Síntese de DNA/RNA

HBV-IN-14: a pyridinopyrimidinone, potent cccDNA inhibitor for HBV study (patent WO2021190502A1, comp 5).

<p>6-Hydroxy-DOPA is an allosteric inhibitor of RAD52, it inhibits proliferation of BRCA-deficient cancer cells in vitro and also inhibits APE1.</p>

D-I03 is a selective RAD52 inhibitor with a Kd of 25.8 µM.

RP-6685 is a potent, selective DNA Polθ inhibitor with strong oral efficacy, an IC50 of 5.8 nM, and marked antitumor effects in mice.

<p>Talviraline (Bay 10-8979) is an RNA-induced DNA polymerase inhibitor.Talviraline is a potent inhibitor of HIV-1-induced cell killing and HIV-1 replication in a</p>

Caracemide (NSC-253272) inhibits the enzyme ribonucleotide reductase of Escherichia coli. Caracemide can be used in anticancer studies.

ZIM, from 4-Aminoantipyrine, induces DNA and chromosomal damage, cell death, and phagocytosis, with potential in cancer therapy.

DDRI-18 is an inhibitor that regulates the DNA damage response, has anticancer activity, and inhibits non-homologous end-joining (NHEJ) DNA repair.

<p>116-9e (MAL2-11B) is an Hsp70 chaperone DNAJA1 inhibitor with antiviral properties, inhibits SV40 replication, and can be used to study cancer drug resistance.</p>

<p>SMN-C2, a SMN2 gene splicing regulator, is an RNA-binding ligand that regulates pre-mRNA splicing and has potential for studying spinal muscular atrophy.</p>

<p>Cytembena is a cytostatic and a carcinogenic compound that may increase the incidence of fibroadenomas.Cytembena broadly inhibits DNA biosynthesis.</p>

Anticancer agent 73 inhibits TRBP, disrupting TRBP-Dicer, and hinders HCC growth and spread by altering HCC miRNA and protein expression.

<p>Galocitabine (Neofrutulon), a thymidylate synthase inhibitor, is used potentially for the treatment of cancer.</p>

<p>ERCC1-XPF-IN-2: Nucleotide repair active, boosts cisplatin, inhibits ERCC1-XPF (IC50: 0.6 μM).</p>

TTP-8307 is an antiviral compound that inhibits the replication of rhinoviruses and enteroviruses and is used in the study of viral infections.

<p>CHD1Li 6.11 inhibits CHD1L protein (IC50: 3.3 µM), shrinks CRC tumors in vivo, and is orally active.</p>

<p>KY386 is a potent and selective DHX33 helicase inhibitor with an IC50 value of 19 nM.</p>

<p>RNA polymerase II-IN-1 (19iv), an amatoxin, inhibits Pol II at 36.66 nM IC50, is more toxic to cancer cells, less to normal cells than α-Amanitin.</p>

<p>MC-VC-PAB-Cyclohexanediamine-Thailanstatin A is a spliceostatin analog and a drug-linker conjugate for antibody-drug conjugates (ADC), comprising the cytotoxic</p>

<p>COH1 is a ribonucleotide reductase (RR) inhibitor utilized in research pertaining to cancer, mitochondrial diseases, and neurodegenerative disorders [1].</p>

5,6,7,8-Tetrahydro-8-deazahomofolic acid is a potential thymidylate synthase (TS) inhibitor and other folate related enzymes inhibitor.

<p>8-NH2-ATP tetrasodium, an inactive ATP variant, originates from 8-NH2-Ado tetrasodium, which triggers the apoptosis-associated cleavage of poly (ADP-ribose) polymerase [1] [2].</p>

<p>WRN Inhibitor 4 (Example 107), a cyclic vinyl sulfone-based compound, serves as an inhibitor of the Werner Syndrome ATP-dependent helicase enzyme (WRN).</p>

DHX9-IN-6 is a highly effective ATP-dependent RNA helicase A (DHX9) inhibitor, used in cancer research.

