MILVEXIAN


Synonyms	BMS 986177 BMS-986177 Bms-986177 JNJ-70033093 Jnj-70033093 Milvexian
Status
Molecule Category	UNKNOWN
UNII	0W79NDQ608


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

Structure


InChI Key	FSWFYCYPTDLKON-CMJOXMDJSA-N
Smiles	C[C@@H]1CCC[C@H](n2cnc(-c3cc(Cl)ccc3-n3cc(Cl)nn3)cc2=O)c2cc(ccn2)-c2c(cnn2C(F)F)NC1=O
InChI	InChI=1S/C28H23Cl2F2N9O2/c1-15-3-2-4-23(20-9-16(7-8-33-20)26-21(36-27(15)43)12-35-41(26)28(31)32)39-14-34-19(11-25(39)42)18-10-17(29)5-6-22(18)40-13-24(30)37-38-40/h5-15,23,28H,2-4H2,1H3,(H,36,43)/t15-,23+/m1/s1

Physicochemical Descriptors

Property Name	Value
Molecular Formula	C28H23Cl2F2N9O2
Molecular Weight	626.46
AlogP	5.8
Hydrogen Bond Acceptor	10.0
Hydrogen Bond Donor	1.0
Number of Rotational Bond	4.0
Polar Surface Area	125.41
Molecular species	NEUTRAL
Aromatic Rings	5.0
Heavy Atoms	43.0

Assay Description	Organism	Bioactivity
In Vitro Assay: Factor XIa determinations were made in 50 mM HEPES buffer at pH 7.4 containing 145 mM NaCl, 5 mM KCl, and 0.1% PEG 8000 (polyethylene glycol; JT Baker or Fisher Scientific). Determinations were made using purified human Factor XIa at a final concentration of 25-200 pM (Haematologic Technologies) and the synthetic substrate S-2366 (pyroGlu-Pro-Arg-pNA; CHROMOGENIX® or AnaSpec) at a concentration of 0.0002-0.001 M.	Homo sapiens	0.1 nM
In Vitro Assay: Plasma kallikrein determinations were made in 0.1 M sodium phosphate buffer at a pH of 7.5 containing 0.1-0.2 M sodium chloride and 0.5% PEG 8000. Determinations were made using purified human plasma kallikrein (Enzyme Research Laboratories) at a final assay concentration of 200 pM and the synthetic substrate S-2302 (H-(D)-Pro-Phe-Arg-pNA; CHROMOGENIX®) at a concentration of 0.00008-0.0004 M.	Homo sapiens	28.0 nM
Binding affinity to human chymotrypsin assessed as inhibition constant using 3-Carbomethoxypropionyl-L-arginyl-Lprolyl-L-tyrosine p-Nitroaniline as substrate measured upto 120 mins by spectrophotometric analysis	Homo sapiens	35.0 nM
Binding affinity to human coagulation factor 11a using L-Pyroglutamyl-L-prolyl-L-arginine p-Nitroaniline as substrate assessed as inhibition constant measured upto 120 mins by spectrophotometric analysis	Homo sapiens	0.11 nM
Binding affinity to human plasma kallikrein assessed as inhibition constant using H-D-Prolyl-L-phenylalanyl-L-arginine p-Nitroaniline as substrate measured upto 120 mins by spectrophotometric analysis	Homo sapiens	44.0 nM
Binding affinity to human trypsin assessed as inhibition constant using N-Benzoyl-L-isoleucyl-L-glutamyl-glycyl-Larginine p-Nitroaniline and its gamma glutamyl methyl ester as substrate measured upto 120 mins by spectrophotometric analysis	Homo sapiens	720.0 nM

Cross References

Resources	Reference
ChEMBL	CHEMBL4112929
DrugBank	DB16233
FDA SRS	0W79NDQ608
PubChem	118277544
SureChEMBL	SCHEMBL16982989

CONTENTS


PREMIER has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 875508. The JU receives support from the EU’s Horizon 2020 research and innovation programme and the European Federation of Pharmaceutical Industries and Associations (EFPIA). The views reflect only the authors’ perspective and the JU is not responsible for any use that may be made of the information this manuscript contains. Elements of the website have been developed under projects PREMIER and the Biocenter Finland Drug Discovery and Chemical Biology network. CSC-IT is thanked for providing computational resources. Content of the website is provided without guarantee for correctness. Data has been collected and integrated from multiple public sources, for the largest: FDA, HUGO Gene Nomenclature Committee, ChEMBL, IUPHAR/BPS guide to pharmacology, Reactome, UniProt, and Ensembl. Credit is given to Ensembl for collecting species images (provided under public domain licences such as Wikimedia and NHGRI).

PREMIER has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 875508. The JU receives support from the EU’s Horizon 2020 research and innovation programme and the European Federation of Pharmaceutical Industries and Associations (EFPIA). The views reflect only the authors’ perspective and the JU is not responsible for any use that may be made of the information this manuscript contains.

Elements of the website have been developed under projects PREMIER and the Biocenter Finland Drug Discovery and Chemical Biology network. CSC-IT is thanked for providing computational resources. Content of the website is provided without guarantee for correctness. Data has been collected and integrated from multiple public sources, for the largest: FDA, HUGO Gene Nomenclature Committee, ChEMBL, IUPHAR/BPS guide to pharmacology, Reactome, UniProt, and Ensembl. Credit is given to Ensembl for collecting species images (provided under public domain licences such as Wikimedia and NHGRI).