Skip to main content
Free research Free research Free compound review with research home and workspace preview
Quick search ChEMBL 36
Compound Detail

CHEMBL225071

RALTITREXED
💊 Approved Drug
Enter ChEMBL ID:
Free Research Context This compound will appear in recent viewed items on the research home for this browser.
Research home View demo workspace
💊 Approved Drug
Cc1nc(=O)c2cc(CN(C)c3ccc(C(=O)N[C@@H](CCC(=O)O)C(=O)O)s3)ccc2[nH]1

Basic Information

ChEMBL ID CHEMBL225071
Name RALTITREXED
Phase Approved
Structure Type MOL
InChI Key IVTVGDXNLFLDRM-HNNXBMFYSA-N
Therapeutic ✓ Yes

Known Names

Raltitrexed Tomudex ZD-16 ZD-1694 ZD1694
31
Targets
107
Activities
3
Assay Types
0
PK Parameters
20
Publications
5
Known Names
17
Indications
1
Mechanisms

Molecular Properties

458.5
MW (Da)
1.98
ALogP
7
HBA
4
HBD
152.7
PSA (Ų)
0.38
QED
0
Ro5 Violations
9
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 1996
Availability Unknown
Chirality Single Enantiomer

Routes of Administration

Parenteral

Flags

Natural Product
USAN Stem -trexed
USAN Year 1996

Extended Properties

Molecular Formula C21H22N4O6S
MW 458.50
Aromatic Rings 3
Heavy Atoms 32
NP-Likeness -0.78

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Thymidylate synthase inhibitor INHIBITOR Thymidylate synthase

Indications

Neoplasms Carcinoma, Hepatocellular Carcinoma, Squamous Cell Colorectal Neoplasms Colorectal Neoplasms Colorectal Neoplasms Colorectal Neoplasms Liver Neoplasms Mesothelioma Adenoma, Bile Duct Esophageal Neoplasms Esophageal Neoplasms Nasopharyngeal Carcinoma Pancreatic Neoplasms Rectal Neoplasms Stomach Neoplasms Precursor Cell Lymphoblastic Leukemia-Lymphoma

ATC Classification

L01BA03
raltitrexed
Level 1: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
Level 2: ANTINEOPLASTIC AGENTS

Activity Summary

IC50 105 meas. best 8.23
EC50 1 meas. best 6.72
Ki 1 meas. best 6.38

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
KB
CHEMBL398
IC50 8.23 7.945 5.9 10
Reduced folate transporter
CHEMBL4833
IC50 8.2 8.2 6.3 2
NON-PROTEIN TARGET
CHEMBL3879801
IC50 8.2 7.4525 6.3 12
L1210
CHEMBL386
IC50 8.15 7.4067 7.0 3
Thymidylate synthase
CHEMBL1952
IC50 8.05 6.2644 9.0 18
Dihydrofolate reductase
CHEMBL202
IC50 8.05 5.8033 9.0 3
IGROV-1
CHEMBL613984
IC50 7.9 7.8 12.6 4
Folate receptor alpha
CHEMBL2121
IC50 7.82 7.82 15.0 2
Unchecked
CHEMBL612545
IC50 7.82 6.12 15.0 8
Folate receptor beta
CHEMBL5064
IC50 7.66 6.895 22.0 4
HCT-116
CHEMBL394
IC50 7.12 7.12 76.0 1
Proton-coupled folate transporter
CHEMBL1795188
IC50 7.0 7.0 99.5 2
R2
CHEMBL614385
IC50 7.0 7.0 99.5 3
Histone-lysine N-methyltransferase EHMT2
CHEMBL6032
IC50 6.92 6.92 120.0 1
BJ
CHEMBL614358
EC50 6.72 6.72 192.0 1
Thymidylate synthase
CHEMBL3160
Ki 6.38 6.38 418.0 1
Bifunctional dihydrofolate reductase-thymidylate synthase
CHEMBL2425
IC50 6.32 5.94 480.0 5
Thymidylate synthase
CHEMBL3160
IC50 6.17 6.17 670.0 2
L1210 (1565)
CHEMBL614000
IC50 6.12 6.12 760.0 1
A549
CHEMBL392
IC50 6.09 6.09 810.0 1
Thymidylate synthase
CHEMBL4341
IC50 6.05 6.05 900.0 1
HepG2
CHEMBL395
IC50 5.89 5.455 1300.0 2
Thymidylate synthase
CHEMBL2555
IC50 5.64 5.64 2300.0 1
A-375
CHEMBL613859
IC50 5.33 5.33 4680.0 1
Thymidylate synthase
CHEMBL6137
IC50 5.28 5.0343 5300.0 7
HeLa
CHEMBL399
IC50 5.26 5.26 5510.0 1
Thymidylate synthase
CHEMBL5328
IC50 5.1 5.0867 8000.0 3
SGC-7901
CHEMBL614909
IC50 5.06 5.06 8700.0 1
MGC-803
CHEMBL3706566
IC50 5.02 5.02 9520.0 1
MCF7
CHEMBL387
IC50 4.96 4.93 10900.0 2
Dihydrofolate reductase
CHEMBL1809
IC50 4.64 4.64 23000.0 2
L1210 (RD1694)
CHEMBL614713
IC50 4.02 4.02 95000.0 1

