CINACALCET

/static/temp/default.svg

Search structure


Synonyms	AMG 073 AMG-073 AMG073 Cinacalcet KRN-1493 KRN1493 Sensipar
Status
Molecule Category	Free-form
ATC	H05BX01
UNII	UAZ6V7728S
EPA CompTox	DTXSID8048286


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

Structure


InChI Key	VDHAWDNDOKGFTD-MRXNPFEDSA-N
Smiles	C[C@@H](NCCCc1cccc(C(F)(F)F)c1)c1cccc2ccccc12
InChI	InChI=1S/C22H22F3N/c1-16(20-13-5-10-18-9-2-3-12-21(18)20)26-14-6-8-17-7-4-11-19(15-17)22(23,24)25/h2-5,7,9-13,15-16,26H,6,8,14H2,1H3/t16-/m1/s1

Physicochemical Descriptors

Property Name	Value
Molecular Formula	C22H22F3N
Molecular Weight	357.42
AlogP	6.14
Hydrogen Bond Acceptor	1.0
Hydrogen Bond Donor	1.0
Number of Rotational Bond	6.0
Polar Surface Area	12.03
Molecular species	BASE
Aromatic Rings	3.0
Heavy Atoms	26.0

Assay Description	Organism	Bioactivity	Reference
Positive allosteric modulation of human CaSR transfected in CHO cells after 5 hrs by luciferase reporter gene assay	Homo sapiens	80.0 nM
Potentiation of human GlyR-alpha1 expressed in Xenopus laevis oocytes assessed as induction of glycine-activated currents after 1 to 4 days by two-electrode voltage clamp assay	Homo sapiens	320.0 nM
Inhibition Assay: Incubations were conducted in 96 well microtiter plates based on a method described by BD Biosciences. To the first well in each row, a NADPH regenerating system and test compound was added. In the second well and all remaining wells, NADPH regenerating system and acetonitrile (final concentration of 2%) was added. The final assay concentration of the NADPH regenerating system was 8.2 uM NADP+, 0.41 mM glucose-6-phosphate, 0.41 mM magnesium chloride hexahydrate and 0.4 U/ml glucose-6-phosphate dehydrogenase and 0.01 mg/mL control insect cell membrane protein. The test compound solution was serially diluted 1:3 through the eighth wells.The final concentration of the test compounds were in the range 100 uM to 45.7 nM in the eight rows. Wells 9 and 10 contained no test compound (only NADPH regenerating system and enzyme/substrate mix) and wells 11 and 12 were used as controls for background fluorescence (enzyme and substrate were added after the reaction was terminated). The plate was then pre-incubated at 37° C. for 10 min, and the reaction was initiated by the addition of pre-warmed enzyme/substrate mix. The assay concentration of the enzyme/substrate mix was 100 mM potassium phosphate, pH 7.4, 1.5 pmol recombinant human P450 CYP2D6 and 1.5 uM of the fluorescent substrate 3-[2-(N,N diethyl-N-methylamino)ethyl]-7-methoxy-4-methylcounnarin (AMMC). The assay was conducted in duplicate in a final volume of 200 uL per well. Reactions were terminated after 30 min by addition of a 4:1, acetonitrile:0.5 M Tris base solution. Quinidine was used as positive control, 0.5 uM as highest concentration. Fluorescence per well was measured using a fluorescence plate reader (excitation: 390 nm, emission: 460 nm).	Homo sapiens	50.0 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	18.38 %		SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate	Severe acute respiratory syndrome coronavirus 2	26.28 %
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	-0.38 %		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	-0.38 %		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	-0.38 %		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	-0.38 %

Cross References

Resources	Reference
ChEBI	48390
ChEMBL	CHEMBL1201284
DrugBank	DB01012
DrugCentral	647
FDA SRS	UAZ6V7728S
Human Metabolome Database	HMDB0015147
Guide to Pharmacology	3308
PDB	YP4
PharmGKB	PA164776671
PubChem	156419
SureChEMBL	SCHEMBL71876
ZINC	ZINC000001550499

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).