APREPITANT

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Search structure


Trade Names	APREPITANT CINVANTI EMEND
Synonyms	Aprepitant Cinvanti Emend L-754,030 MK-0869 MK-869 NSC-748825
Status
Molecule Category	UNKNOWN
ATC	A04AD12
UNII	1NF15YR6UY
EPA CompTox	DTXSID3049047


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

Structure


InChI Key	ATALOFNDEOCMKK-OITMNORJSA-N
Smiles	C[C@@H](O[C@H]1OCCN(Cc2n[nH]c(=O)[nH]2)[C@H]1c1ccc(F)cc1)c1cc(C(F)(F)F)cc(C(F)(F)F)c1
InChI	InChI=1S/C23H21F7N4O3/c1-12(14-8-15(22(25,26)27)10-16(9-14)23(28,29)30)37-20-19(13-2-4-17(24)5-3-13)34(6-7-36-20)11-18-31-21(35)33-32-18/h2-5,8-10,12,19-20H,6-7,11H2,1H3,(H2,31,32,33,35)/t12-,19+,20-/m1/s1

Physicochemical Descriptors

Property Name	Value
Molecular Formula	C23H21F7N4O3
Molecular Weight	534.43
AlogP	4.95
Hydrogen Bond Acceptor	5.0
Hydrogen Bond Donor	2.0
Number of Rotational Bond	6.0
Polar Surface Area	83.24
Molecular species	NEUTRAL
Aromatic Rings	3.0
Heavy Atoms	37.0

Bioactivity

Mechanism of Action	Action	Reference
Neurokinin 1 receptor antagonist	ANTAGONIST	DailyMed


Protein: Neurokinin 1 receptor Description: Substance-P receptor Organism : Homo sapiens P25103 ENSG00000115353

Targets	EC50(nM)	IC50(nM)	Kd(nM)	Ki(nM)	Inhibition(%)
Enzyme Cytochrome P450 Cytochrome P450 family 3 Cytochrome P450 family 3A Cytochrome P450 3A4	-	46	-	-	-
Membrane receptor Family A G protein-coupled receptor Peptide receptor (family A GPCR) Short peptide receptor (family A GPCR) Neurokinin receptor	-	0-0	8	0-3	-

Assay Description	Organism	Bioactivity	Reference
Displacement of [125I]-labeled SP from the human Tachykinin receptor 1 expressed in CHO cells	Homo sapiens	0.09 nM
In vitro inhibition of binding of [125I]-substance P to tachykinin receptor 1	None	0.09 nM
compounds were evaluated for inhibitory activity against human Tachykinin receptor 1	None	0.09 nM
Binding affinity against human Tachykinin receptor 1 expressed in CHO cells using [3H]-substance P as the radioligand	None	0.1 nM
Displacement of [125I]SP from human cloned NK1 receptor expressed in CHO cells	Homo sapiens	0.09 nM
Displacement of [125I]SP from human cloned NK1 receptor expressed in CHO cells	Homo sapiens	0.09 nM
Displacement of [125I]SP from human NK1 receptor expressed in CHO cells	Homo sapiens	0.09 nM
Inhibition of human CYP3A4	Homo sapiens	46.0 nM
Inhibition of NK1 receptor	None	0.09 nM
Displacement of [3H]osanetant from wild type human NK3 receptor expressed in HEK293 cells	Homo sapiens	454.1 nM
Displacement of radioligand [3H]SP from human NK1 F264Y6.51 mutant expressed in HEK293 cells	Homo sapiens	0.8 nM
Displacement of radioligand [3H]SP from wild type human NK1 receptor expressed in HEK293 cells	Homo sapiens	3.0 nM
Competitive inhibition of human NK1 F264Y6.51 mutant expressed in HEK293 cells assessed as decrease in SP1-induced [3H]IP accumulation after 20 mins	Homo sapiens	8.318 nM
Antagonist activity at NK1 receptor (unknown origin)	Homo sapiens	0.09 nM
Binding affinity to NK1 receptor (unknown origin)	Homo sapiens	0.07943 nM
Displacement of [125I]-substance P from gerbil NK1 receptor expressed in HEK293 cell membranes incubated for 30 mins by liquid scintillation counting method	Gerbillinae	0.09 nM
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate	Severe acute respiratory syndrome coronavirus 2	18.68 %
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging	Chlorocebus sabaeus	0.1 %		Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging	Chlorocebus sabaeus	0.1 %
Antagonist activity at NK1R (unknown origin) in presence of endogenous SP ligand preincubated for 10 mins followed by 30 min incubation with antagonist and SP by HTRF-FRET assay	Homo sapiens	1.41 nM

Related Entries

Cross References

Resources	Reference
ChEBI	499361
ChEMBL	CHEMBL1471
DrugBank	DB00673
DrugCentral	230
FDA SRS	1NF15YR6UY
Human Metabolome Database	HMDB0014811
Guide to Pharmacology	3490
KEGG	D02968
PDB	GBQ
PubChem	135413536
SureChEMBL	SCHEMBL264924
ZINC	ZINC000027428713

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).