Anticancer Library

Cancer is a generic term for a large group of diseases that arise from the transformation of normal cells into malignant tumor cells. It is responsible for about 1 in 6 deaths and is the second leading cause of death globally [1]. Therefore, the search for novel chemotherapeutic treatments for cancer is one of the most acute problems of modern pharmacology [2-4].

The Life Chemicals Anticancer Screening Library comprises over 6,300 novel drug-like screening compounds with potential anti-tumor activity, targeting various cancer types, such as prostate and breast cancers, leukemia, lymphoma, carcinoma. It is designed as a useful tool for high throughput screening (HTS) in anticancer drug discovery research. The Library was prepared with similarity search methods against publicly available databases (ChEMBL and BindingDB) of molecules with reported antitumor activity.

The Life Chemicals HTS Compound Collection was first screened against 12,000 reference compounds with assigned activity values lower than 10 mM by similarity search and with 80 % similarity cut-off (Tanimoto) and PAINS / reactive group filtration to provide a collection of 1,500 structurally diverse compounds with potential inhibitory activity against the following cancer cell lines* for cell-based phenotypic screening projects:

3LL
A253
A-375
A549
AGS
B16-F10
BC1
Bel-7402
BGC-823
CCRF-CEM
CHRC5
DU-145
Fibrosarcoma cell line
HBL-100
HCC 2998
HCT-116
HeLa
Hepatoblastoma cell line
HepG2
HL-60
HNO 97

HONE1
HT-29
Human T-cell line
Jurkat
K562
KB
KU812
KYSE-150
KYSE-70
Leukemia 60 cell line
Lewis lung carcinoma cell line
LNCaP
LoVo
LOX IMVI
Lung cancer cell line
LXF-289
M14
MCF7
MDA-MB-231
Melanoma tumor cell line
MOLT-4

NCI/ADR-RES
NCI-H157
NCI-H2009
NCI-H460
NUGC-3
P388
Panel leukemia (Carcinoma cell lines)
Panel NCI-60 (60 carcinoma cell lines)
PC-3
SF-268
SF-295
SH-SY5Y
SK-MEL-5
SK-OV-3
T-24
T98G
THP-1
TK-10
U-937
UO-31

Then the HTS Compound Collection was filtered for analogues of molecules with known activity against different cancer-related targets, using the 80 % similarity cut-off (Tanimoto) on MDL public keys fingerprints. 

As a result, around 4,800 potential anti-cancer compounds were selected for the following targets*:

  • Anoctamin-1
  • ATP-binding cassette sub-family G member 2
  • Beta-hexosaminidase subunit beta
  • Breast cancer type 1 susceptibility protein
  • Bromodomain testis-specific protein
  • Cyclin-dependent kinase 2-associated protein 1
  • L-type amino acid transporter 3
  • Lysine-specific demethylase 5B
  • MAP kinase p38 alpha
  • Mitogen-activated protein kinase kinase kinase 8
  • Mixed lineage kinase 7
  • Nuclear receptor coactivator 3
  • PDZ-binding kinase
  • Serine/threonine-protein kinase WNK2

All PAINS, toxic, and reactive compounds are excluded from the Library, Ro5 compliance is indicated. All compounds are in stock, the Library is being updated continuously with newly-synthesized molecules.

Compound cherry-picking is available.

*The results could be traced back to the specific cell lines or single cancer targets (indicated in the column “Target type” within the corresponding SD file).

References

  1. https://www.who.int/news-room/fact-sheets/detail/cancer
  2. Ackova DG, Smilkov K, Bosnakovski D.Contemporary Formulations for Drug Delivery of Anticancer Bioactive Compounds // Recent Pat Anticancer Drug Discov. 2019;14(1):19-31.
  3. Geromichalos GD, Alifieris CE, Geromichalou EG, Trafalis DT. Overview on the current status of virtual high-throughput screening and combinatorial chemistry approaches in multi-target anticancer drug discovery; Part I // J BUON. 2016 Jul-Aug;21(4):764-779; Part II //J BUON. 2016;21(6):1337-1358.
  4. Hameed R, Khan A, Khan S, Perveen S. Computational Approaches Towards Kinases as Attractive Targets for Anticancer Drug Discovery and Development // Anticancer Agents Med Chem. 2019;19(5):592-598.