-[5-[[(6aS)-8-(4-aminophenyl)-2-methoxy-11-oxo-6a,7-dihydropyrrolo[2,1-c][1,4]benzodiazepin-3-yl]oxy]pentyl]piperazin-1-yl]ethyl]-15-azatetracyclo[7.7.1.02,7.013,17]heptadeca-1(17),2,4,6,8,10,12-heptaene-14,16-dione
Pharmaceutical Properties	Molecule Weight	762.9	Polar area	121
	Complexity	1510	xlogp Value	5.7
	Heavy Count	57	Rot Bonds	12
	Hbond acc	9	Hbond Donor	1

Each Antibody-drug Conjugate Related to This Payload

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

T-PBA [Investigative]

ADC Info

Discovered Using Cell Line-derived Xenograft Model

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

Experiment 1 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 93.10% (Day 30)	High HER2 expression (HER2+++)
Method Description	The efficacy of T-PBA was evaluated in two HER2-positive xenograft models at different doses and schedules. T-PBA (10 mg/kg), trastuzumab (10 mg/kg), and saline were injected by tail vein to balb/C nude mice for 0, 3, 6, and 9 days.
In Vivo Model	NCI-N87 CDX model
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603
Experiment 2 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 95.20% (Day 30)	High HER2 expression (HER2+++)
Method Description	The efficacy of T-PBA was evaluated in two HER2-positive xenograft models at different doses and schedules. T-PBA (10 mg/kg), trastuzumab (10 mg/kg), and saline were injected by tail vein to balb/C nude mice for 0, 3, 6, and 9 days.
In Vivo Model	SK-OV-3 CDX model
In Vitro Model	Ovarian serous cystadenocarcinoma	SK-OV-3 cells		CVCL_0532

Revealed Based on the Cell Line Data

Click To Hide/Show 3 Activity Data Related to This Level

Experiment 1 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	5.40 nM	High HER2 expression (HER2+++)
Method Description	Cell Counting Kit-8 (Dojindo Laboratories) was used to measure cell viability. Exponentially growing cells were seeded in 96-well plates (100 muL/well) and incubated at 37°C for 24 h.
In Vitro Model	Ovarian serous cystadenocarcinoma	SK-OV-3 cells		CVCL_0532
Experiment 2 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	56.10 nM	High HER2 expression (HER2+++)
Method Description	Cell Counting Kit-8 (Dojindo Laboratories) was used to measure cell viability. Exponentially growing cells were seeded in 96-well plates (100 muL/well) and incubated at 37°C for 24 h.
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603
Experiment 3 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	344.60 nM	High HER2 expression (HER2+++)
Method Description	Cell Counting Kit-8 (Dojindo Laboratories) was used to measure cell viability. Exponentially growing cells were seeded in 96-well plates (100 muL/well) and incubated at 37°C for 24 h.
In Vitro Model	Breast adenocarcinoma	MDA-MB-231 cells		CVCL_0062

References

Ref 1	Design, Synthesis, and Bioevaluation of a Novel Hybrid Molecular Pyrrolobenzodiazepine-Anthracenecarboxyimide as a Payload for Antibody-Drug Conjugate. J Med Chem. 2022 Sep 8;65(17):11679-11702. doi: 10.1021/acs.jmedchem.2c00471. Epub 2022 Aug 18.