SIREMADLIN

/static/temp/default.svg

Search structure


Synonyms	Hdm 201 NVP-HDM 201 Siremadlin
Status
Molecule Category	UNKNOWN
UNII	0282IF4JC8


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

Structure


InChI Key	AGBSXNCBIWWLHD-FQEVSTJZSA-N
Smiles	COc1ncc(-c2nc3c(n2C(C)C)[C@H](c2ccc(Cl)cc2)N(c2cc(Cl)cn(C)c2=O)C3=O)c(OC)n1
InChI	InChI=1S/C26H24Cl2N6O4/c1-13(2)33-21-19(30-22(33)17-11-29-26(38-5)31-23(17)37-4)25(36)34(18-10-16(28)12-32(3)24(18)35)20(21)14-6-8-15(27)9-7-14/h6-13,20H,1-5H3/t20-/m0/s1

Physicochemical Descriptors

Property Name	Value
Molecular Formula	C26H24Cl2N6O4
Molecular Weight	555.42
AlogP	4.69
Hydrogen Bond Acceptor	9.0
Hydrogen Bond Donor	0.0
Number of Rotational Bond	6.0
Polar Surface Area	104.37
Molecular species	NEUTRAL
Aromatic Rings	4.0
Heavy Atoms	38.0

Assay Description	Organism	Bioactivity	Reference
Time Resolved Fluorescence Energy Transfer (TR-FRET) Assay: The inhibition of p53-MDM2 and p53-MDM4 interactions is measured by time resolved fluorescence energy transfer (TR-FRET). Fluorescence energy transfer (or Foerster resonance energy transfer) describes an energy transfer between donor and acceptor fluorescent molecules. For this assay, human MDM2 protein (amino acids 2-188) and human MDM4 protein (amino acids 2-185), tagged with a C-terminal biotin moiety, are used in combination with a Europium labeled streptavidin (Perkin Elmer, Inc., Waltham, Mass., USA) serving as the donor fluorophore. The p53 derived, Cy5 labeled peptide Cy5-TFSDLWKLL (p53 aa18-26) is the energy acceptor. Upon excitation of the donor molecule at 340 nm, binding interaction between MDM2 or MDM4 and the p53 peptide induces energy transfer and enhanced response at the acceptor emission wavelength at 665 nm.	Homo sapiens	0.23 nM
Inhibition of MDM2 (unknown origin)	Homo sapiens	0.21 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	8.29 %
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	0.26 %		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	0.26 %

Cross References

Resources	Reference
ChEMBL	CHEMBL3653256
DrugBank	DB16331
FDA SRS	0282IF4JC8
PDB	9QW
PubChem	71678098
SureChEMBL	SCHEMBL15142060

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).