Payload Information

General Information of This Payload

Payload ID	PAY0PJTCU
Name	Kinesin spindle protein (KSP) inhibitor 3g
Synonyms	KSP inhibitor 3g Click to Show/Hide
Target(s)	Kinesin-like protein KIF11 (KIF11)			Target Info
Formula	C46H57F2N9O8
Isosmiles	C[C@H](NC(=O)Cc1ccncc1)C(=O)N(C)[C@@H](C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCN(C(=O)CO)[C@@H](c1cc(-c2cc(F)ccc2F)cn1Cc1ccccc1)C(C)(C)C)C(N)=O
InChI	InChI=1S/C46H57F2N9O8/c1-27(52-39(60)20-29-14-17-51-18-15-29)45(65)55(6)28(2)43(63)54-36(23-38(49)59)44(64)53-35(42(50)62)16-19-57(40(61)26-58)41(46(3,4)5)37-21-31(33-22-32(47)12-13-34(33)48)25-56(37)24-30-10-8-7-9-11-30/h7-15,17-18,21-22,25,27-28,35-36,41,58H,16,19-20,23-24,26H2,1-6H3,(H2,49,59)(H2,50,62)(H,52,60)(H,53,64)(H,54,63)/t27-,28-,35-,36-,41-/m0/s1
Pharmaceutical Properties	Molecule Weight	902.013	Polar area	252.15
	Complexity	65	xlogp Value	2.0994
	Heavy Count	65	Rot Bonds	21
	Hbond acc	10	Hbond Donor	6

Each Antibody-drug Conjugate Related to This Payload

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

Anti-B7H3 APDC 3g [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)	≈ 94.08% (Day 30)	Positive B7H3 expression (B7H3 +++/++)
Method Description	Both APDCs (10 mg/kg) have been administered to B7H3-positive U251-glioma-tumor-bearing mice; 24hours after treatment, tumors and organs were collected.
In Vivo Model	U251 CDX model
In Vitro Model	Astrocytoma	U-251MG cells		CVCL_0021

TWEAKR ADC 3g [Investigative]

ADC Info

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)	0.30 nM	Positive TNFRSF12A expression (TNFRSF12A +++/++)
Method Description	Cytotoxicity of ADCs, SMOL KSP inhibitors, and payload metabolite were determined in TWEAKR-positive cancer cell lines 72 h after treatment with the Promega CellTiter Glo (CTG) cell viability assay according to manufacturers instructions.
In Vitro Model	Colon adenocarcinoma	LoVo cells		CVCL_0399
Experiment 2 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	2.20 nM	Positive TNFRSF12A expression (TNFRSF12A +++/++)
Method Description	Cytotoxicity of ADCs, SMOL KSP inhibitors, and payload metabolite were determined in TWEAKR-positive cancer cell lines 72 h after treatment with the Promega CellTiter Glo (CTG) cell viability assay according to manufacturers instructions.
In Vitro Model	Lung mucoepidermoid carcinoma	NCI-H292 cells		CVCL_0455
Experiment 3 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	2.30 nM	Positive TNFRSF12A expression (TNFRSF12A +++/++)
Method Description	Cytotoxicity of ADCs, SMOL KSP inhibitors, and payload metabolite were determined in TWEAKR-positive cancer cell lines 72 h after treatment with the Promega CellTiter Glo (CTG) cell viability assay according to manufacturers instructions.
In Vitro Model	Pancreatic ductal adenocarcinoma	BxPC-3 cells		CVCL_0186

References

Ref 1	Antibody-Prodrug Conjugates with KSP Inhibitors and Legumain-Mediated Metabolite Formation. Chemistry. 2019 Jun 21;25(35):8208-8213. doi: 10.1002/chem.201900441. Epub 2019 Apr 15.