TAFAMIDIS

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Search structure


Trade Names	VYNDAMAX
Synonyms	FX-1005 FX-1006 FX1006 Tafamidis Vyndamax Vyndaqel
Status
Molecule Category	UNKNOWN
ATC	N07XX08
UNII	8FG9H9D31J
EPA CompTox	DTXSID00208185


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

Structure


InChI Key	TXEIIPDJKFWEEC-UHFFFAOYSA-N
Smiles	O=C(O)c1ccc2nc(-c3cc(Cl)cc(Cl)c3)oc2c1
InChI	InChI=1S/C14H7Cl2NO3/c15-9-3-8(4-10(16)6-9)13-17-11-2-1-7(14(18)19)5-12(11)20-13/h1-6H,(H,18,19)

Physicochemical Descriptors

Property Name	Value
Molecular Formula	C14H7Cl2NO3
Molecular Weight	308.12
AlogP	4.5
Hydrogen Bond Acceptor	3.0
Hydrogen Bond Donor	1.0
Number of Rotational Bond	2.0
Polar Surface Area	63.33
Molecular species	ACID
Aromatic Rings	3.0
Heavy Atoms	20.0

Bioactivity

Mechanism of Action	Action	Reference
Transthyretin stabiliser	STABILISER	PubMed


Protein: Transthyretin Description: Transthyretin Organism : Homo sapiens P02766 ENSG00000118271

Targets	EC50(nM)	IC50(nM)	Kd(nM)	Ki(nM)	Inhibition(%)
Secreted protein	-	1550-3100	3-2800	-	99

Assay Description	Organism	Bioactivity	Reference
Binding affinity to recombinant human wild type TTR expressed in Escherichia coli BL21 (DE3) assessed as dissociation constants for first binding site of TTR by isothermal titration calorimetric method	Homo sapiens	9.3 nM
Binding affinity to recombinant human wild type TTR expressed in Escherichia coli BL21 (DE3) assessed as dissociation constants for second binding site of TTR by isothermal titration calorimetric method	Homo sapiens	274.0 nM
Competitive binding affinity to human wild type TTR expressed in Escherichia coli BL-21 assessed as equilibrium dissociation constant of second site in presence of ANS by spectrofluorometer	Homo sapiens	370.0 nM
Binding affinity to wild type TTR (unknown origin) assessed as equilibrium dissociation constant of second site by isothermal titration calorimetry	Homo sapiens	278.0 nM
Inhibition of acid-induced wild type transthyretin (unknown origin) aggregation expressed in Escherichia coli pre-incubated for 30 mins before acid addition and further incubated for 72 hrs at 37 degC under dark conditions by UV-Vis spectrophotometry	Homo sapiens	99.0 %
Displacement of [125I]-triiodothyronine from thyroid hormone receptor in rat liver membrane homogenates incubated for 18 hrs by scintillation counting method	Rattus norvegicus	0.0 %
Binding affinity to transthyretin (unknown origin) by ITC method	Homo sapiens	4.4 nM
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of Caco-2 cells at 10 uM after 48 hours by high content imaging	Homo sapiens	3.87 %
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate	Severe acute respiratory syndrome coronavirus 2	16.93 %		SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate	Severe acute respiratory syndrome coronavirus 2	17.17 %
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	-0.27 %		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	-0.08 %		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	-0.27 %		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	-0.08 %
Binding affinity to wild type TTR (unknown origin) assessed as Kd1 by isothermal titration calorimetry	Homo sapiens	3.0 nM
Binding affinity to wild type TTR (unknown origin) assessed as Kd2 by isothermal titration calorimetry	Homo sapiens	278.0 nM
Binding affinity to TTR V30M mutant (unknown origin) by isothermal titration calorimetry	Homo sapiens	200.0 nM
Disruption of retional-induced bacterially expressed MBP-tagged RBP4-TTR (unknown origin) protein-protein interaction measured by d2 dye based HTFR assay	Homo sapiens	981.0 nM
Binding affinity to human plasma TTR tetramer assessed as displacement of diclofenac-coupled FITC by fluorescence polarization assay	Homo sapiens	410.0 nM

Cross References

Resources	Reference
ChEBI	78538
ChEMBL	CHEMBL2103837
DrugBank	DB11644
DrugCentral	4192
FDA SRS	8FG9H9D31J
Guide to Pharmacology	8378
PDB	3MI
PubChem	11001318
SureChEMBL	SCHEMBL442508
ZINC	ZINC000043206271

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).