Compound Detail

CHEMBL225072

PEMETREXED

💊 Approved Drug

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💊 Approved Drug

Nc1nc2[nH]cc(CCc3ccc(C(=O)N[C@@H](CCC(=O)O)C(=O)O)cc3)c2c(=O)[nH]1

ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID	CHEMBL225072
Name	PEMETREXED
Phase	Approved
Structure Type	MOL
InChI Key	WBXPDJSOTKVWSJ-ZDUSSCGKSA-N
Therapeutic	✓ Yes

Known Names

Alimta LY-231514 LY231514 NSC-698037 Pemetrexed Pemfexy

Targets

255

Activities

Assay Types

PK Parameters

Publications

Known Names

Indications

Mechanisms

Molecular Properties

427.4

MW (Da)

0.67

ALogP

HBA

HBD

191.3

PSA (Å²)

0.29

QED

Ro5 Violations

Rot. Bonds

Drug Information

Molecule Type	Small molecule
First Approval	2004
Availability	Prescription
Chirality	Single Enantiomer

Routes of Administration

Parenteral

Flags

Natural Product

USAN Stem	-trexed
USAN Year	1997

Extended Properties

Molecular Formula	C20H21N5O6
MW	427.42
Aromatic Rings	3
Heavy Atoms	31
NP-Likeness	0.07

Mechanism of Action

Mechanism	Action Type	Target	Direct	Efficacy
Dihydrofolate reductase inhibitor	INHIBITOR	Dihydrofolate reductase	✓	✓
Thymidylate synthase inhibitor	INHIBITOR	Thymidylate synthase	✓	✓
GAR transformylase inhibitor	INHIBITOR	Trifunctional purine biosynthetic protein adenosine-3	✓	✓

Indications

Mesothelioma Mesothelioma Mesothelioma Neoplasms Neoplasms Adenocarcinoma of Lung Carcinoma Carcinoma, Non-Small-Cell Lung Head and Neck Neoplasms Head and Neck Neoplasms Lung Neoplasms Lung Neoplasms Small Cell Lung Carcinoma Stomach Neoplasms Stomach Neoplasms Stomach Neoplasms Uterine Cervical Neoplasms Uterine Cervical Neoplasms Adenocarcinoma Biliary Tract Neoplasms

