PRALATREXATE

/static/temp/default.svg

Search structure


Trade Names	FOLOTYN PRALATREXATE
Synonyms	Folotyn NSC-754230 PDX Pralatrexate
Status
Molecule Category	UNKNOWN
ATC	L01BA05
UNII	A8Q8I19Q20
EPA CompTox	DTXSID3048578


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

Structure


InChI Key	OGSBUKJUDHAQEA-WMCAAGNKSA-N
Smiles	C#CCC(Cc1cnc2nc(N)nc(N)c2n1)c1ccc(C(=O)N[C@@H](CCC(=O)O)C(=O)O)cc1
InChI	InChI=1S/C23H23N7O5/c1-2-3-14(10-15-11-26-20-18(27-15)19(24)29-23(25)30-20)12-4-6-13(7-5-12)21(33)28-16(22(34)35)8-9-17(31)32/h1,4-7,11,14,16H,3,8-10H2,(H,28,33)(H,31,32)(H,34,35)(H4,24,25,26,29,30)/t14?,16-/m0/s1

Physicochemical Descriptors

Property Name	Value
Molecular Formula	C23H23N7O5
Molecular Weight	477.48
AlogP	0.98
Hydrogen Bond Acceptor	9.0
Hydrogen Bond Donor	5.0
Number of Rotational Bond	10.0
Polar Surface Area	207.3
Molecular species	ACID
Aromatic Rings	3.0
Heavy Atoms	35.0

Bioactivity

Mechanism of Action	Action	Reference
Dihydrofolate reductase inhibitor	INHIBITOR	DailyMed


Protein: Dihydrofolate reductase Description: Dihydrofolate reductase Organism : Homo sapiens P00374 ENSG00000228716

Targets	EC50(nM)	IC50(nM)	Kd(nM)	Ki(nM)	Inhibition(%)
Membrane receptor	-	168	-	-	-
Transporter Electrochemical transporter SLC superfamily of solute carriers SLC19 family of vitamin transporters	-	1	-	-	-
Transporter Electrochemical transporter SLC superfamily of solute carriers SLC46 family of folate transporters	-	57	-	-	-

Assay Description	Organism	Bioactivity	Reference
Growth inhibition of human KB cells expressing human RFC/FRalpha/PCFT after 96 hrs by CellTiter-blue assay in presence of folic acid	Homo sapiens	1.94 nM
Growth inhibition of human KB cells expressing human RFC/FRalpha/PCFT after 96 hrs by CellTiter-blue assay	Homo sapiens	0.47 nM
Growth inhibition of Chinese hamster R2 cells expressing human PCFT4 after 96 hrs by CellTiter-blue assay	Cricetulus griseus	57.0 nM
Growth inhibition of Chinese hamster RT16 cells after 96 hrs by CellTiter-blue assay	Cricetulus griseus	168.0 nM
Growth inhibition of Chinese hamster MTXRII-OuaR2-4 cells after 96 hrs by CellTiter-blue assay	Cricetulus griseus	819.0 nM
Growth inhibition of Chinese hamster PC43-10 cells after 96 hrs by CellTiter-blue assay	Cricetulus griseus	0.69 nM
Binding affinity to human RFC expressed in Chinese hamster PC43-10 cells assessed as antiproliferative activity measured as reduction in cell viability after 96 hrs by Cell-Titer Blue assay	Homo sapiens	0.69 nM
Cytotoxicity in RFC-null Chinese hamster R2 cells assessed as reduction in cell viability measured after 96 hrs by Cell-Titer Blue assay	Cricetulus griseus	819.0 nM
Binding affinity to human FR-alpha receptor expressed in Chinese hamster RT16 cells assessed as antiproliferative activity measured as reduction in cell viability after 96 hrs by Cell-Titer Blue assay	Homo sapiens	168.0 nM
Binding affinity to human PCFT expressed in Chinese hamster R2/PCFT4 cells assessed as antiproliferative activity measured as reduction in cell viability after 96 hrs by Cell-Titer Blue assay	Homo sapiens	57.0 nM
Antiproliferative activity against human KB cells expressing human RFC/FR-alpha/PCFT assessed as reduction in cell viability measured after 96 hrs by Cell-Titer Blue assay	Homo sapiens	0.47 nM
Antiproliferative activity against human KB cells expressing human RFC/FR-alpha/PCFT assessed as reduction in cell viability measured after 96 hrs in presence of folic acid by Cell-Titer Blue assay	Homo sapiens	1.94 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	36.06 %
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate	Severe acute respiratory syndrome coronavirus 2	113.52 %		SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate	Severe acute respiratory syndrome coronavirus 2	-21.09 %
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	53.62 %		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	48.83 %		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	48.83 %		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	53.62 %
Determination of IC50 values for inhibition of SARS-CoV-2 induced cytotoxicity of VERO-E6 cells after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging	Chlorocebus sabaeus	60.0 nM		Determination of IC50 values for inhibition of SARS-CoV-2 induced cytotoxicity of VERO-E6 cells after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging	Chlorocebus sabaeus	60.0 nM

Related Entries

Cross References

Resources	Reference
ChEBI	71223
ChEMBL	CHEMBL1201746
DrugBank	DB06813
DrugCentral	4117
FDA SRS	A8Q8I19Q20
Guide to Pharmacology	6840
PubChem	148121
SureChEMBL	SCHEMBL21633

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).