<p>WRN Inhibitor 3 (example 110), a cyclic vinyl sulfone-based compound, serves as an inhibitor of the Werner Syndrome ATP-dependent helicase enzyme (WRN).</p>

<p>hDHODH-IN-1 is an inhibitor of human dihydroorotate dehydrogenase (hDHODH) with an anti-inflammatory effect.</p>

<p>3-Cyanovinylcarbazole phosphoramidite: an antiviral, hinders viral DNA synthesis, modifies ribonucleotides.</p>

Cytarabine 5′-monophosphate (ara-CMP), an active metabolite of the nucleoside analog cytarabine formed by deoxycytidine kinase, is incorporated into DNA by DNA polymerase α, significantly slowing DNA synthesis. It inhibits nuclear and mitochondrial DNA replication in S. cerevisiae at 15 mM and improves survival in an L1210 murine leukemia model at 3.5-75.1 mg/kg.

<p>TAS-114 is a dUTPase and DPD inhibitor that modulates catabolic pathways to improve systemic availability of 5-FU.</p>

Balapiravir HCl, an NS5B inhibitor, is used potentially for the treatment of HCV infection.

FAICAR (5-Formamidoimidazole-4-carboxamide ribotide), a purine nucleotide, plays a crucial role in metabolic processes.

GSPT1 degrader-2 is a potent degrader of GSPT1 [1].

<p>Votoplam functions as a gene splicing modulator, employed in the inhibition of Huntington's disease [1].</p>

<p>BVDU 5′-Triphosphate is an antiviral agent labeled with 5′-Triphosphate that specifically targets viral DNA polymerase.</p>

WRN Inhibitor 2 (example 118), a potent inhibitor of the WRN (Werner Syndrome ATP-dependent helicase enzyme), exhibits a pIC50 value of 7.0 or greater [1].

UNC-2170 (UNC2170 Maleate) is the methyl-lysine binding protein, 53BP1 ligand.

<p>H3B-968 is a potent inhibitor of Werner syndrome protein (WRN) with an IC50 of approximately 10 nM, effectively targeting its helicase, ATPase, and exonuclease</p>

<p>DHX9-IN-4 is an ATP-dependent RNA helicase DHX9 inhibitor used in cancer research.</p>

Diazoketone methotrexate is an analog of methotrexate with potential antitumor activity.

<p>DDD85646 is an inhibitor of T. brucei N-myristoyltransferase with a Ki of 1.44 nM, an IC50 of 2 nM and an EC50 of 2 nM. The IC50 of hNMT is 4 nM.</p>

DMA-IN-1 is a DNA adenine methyltransferase (DAM) inhibitor with an IC50 value of 48 μM.

Galidesivir hydrochloride is an inhibitor of viral RNA-dependent RNA polymerase (RdRp). It inhibits SARS-CoV-2 by tightly binding to its RdRp.

Amotosalen is a Dermatologic Agent.

pppApG serves as an initial substrate for the synthesis of vRNA (viral RNA) and cRNA (complementary RNA), with applications in influenza virus research [1].

DNA polymerase-IN-3 (Compd 5b), a coumarin derivative, demonstrates inhibitory activity against Taq DNA polymerase and has potential applications in

WRN Inhibitor 1 (example 7) is an inhibitor of the Werner Syndrome ATP-dependent helicase enzyme (WRN), selectively targeting its helicase domain.

Thymidine-5’-O-(α,β-methylene)diphosphate (TMP-CP), a hydrolytically stable derivative of TDP, functions as an inhibitor of thymidine kinase (Ki = 23 µM).

9-Deazaguanine is a nucleoside analogue exhibiting inhibitory activity against bovine purine nucleoside phosphorylase (PNP).

Emzadirib (RAD51-IN-2) is a potent RAD51 inhibitor with potential anticancer activity for the study of DNA damage repair.

RAD51-IN-4, a potent RAD51 inhibitor, may be useful in researching mitochondrial defect-related conditions.

<p>AVG-233 is an RNA-dependent RNA polymerase (RdRp) inhibitor with antiviral activity for the study of respiratory syncytial virus infections.</p>

Cytidine 3'-monophosphate, a ribonucleotide, results from the hydrolysis of cytidine 2',3'-cyclic monophosphate via RNase—a process that cytidine 3'-monophosphate itself inhibits. Additionally, it can be dephosphorylated to cytidine by 3'-nucleotidase.