ATC Classification

L01BA04

pemetrexed

Level 1: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS

Level 2: ANTINEOPLASTIC AGENTS

Activity Summary

IC50 229 meas. best 8.31

Ki 25 meas. best 8.89

Kd 1 meas. best 4.77

Target Activity Profile

Target	Type	Best pChEMBL	Mean pChEMBL	Best (nM)	# Data
Thymidylate synthase CHEMBL1952	Ki	8.89	8.0833	1.3	3
R2 CHEMBL614385	IC50	8.31	7.0289	4.9	9
Dihydrofolate reductase CHEMBL202	Ki	8.15	8.1433	7.0	3
Proton-coupled folate transporter CHEMBL1795188	IC50	8.08	7.778	8.3	5
KB CHEMBL398	IC50	8.0	7.015	9.9	18
Unchecked CHEMBL612545	IC50	7.93	6.2124	11.7	25
Trifunctional purine biosynthetic protein adenosine-3 CHEMBL3972	IC50	7.93	7.6275	11.7	4
CHO CHEMBL613853	IC50	7.88	7.078	13.2	5
CCRF-CEM CHEMBL382	IC50	7.8	7.8	16.0	1
NON-PROTEIN TARGET CHEMBL3879801	IC50	7.74	6.985	18.2	18
L1210 CHEMBL386	IC50	7.66	7.66	22.0	1
IGROV-1 CHEMBL613984	IC50	7.65	7.0711	22.2	9
Reduced folate transporter CHEMBL4833	IC50	7.62	7.156	23.8	5
A2780 CHEMBL614004	IC50	7.41	7.41	39.4	1
Folate receptor alpha CHEMBL2121	IC50	7.38	6.9967	42.0	6
Folate receptor beta CHEMBL5064	IC50	7.22	6.8167	60.0	6
Trifunctional purine biosynthetic protein adenosine-3 CHEMBL3972	Ki	7.19	6.178	65.0	5
Dihydrofolate reductase CHEMBL202	IC50	7.17	5.5112	68.0	17
Thymidylate synthase/GAR transformylase/AICAR transformylase CHEMBL3885528	IC50	7.16	7.16	70.0	1
A549 CHEMBL392	IC50	7.1	6.012	80.0	5
SW-620 CHEMBL612262	IC50	7.1	7.075	80.2	2
Proton-coupled folate transporter CHEMBL1795188	Ki	7.03	6.57	94.0	7
Thymidylate synthase CHEMBL1952	IC50	6.69	5.0318	204.0	22
Thymidylate synthase CHEMBL3160	Ki	6.47	6.47	340.0	1
Bifunctional dihydrofolate reductase-thymidylate synthase CHEMBL2425	IC50	6.37	5.8513	430.0	15
Thymidylate synthase CHEMBL5328	Ki	6.26	6.26	550.0	1
Dihydrofolate reductase CHEMBL4564	Ki	6.25	6.25	560.0	1
MCF7 CHEMBL387	IC50	6.19	6.19	650.0	1
Bifunctional purine biosynthesis protein ATIC CHEMBL2518	Ki	6.06	6.06	880.0	1
ADMET CHEMBL612558	IC50	6.05	6.02	894.0	4
Thymidylate synthase CHEMBL6137	IC50	5.96	4.364	1100.0	10
HepG2 CHEMBL395	IC50	5.9	5.9	1260.0	1
HUVEC CHEMBL613979	IC50	5.76	5.76	1730.0	1
NCI-H1975 CHEMBL614348	IC50	5.67	5.67	2130.0	1
Dihydrofolate reductase CHEMBL1809	IC50	5.64	5.64	2300.0	1
Dihydrofolate reductase CHEMBL2902	IC50	5.64	5.64	2300.0	1
MDA-MB-231 CHEMBL400	IC50	5.42	5.42	3850.0	1
Calu-1 CHEMBL613505	IC50	5.29	5.29	5120.0	1
OVCAR-3 CHEMBL614213	IC50	5.16	5.16	6900.0	1
SGC-7901 CHEMBL614909	IC50	5.04	5.04	9080.0	1
Thymidylate synthase CHEMBL2555	IC50	4.82	4.82	15000.0	1
Serine hydroxymethyltransferase, cytosolic CHEMBL1772927	Kd	4.77	4.77	16900.0	1
Serine hydroxymethyltransferase, cytosolic CHEMBL1772927	Ki	4.72	4.6	19100.0	2
Thymidylate synthase CHEMBL5328	IC50	4.7	4.56	20000.0	4
Thymidylate synthase CHEMBL4341	IC50	4.7	4.7	20000.0	1
Thymidylate synthase (EC 2.1.1.45) (TS) (TSase) CHEMBL1795153	IC50	4.12	4.12	76000.0	1

Pharmacokinetic Data

Parameter	Value	Units	Species
CL	0.01104	mL.min-1.g-1	Mus musculus
T1/2	0.65	hr	Mus musculus
Vd	0.62	ml	Mus musculus