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
KB IC50 = 5.9 nM 8.23 Antiproliferative activity against human RFC and FRalpha expressing human KB cel... 18680275
KB IC50 = 5.9 nM 8.23 Antiproliferative activity against human KB cells expressing human RFC, FRalpha ... 21879757
KB IC50 = 5.9 nM 8.23 Growth inhibition of human KB cells expressing human RFC/FRalpha/PCFT after 96 h... 24111942
KB IC50 = 5.9 nM 8.23 Cytotoxicity against human KB cells assessed as cell growth inhibition incubated... 25234128
KB IC50 = 5.9 nM 8.23 Antiproliferative activity against human KB cells expressing human RFC/FR-alpha/... 29425443
NON-PROTEIN TARGET IC50 = 6.3 nM 8.2 Antiproliferative activity against human RFC expressing Chinese hamster PC43-10 ... 18680275
NON-PROTEIN TARGET IC50 = 6.3 nM 8.2 Antiproliferative activity against chinese hamster PC43-10 expressing human RFC ... 21879757
NON-PROTEIN TARGET IC50 = 6.3 nM 8.2 Growth inhibition of Chinese hamster PC43-10 cells after 96 hrs by CellTiter-blu... 24111942
Reduced folate transporter IC50 = 6.3 nM 8.2 Inhibition of RFC (unknown origin) expressed in Chinese hamster PC43-10 cells as... 25234128
Reduced folate transporter IC50 = 6.3 nM 8.2 Binding affinity to human RFC expressed in Chinese hamster PC43-10 cells assesse... 29425443
L1210 IC50 = 7.0 nM 8.15 Tested for the concentration to inhibit 50% of L1210 cell growth in culture. 2066994
L1210 IC50 = 9.0 nM 8.05 Growth inhibition of murine tumor L1210 cell line 10508430
Dihydrofolate reductase IC50 = 9.0 nM 8.05 Inhibition of DHFR (unknown origin) 33243532
Thymidylate synthase IC50 = 9.0 nM 8.05 Inhibition of Thymidylate synthase (unknown origin) 33243532
IGROV-1 IC50 = 12.6 nM 7.9 Antiproliferative activity against human RFC and FRalpha expressing human IGROV1... 18680275
IGROV-1 IC50 = 12.6 nM 7.9 Antiproliferative activity against human IGROV1 cells expressing human RFC, FRal... 21879757
Folate receptor alpha IC50 = 15.0 nM 7.82 Binding affinity to human FR-alpha receptor expressed in Chinese hamster RT16 ce... 29425443
Unchecked IC50 = 15.0 nM 7.82 Cytotoxicity in RFC-null Chinese hamster R2 cells assessed as reduction in cell ... 29425443
NON-PROTEIN TARGET IC50 = 15.0 nM 7.82 Antiproliferative activity against human FRalpha expressing Chinese hamster RT16... 18680275
Unchecked IC50 = 15.0 nM 7.82 Cytotoxicity in RFC-null Chinese hamster R2 cells assessed as reduction in cell ... 27458733

Literature References

PubMed DOI Target Context # Activities
22194678 10.1371/journal.pcbi.1002310 Hepatotoxicity 14
15646539 10.1016/s0399-8320(04)95062-2 Unchecked 11
15646539 10.1016/s0399-8320(04)95062-2 NON-PROTEIN TARGET 8
- 10.6019/CHEMBL4495565 SARS-CoV-2 6
24111942 10.1021/jm401139z NON-PROTEIN TARGET 5
8917644 10.1021/jm960097t Thymidylate synthase 5
21879757 10.1021/jm200739e NON-PROTEIN TARGET 5
18680275 10.1021/jm8003366 NON-PROTEIN TARGET 5
18680275 10.1021/jm8003366 KB 4
11052789 10.1021/jm000200l Thymidylate synthase 4
11052789 10.1021/jm000200l CCRF-CEM 4
11052789 10.1021/jm000200l Unchecked 4
20014752 10.1021/tx900326k Hepatotoxicity 3
- 10.6019/CHEMBL4495564 Replicase polyprotein 1ab 3
12570380 10.1021/jm0203534 Thymidylate synthase 3
20056546 10.1016/j.bmc.2009.11.029 Dihydrofolate reductase 2
15837298 10.1016/j.bmcl.2005.03.029 Thymidylate synthase 2
20056546 10.1016/j.bmc.2009.11.029 Bifunctional dihydrofolate reductase-thymidylate synthase 2
10508430 10.1021/jm9803727 L1210 (1565) 2
15615522 10.1021/jm040144e Dihydrofolate reductase 2

Data from ChEMBL 36 via Core Engine