Polymerases are enzymes that are vitally important for the synthesis of nucleic acid polymers. Polymerases participate in DNA metabolism, modulating different processes, in particular, mitosis, damage repair, transcription, and replication [1]. Therefore, the family of these essential proteins can be a valuable target for drug development and treatment of many diseases, primarily of bacterial and viral nature, as well as different cancers [1-4]. For instance, DNA Polymerases and Reverse Transcriptases serve as molecular targets for antiviral and antitumor chemotherapy.
With these considerations in mind, Life Chemicals has designed its brand-new polymerase-focused Screening Sets to be used in modern drug discovery projects:
- Polymerase Focused Library – Similarity to ChEMBL Database
- Polymerase Focused Library – 15 polymerase assays
- DNA Polymerase Targeted Library
The compound selection can be customized based on your requirements, cherry picking is available.
Please, contact us at orders@lifechemicals.com for any additional information and price quotations.

Polymerase Focused Library – Similarity to ChEMBL Database
Over 1,200 drug-like screening compounds were selected using a 2D fingerprint similarity search (Tanimoto index > 85 %) against a reference set of 20,000 compounds from the ChEMBL database with reported activity against polymerase targets:
- DNA polymerase beta
- DNA polymerase iota
- DNA polymerase eta
- Poly [ADP-ribose]polymerase-1
Polymerase Focused Library – 15 polymerase assays
More than 17,000 structurally-diverse molecules with potential polymerase inhibition activity were picked out for this screening set.
First, a reference set of 4,567 biologically active compounds was prepared based on 15 polymerase-focused assays, using the data available from patents and literature publications. Targeted were the following polymerases:
- RNA polymerase beta subunit (EC 2.7.7.6)
- Ribonuclease HI (RNase HI) (Ribonuclease H) (RNase H)
- DNA Polymerase III Holoenzyme
- Measles Virus RNA-Dependent RNA Polymerase
- Reverse Transcriptases (HIV-1, HIV-2, West Nile Virus NS2bNS3)
The Life Chemicals HTS Compound Collection has then been searched for small-molecule analogs of the polymerase inhibitors from a reference set, using the MDL public keys and the Tanimoto similarity cut-off 90 %. The resulting compounds were arranged according to their similarity vs. the reference set and predicted polymerase activity, putting the most active compounds at the top of the list.
DNA Polymerase Targeted Library
Using pharmacophore hypothesis-driven screening, our chemoinformatics team has developed a library of over 600 unique structurally diverse screening compounds for the following DNA polymerase-related drug targets:
Figure 1. Replication of human herpes virus DNA is catalyzed by DNA polymerase. The presented compounds can inhibit this process by acting on the viral enzyme.
Human DNA polymerase alpha (POLA1)
Human DNA polymerase alpha catalytic subunit, also known as POLA1, is an enzyme that plays a crucial role in DNA replication. It is responsible for the synthesis of the RNA-DNA primers that are essential for the initiation of DNA synthesis. POLA1 is a member of the DNA polymerase family, which consists of enzymes that are involved in DNA replication, repair, and recombination [5]. POLA1 plays an important role in preventing DNA damage, and disorders in the functioning or synthesis of this protein can lead to congenital pathologies, such as growth retardation, microcephaly, hypogonadism, and cancer [6]. POLA1 also affects the regulation of chromosome telomere length, preventing premature cellular aging [7]. Further research on this enzyme and its role in cellular processes could lead to the development of new therapeutic approaches for a variety of diseases, especially cancer.
Key features:
- Method: high-throughput virtual screening (pharmacophore hypothesis)
- X-Ray data used: 4Q5V
- Filters used: QikProp properties and descriptors
- Number of compounds selected: 326
Figure 2. The pharmacophore hypothesis by 4Q5V and examples of lead compounds.
Human herpesvirus 1 DNA polymerase
Human herpesvirus 1 (HHV-1) is a member of the herpesvirus family that causes cold sores and other infections in humans [8]. The virus encodes a catalytic subunit of DNA polymerase, which plays an important role in the replication of the viral genome. HHV-1 DNA polymerase catalyzes the addition of nucleotides to the growing DNA strand during viral genome replication [9], thus inhibitors of this enzyme can be used as antiviral agents [10]. Also, human herpesvirus 1 can lead to serious illnesses, such as herpes simplex encephalitis, which leads to the production and accumulation of biomarkers of Alzheimer's disease [11]. The catalytic subunit of HHV-1 DNA polymerase is also involved in the regulation of the body's immune response to viral infection [12]. Overall, the study of the HHV-1 DNA polymerase catalytic subunit has provided important insights into the mechanisms of viral replication and pathogenesis. Further research on this enzyme and its role in viral infection could lead to the development of new therapeutic approaches for the treatment of HHV-1 infections.
