Payload ID	PAY0WIKAB
Name	Pyrrole based kinesin spindle protein inhibitor
Synonyms	Pyrrole based KSPi    Click to Show/Hide
Target(s)	Kinesin-like protein KIF11 (KIF11)					Target Info
Formula	C27H33F2N3O2
Isosmiles	CC(C)(C)C(c1cc(-c2cc(F)ccc2F)cn1Cc1ccccc1)N(CCCN)C(=O)CO
InChI	InChI=1S/C27H33F2N3O2/c1-27(2,3)26(32(13-7-12-30)25(34)18-33)24-14-20(22-15-21(28)10-11-23(22)29)17-31(24)16-19-8-5-4-6-9-19/h4-6,8-11,14-15,17,26,33H,7,12-13,16,18,30H2,1-3H3
Pharmaceutical Properties	Molecule Weight		469.576	Polar area		71.49
	Complexity		34	xlogp Value		4.7385
	Heavy Count		34	Rot Bonds		9
	Hbond acc		4	Hbond Donor		2

Experiment 1 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 96.95% (Day 13)	High TWEAKR expression (TWEAKR +++)
Method Description	Efficacy of TWEAKR-ADCs 1.4 with aglycosylated TWEAKR mAb BAY-356 in the BXF1218 UCC PDX model in NMRI nude micewith 10 mg/kg.
In Vivo Model	Urothelial cell cancer PDX model (PDX: BXF1218)

Experiment 1 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 89.98% (Day 13)	High TWEAKR expression (TWEAKR +++)
Method Description	Efficacy of TWEAKR-ADCs 2.2with aglycosylated TWEAKR mAb BAY-356 in the NCI-H292 NSCLC xenograft model in NMRI nude micewith 10 mg/kg.
In Vivo Model	NCI-H292 CDX model
In Vitro Model	Lung mucoepidermoid carcinoma	NCI-H292 cells		CVCL_0455

Experiment 1 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.94 nM	High TWEAKR expression (TWEAKR +++)
Method Description	In vitro potency of SMOL KSPi compound A and of TWEAKR-KSPiADCs 1.1., 1.2, 1.3, 1.4, 2.1, and 2.2 in TWEAKR-expressing cell lines versus selected respective isotype control ADCs 1.4 and 2.2 with same linker payload chemistry.
In Vitro Model	Lung mucoepidermoid carcinoma	NCI-H292 cells		CVCL_0455
Experiment 2 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	58.00 nM	High TWEAKR expression (TWEAKR +++)
Method Description	In vitro potency of SMOL KSPi compound A and of TWEAKR-KSPiADCs 1.1., 1.2, 1.3, 1.4, 2.1, and 2.2 in TWEAKR-expressing cell lines versus selected respective isotype control ADCs 1.4 and 2.2 with same linker payload chemistry.
In Vitro Model	Colon adenocarcinoma	LoVo cells		CVCL_0399
Experiment 3 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	600 nM	High TWEAKR expression (TWEAKR +++)
Method Description	In vitro potency of SMOL KSPi compound A and of TWEAKR-KSPiADCs 1.1., 1.2, 1.3, 1.4, 2.1, and 2.2 in TWEAKR-expressing cell lines versus selected respective isotype control ADCs 1.4 and 2.2 with same linker payload chemistry.
In Vitro Model	Pancreatic ductal adenocarcinoma	BxPC-3 cells		CVCL_0186

Experiment 1 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 96.95% (Day 13)	High TWEAKR expression (TWEAKR +++)
Method Description	Efficacy of TWEAKR-ADCs 1.4 with aglycosylated TWEAKR mAb BAY-356 in the BXF1218 UCC PDX model in NMRI nude micewith 5 mg/kg.
In Vivo Model	Urothelial cell cancer PDX model (PDX: BXF1218)

Experiment 1 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 61.71% (Day 13)	High TWEAKR expression (TWEAKR +++)
Method Description	Efficacy of TWEAKR-ADCs 1.4 with aglycosylated TWEAKR mAb BAY-356 in the NCI-H292 NSCLC xenograft model in NMRI nude micewith 5 mg/kg.
In Vivo Model	NCI-H292 CDX model
In Vitro Model	Lung mucoepidermoid carcinoma	NCI-H292 cells		CVCL_0455
Experiment 2 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 86.40% (Day 13)	High TWEAKR expression (TWEAKR +++)
Method Description	Efficacy of TWEAKR-ADCs 1.4 with aglycosylated TWEAKR mAb BAY-356 in the NCI-H292 NSCLC xenograft model in NMRI nude micewith 10 mg/kg.
In Vivo Model	NCI-H292 CDX model
In Vitro Model	Lung mucoepidermoid carcinoma	NCI-H292 cells		CVCL_0455

