PF-06821497


Active Pharmaceutical Ingredients Bioactive chemicals	Exact Similarity SubStructure	Threshold (%) >= 70


InChI Key	RXCVUHMIWHRLDF-HXUWFJFHSA-N
Smiles	COc1cc(C)[nH]c(=O)c1CN1CCc2c(Cl)cc([C@H](OC)C3COC3)c(Cl)c2C1=O
InChI	InChI=1S/C22H24Cl2N2O5/c1-11-6-17(29-2)15(21(27)25-11)8-26-5-4-13-16(23)7-14(19(24)18(13)22(26)28)20(30-3)12-9-31-10-12/h6-7,12,20H,4-5,8-10H2,1-3H3,(H,25,27)/t20-/m1/s1

Assay Description	Organism	Bioactivity
Inhibition of EZH2 in human KARPAS422 cells assessed as reduction in H3K27me3 level after 72 hrs by ELISA	Homo sapiens	4.0 nM
Inhibition of EZH2 Y641N mutant (unknown origin) using oligonucleosomes as substrate after 60 mins in presence of [3H]SAM by scintillation counting analysis	Homo sapiens	0.1 nM
Antiproliferative activity against human KARPAS422 cells after 72 hrs by resazurin assay	Homo sapiens	6.0 nM
In vivo inhibition of EZH2 in mouse xenografted with human KARPAS422 cells harboring EZH2 Y641N mutant assessed as reduction in H3K27me3 level in tumor at 100 mg/kg, sc qd measured 4 hrs post last dose on day 9 relative to control	Mus musculus	13.8 %
In vivo inhibition of EZH2 in mouse xenografted with human KARPAS422 cells harboring EZH2 Y641N mutant assessed as reduction in H3K27me3 level in tumor at 100 mg/kg, po bid measured 4 hrs post last dose on day 9 relative to control	Mus musculus	45.4 %
In vivo inhibition of EZH2 in mouse xenografted with human KARPAS422 cells harboring EZH2 Y641N mutant assessed as reduction in H3K27me3 level in tumor at 300 mg/kg, po bid measured 4 hrs post last dose on day 9 relative to control	Mus musculus	47.9 %
Binding affinity to EZH1 (unknown origin)	Homo sapiens	70.0 nM
Binding affinity to EZH2 (unknown origin)	Homo sapiens	0.1 nM

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