Key features:
- Method: high-throughput virtual screening (pharmacophore hypothesis)
- X-Ray data used: 7LUF
- Filters used: QikProp properties and descriptors
- Number of compounds selected: 302
Figure 3. The pharmacophore hypothesis by 7LUF and examples of lead compounds.
References:
- Garro HA, Pungitore CR. Coumarins as Potential Inhibitors of DNA Polymerases and Reverse Transcriptases. Searching New Antiretroviral and Antitumoral Drugs. Curr Drug Discov Technol. 2015;12(2):66-79. doi: 10.2174/1570163812666150716111719.
- Velkov T, Carbone V, Akter J, Sivanesan S, Li J, Beddoe T, Marsh GA. The RNA-dependent-RNA polymerase, an emerging antiviral drug target for the Hendra virus. Curr Drug Targets. 2014 Jan;15(1):103-13. doi: 10.2174/1389450114888131204163210. PMID: 24102407.
- Jiang Y, Yin W, Xu HE. RNA-dependent RNA polymerase: Structure, mechanism, and drug discovery for COVID-19. Biochem Biophys Res Commun. 2020 Sep 4:S0006-291X(20)31721-6. doi 10.1016/j.bbrc.2020.08.116. Epub ahead of print. PMID: 32943188; PMCID: PMC7473028.
- Wang J, Li H, He G, Chu Z, Peng K, Ge Y, Zhu Q, Xu Y. Discovery of Novel Dual Poly(ADP-ribose)polymerase and Phosphoinositide 3-Kinase Inhibitors as a Promising Strategy for Cancer Therapy. J Med Chem. 2020 Jan 9;63(1):122-139. doi: 10.1021/acs.jmedchem.9b00622. Epub 2019 Dec 27. PMID: 31846325.
- Baranovskiy AG, Babayeva ND, Zhang Y, et al. Mechanism of Concerted RNA-DNA Primer Synthesis by the Human Primosome. J Biol Chem. 2016;291(19):10006-10020. doi:10.1074/jbc.M116.717405
- Van Esch H, Colnaghi R, Freson K, et al. Defective DNA Polymerase α-Primase Leads to X-Linked Intellectual Disability Associated with Severe Growth Retardation, Microcephaly, and Hypogonadism. Am J Hum Genet. 2019;104(5):957-967. doi:10.1016/j.ajhg.2019.03.006
- Cai SW, Zinder JC, Svetlov V, et al. Cryo-EM structure of the human CST-Polα/primase complex in a recruitment state. Nat Struct Mol Biol. 2022;29(8):813-819. doi:10.1038/s41594-022-00766-y
- Connolly SA, Jardetzky TS, Longnecker R. The structural basis of herpesvirus entry. Nat Rev Microbiol. 2021;19(2):110-121. doi:10.1038/s41579-020-00448-w
- Terrell SL, Pesola JM, Coen DM. Roles of conserved residues within the pre-NH2-terminal domain of herpes simplex virus 1 DNA polymerase in replication and latency in mice. J Gen Virol. 2014;95(Pt 4):940-947. doi:10.1099/vir.0.061903-0
- Vashishtha AK, Kuchta RD. Effects of Acyclovir, Foscarnet, and Ribonucleotides on Herpes Simplex Virus-1 DNA Polymerase: Mechanistic Insights and a Novel Mechanism for Preventing Stable Incorporation of Ribonucleotides into DNA. Biochemistry. 2016;55(7):1168-1177. doi:10.1021/acs.biochem.6b00065
- Marcocci ME, Napoletani G, Protto V, et al. Herpes Simplex Virus-1 in the Brain: The Dark Side of a Sneaky Infection. Trends Microbiol. 2020;28(10):808-820. doi:10.1016/j.tim.2020.03.003
- Lawler JL, Coen DM. HSV-1 DNA polymerase 3'-5' exonuclease-deficient mutant D368A exhibits severely reduced viral DNA synthesis and polymerase expression. J Gen Virol. 2018;99(10):1432-1437. doi:10.1099/jgv.0.001138