Experiment 1 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.30 nM	High TWEAKR expression (TWEAKR +++)
Method Description	In vitro potency of SMOL KSPi compound A and of TWEAKR-KSPiADCs 1.1., 1.2, 1.3, 1.4, 2.1, and 2.2 in TWEAKR-expressing cell lines versus selected respective isotype control ADCs 1.4 and 2.2 with same linker payload chemistry.
In Vitro Model	Lung mucoepidermoid carcinoma	NCI-H292 cells		CVCL_0455
Experiment 2 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.37 nM	High TWEAKR expression (TWEAKR +++)
Method Description	In vitro potency of SMOL KSPi compound A and of TWEAKR-KSPiADCs 1.1., 1.2, 1.3, 1.4, 2.1, and 2.2 in TWEAKR-expressing cell lines versus selected respective isotype control ADCs 1.4 and 2.2 with same linker payload chemistry.
In Vitro Model	Colon adenocarcinoma	LoVo cells		CVCL_0399
Experiment 3 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	1.10 nM	High TWEAKR expression (TWEAKR +++)
Method Description	In vitro potency of SMOL KSPi compound A and of TWEAKR-KSPiADCs 1.1., 1.2, 1.3, 1.4, 2.1, and 2.2 in TWEAKR-expressing cell lines versus selected respective isotype control ADCs 1.4 and 2.2 with same linker payload chemistry.
In Vitro Model	Pancreatic ductal adenocarcinoma	BxPC-3 cells		CVCL_0186

Experiment 1 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.02 nM	Positive HER2 expression (HER2 +++/++)
Method Description	Drug-to-antibody ratios (DARs) and potency of the ADCs in the HER-2 positive breast cancer cell line KPL-4.
In Vitro Model	Breast inflammatory carcinoma	KPL-4 cells		CVCL_5310

Experiment 1 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.06 nM	High TWEAKR expression (TWEAKR +++)
Method Description	In vitro potency of SMOL KSPi compound A and of TWEAKR-KSPiADCs 1.1., 1.2, 1.3, 1.4, 2.1, and 2.2 in TWEAKR-expressing cell lines versus selected respective isotype control ADCs 1.4 and 2.2 with same linker payload chemistry.
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)	0.16 nM	High TWEAKR expression (TWEAKR +++)
Method Description	In vitro potency of SMOL KSPi compound A and of TWEAKR-KSPiADCs 1.1., 1.2, 1.3, 1.4, 2.1, and 2.2 in TWEAKR-expressing cell lines versus selected respective isotype control ADCs 1.4 and 2.2 with same linker payload chemistry.
In Vitro Model	Pancreatic ductal adenocarcinoma	BxPC-3 cells		CVCL_0186
Experiment 3 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.31 nM	High TWEAKR expression (TWEAKR +++)
Method Description	In vitro potency of SMOL KSPi compound A and of TWEAKR-KSPiADCs 1.1., 1.2, 1.3, 1.4, 2.1, and 2.2 in TWEAKR-expressing cell lines versus selected respective isotype control ADCs 1.4 and 2.2 with same linker payload chemistry.
In Vitro Model	Lung mucoepidermoid carcinoma	NCI-H292 cells		CVCL_0455

Experiment 1 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.07 nM	Positive HER2 expression (HER2 +++/++)
Method Description	Drug-to-antibody ratios (DARs) and potency of the ADCs in the HER-2 positive breast cancer cell line KPL-4.
In Vitro Model	Breast inflammatory carcinoma	KPL-4 cells		CVCL_5310

Experiment 1 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.07 nM	Positive HER2 expression (HER2 +++/++)
Method Description	Drug-to-antibody ratios (DARs) and potency of the ADCs in the HER-2 positive breast cancer cell line KPL-4.
In Vitro Model	Breast inflammatory carcinoma	KPL-4 cells		CVCL_5310

Experiment 1 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.09 nM	High TWEAKR expression (TWEAKR +++)
Method Description	In vitro potency of SMOL KSPi compound A and of TWEAKR-KSPiADCs 1.1., 1.2, 1.3, 1.4, 2.1, and 2.2 in TWEAKR-expressing cell lines versus selected respective isotype control ADCs 1.4 and 2.2 with same linker payload chemistry.
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)	0.74 nM	High TWEAKR expression (TWEAKR +++)
Method Description	In vitro potency of SMOL KSPi compound A and of TWEAKR-KSPiADCs 1.1., 1.2, 1.3, 1.4, 2.1, and 2.2 in TWEAKR-expressing cell lines versus selected respective isotype control ADCs 1.4 and 2.2 with same linker payload chemistry.
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)	0.87 nM	High TWEAKR expression (TWEAKR +++)
Method Description	In vitro potency of SMOL KSPi compound A and of TWEAKR-KSPiADCs 1.1., 1.2, 1.3, 1.4, 2.1, and 2.2 in TWEAKR-expressing cell lines versus selected respective isotype control ADCs 1.4 and 2.2 with same linker payload chemistry.
In Vitro Model	Pancreatic ductal adenocarcinoma	BxPC-3 cells		CVCL_0186