Activity Data Samples

Top measurements by pChEMBL value

Target	Type	Rel.	Value	Units	pChEMBL	Assay	PubMed
Thymidylate synthase	Ki	=	1.3	nM	8.89	Inhibition of thymine synthase	20527892
Thymidylate synthase	Ki	=	1.3	nM	8.89	Inhibition of thymidylate synthase (unknown origin) assessed as inhibition const...	33540357
R2	IC50	=	4.94	nM	8.31	Antiproliferative activity against chinese hamster R2 cells expressing human PCF...	21879757
Dihydrofolate reductase	Ki	=	7.0	nM	8.15	Inhibition of recombinant human dihydrofolate reductase done at 37 degree C in p...	16078850
Dihydrofolate reductase	Ki	=	7.2	nM	8.14	Inhibition of DHFR	20527892
Dihydrofolate reductase	Ki	=	7.2	nM	8.14	Inhibition of DHFR (unknown origin) assessed as inhibition constant	33540357
Proton-coupled folate transporter	IC50	=	8.3	nM	8.08	Binding affinity to human PCFT expressed in Chinese hamster R2/PCFT4 cells asses...	29701475
KB	IC50	=	9.95	nM	8.0	Antiproliferative activity against human KB cells assessed as cell growth inhibi...	38116433
KB	IC50	=	9.94	nM	8.0	Cytotoxicity against human KB cells expressing human RFC/FRalpha/PCFT after 96 h...	24256410
Trifunctional purine biosynthetic protein adenosine-3	IC50	=	11.74	nM	7.93	Inhibition of GARFTase in human KB cells expressing RFC/FRalpha/PCFT assessed as...	25602637
Unchecked	IC50	=	11.74	nM	7.93	Inhibition of GARFTase in human KB cells assessed as incorporation of [14C]-glyc...	24256410
Proton-coupled folate transporter	IC50	=	13.2	nM	7.88	Inhibition of PCFT (unknown origin) expressed in Chinese hamster R2/PCFT4 cells ...	25234128
R2	IC50	=	13.2	nM	7.88	Antiproliferative activity against chinese hamster R2 cells expressing human PCF...	21879757
R2	IC50	=	13.2	nM	7.88	Growth inhibition of Chinese hamster R2 cells expressing human PCFT4 after 96 hr...	24111942
CHO	IC50	=	13.2	nM	7.88	Antitumor activity against CHO cells expressing PCFT (R2/PCFT4) transporter asse...	37582241
Proton-coupled folate transporter	IC50	=	13.2	nM	7.88	Binding affinity to human PCFT expressed in Chinese hamster R2/PCFT4 cells asses...	25602637
Proton-coupled folate transporter	IC50	=	13.2	nM	7.88	Binding affinity to human PCFT expressed in Chinese hamster R2/PCFT4 cells asses...	29425443
Unchecked	IC50	=	13.2	nM	7.88	Inhibition of DHFR in Chinese Hamster MTXRII-OuaR2-4 R2 cells expressing human P...	32503687
Unchecked	IC50	=	14.01	nM	7.85	Antiproliferative activity against chinese hamster RT-16 cells expressing human ...	38116433
CCRF-CEM	IC50	=	16.0	nM	7.8	Compound was evaluated for the half-maximal inhibition against human CCRF-CEM ly...	1447744

Literature References

PubMed	DOI	Target Context	# Activities
23297298	10.1124/dmd.112.049254	Mus musculus	15
22194678	10.1371/journal.pcbi.1002310	Hepatotoxicity	14
24256410	10.1021/jm401328u	KB	14
15646539	10.1016/s0399-8320(04)95062-2	Unchecked	11
31200235	10.1016/j.ejmech.2019.06.013	KB	9
38116433	10.1021/acsmedchemlett.3c00326	Unchecked	9
15646539	10.1016/s0399-8320(04)95062-2	NON-PROTEIN TARGET	8
21879757	10.1021/jm200739e	R2	8
28830032	10.1016/j.ejmech.2017.08.032	KB	7
29701475	10.1021/acs.jmedchem.8b00408	IGROV-1	7
29701475	10.1021/acs.jmedchem.8b00408	Proton-coupled folate transporter	6
32503687	10.1016/j.bmc.2020.115544	Dihydrofolate reductase	6
29807332	10.1016/j.ejmech.2018.05.020	A549	6
26317331	10.1021/acs.jmedchem.5b00801	Proton-coupled folate transporter	6
29425443	10.1021/acs.jmedchem.7b01708	Proton-coupled folate transporter	6
18680275	10.1021/jm8003366	NON-PROTEIN TARGET	5
24111942	10.1021/jm401139z	NON-PROTEIN TARGET	5
37582241	10.1021/acs.jmedchem.3c00763	CHO	5
21879757	10.1021/jm200739e	NON-PROTEIN TARGET	5
23297298	10.1124/dmd.112.049254	ADMET	5

Data from ChEMBL 36 via Core Engine