Experiment 1 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.20 nM	Positive HER2 expression (HER2 +++/++)
Method Description	Drug-to-antibody ratios (DARs) and potency of the ADCs in the HER-2 positive breast cancer cell line KPL-4.
In Vitro Model	Breast inflammatory carcinoma	KPL-4 cells		CVCL_5310

Experiment 1 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.41 nM	High TWEAKR expression (TWEAKR +++)
Method Description	In vitro potency of SMOL KSPi compound A and of TWEAKR-KSPiADCs 1.1., 1.2, 1.3, 1.4, 2.1, and 2.2 in TWEAKR-expressing cell lines versus selected respective isotype control ADCs 1.4 and 2.2 with same linker payload chemistry.
In Vitro Model	Lung mucoepidermoid carcinoma	NCI-H292 cells		CVCL_0455
Experiment 2 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.97 nM	High TWEAKR expression (TWEAKR +++)
Method Description	In vitro potency of SMOL KSPi compound A and of TWEAKR-KSPiADCs 1.1., 1.2, 1.3, 1.4, 2.1, and 2.2 in TWEAKR-expressing cell lines versus selected respective isotype control ADCs 1.4 and 2.2 with same linker payload chemistry.
In Vitro Model	Pancreatic ductal adenocarcinoma	BxPC-3 cells		CVCL_0186
Experiment 3 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	600 nM	High TWEAKR expression (TWEAKR +++)
Method Description	In vitro potency of SMOL KSPi compound A and of TWEAKR-KSPiADCs 1.1., 1.2, 1.3, 1.4, 2.1, and 2.2 in TWEAKR-expressing cell lines versus selected respective isotype control ADCs 1.4 and 2.2 with same linker payload chemistry.
In Vitro Model	Colon adenocarcinoma	LoVo cells		CVCL_0399

Experiment 1 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.70 nM	Positive HER2 expression (HER2 +++/++)
Method Description	Drug-to-antibody ratios (DARs) and potency of the ADCs in the HER-2 positive breast cancer cell line KPL-4.
In Vitro Model	Breast inflammatory carcinoma	KPL-4 cells		CVCL_5310

Experiment 1 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.80 nM	Positive HER2 expression (HER2 +++/++)
Method Description	Drug-to-antibody ratios (DARs) and potency of the ADCs in the HER-2 positive breast cancer cell line KPL-4.
In Vitro Model	Breast inflammatory carcinoma	KPL-4 cells		CVCL_5310

Experiment 1 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.87 nM	High TWEAKR expression (TWEAKR +++)
Method Description	In vitro potency of SMOL KSPi compound A and of TWEAKR-KSPiADCs 1.1., 1.2, 1.3, 1.4, 2.1, and 2.2 in TWEAKR-expressing cell lines versus selected respective isotype control ADCs 1.4 and 2.2 with same linker payload chemistry.
In Vitro Model	Pancreatic ductal adenocarcinoma	BxPC-3 cells		CVCL_0186
Experiment 2 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	44.00 nM	High TWEAKR expression (TWEAKR +++)
Method Description	In vitro potency of SMOL KSPi compound A and of TWEAKR-KSPiADCs 1.1., 1.2, 1.3, 1.4, 2.1, and 2.2 in TWEAKR-expressing cell lines versus selected respective isotype control ADCs 1.4 and 2.2 with same linker payload chemistry.
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)	600 nM	High TWEAKR expression (TWEAKR +++)
Method Description	In vitro potency of SMOL KSPi compound A and of TWEAKR-KSPiADCs 1.1., 1.2, 1.3, 1.4, 2.1, and 2.2 in TWEAKR-expressing cell lines versus selected respective isotype control ADCs 1.4 and 2.2 with same linker payload chemistry.
In Vitro Model	Colon adenocarcinoma	LoVo cells		CVCL_0399

Ref 1	Antibody-Drug Conjugates with Pyrrole-Based KSP Inhibitors as the Payload Class. Angew Chem Int Ed Engl. 2018 Nov 12;57(46):15243-15247. doi: 10.1002/anie.201807619. Epub 2018 Oct 15.