CCT239065 is a novel, selective, and efficacious nanomolar pyridopyrazinone V600EBRAF and LCK inhibitor.

5,11-methenyltetrahydrohomofolate blocks GAR & AIR transformylase; used as an anti-purine drug.

(±)9(10)-DiHOME, the diol derivative of (±)9(10)-EpOME—a cytochrome P450-derived epoxide of linoleic acid also known as leukotoxin—is formed through the action of soluble epoxide hydrolase (sEH) in neutrophils. It exhibits toxicity towards Sf21 cells expressing sEH as well as tolacZ-expressing control cells, differing from leukotoxin which only harms sEH-containing cells. Furthermore, combined exposure to 9(10)- and 12(13)-DiHOME leads to cell death in rabbit renal proximal tubule cells by disrupting mitochondrial respiration, and causes lung injury, respiratory distress, and mortality in mice, highlighting its role as a toxic lipid mediator. Specifically, 9(10)-DiHOME has been associated with acute respiratory distress syndrome (ARDS), a severe and often deadly complication in patients with major burns. Elevated levels of this compound have been detected in the bronchoalveolar lavage fluid (BALF) of women, but not men, with chronic obstructive pulmonary disease (COPD), and its levels are also increased in patients with allergic asthma, indicating its significance in respiratory conditions.

<p>WRN Inhibitor 5 (Example 157), a cyclic vinyl sulfone-based compound, serves as an inhibitor of Werner Syndrome ATP-dependent helicase enzyme (WRN).</p>

Pen is an oral cancer drug that blocks DNA synthesis by inhibiting key enzymes and integrating into DNA.

<p>53BP1-binding protein 1 (53BP1) engages with dimethylated lysine 20 on histone 4 (H4K20me2) through its tandem tudor domains within a homodimer configuration, crucial for the DNA damage response. UNC2170, a micromolar 53BP1 ligand, selectively interacts with this site, demonstrating at least 17-fold preference for 53BP1 over similar proteins. This interaction occurs in a pocket formed by the 53BP1's tudor domains. Moreover, UNC2170 acts as an antagonist to 53BP1 in cellular lysates, effectively inhibiting class switch recombination, a process dependent on the functional 53BP1 tudor domain, thus confirming its cellular activity.</p>

Abetimus (LJP 394 free base), an immunosuppressant composed of four double-stranded DNA (dsDNA) oligonucleotides, can crosslink anti-dsDNA antibodies on B cell

MOMA-341 is a highly selective inhibitor targeting the Werner RecQ-like helicase (WRN). It exerts a dual mechanism of allosteric regulation and ATP competitive inhibition by binding to the cysteine 727 site of the WRN protein. In mouse models with mismatch repair deficiency (dMMR) or high microsatellite instability (MSI-H), MOMA-341 can induce DNA damage, cell apoptosis, and promote tumor shrinkage. This compound exhibits significant anti-tumor activity and has potential application prospects in the study of advanced and metastatic solid tumors.

12R-LOX-IN-1 (Compound 4a), with an IC50 of 28.25 µM, is an inhibitor of 12R-LOX.

<p>G4/HDAC-IN-1, a G4/HDAC dual inhibitor, IC50 1.1 µM, blocks TNBC growth, useful in cancer research.</p>

8-Azahypoxanthine (NSC-22709) inhibits hypoxanthine-guanine-xanthine phosphoribosyltransferase and has antimalarial properties.

PD 121373, a Benzothiopyrano-indazole, inhibits nucleic acid synthesis, equally affecting DNA/RNA.

NSC15520 is an RPA inhibitor that inhibits helical destabilization of double-stranded DNA oligonucleotides and can be used to study DNA damage repair.

NVS-SM2 boosts SMN2 splicing, enhances exon 7 inclusion, and raises SMN protein levels orally.

<p>Thymectacin (NB 1011) is a selective thymidine synthase (TS) inhibitor with anticancer activity for the study of colon cancer and solid tumors.</p>

<p>SMN-C3 (MV8T2MCK57) is an orally active modulator of SMN2 splicing, and has the potential to treat spinal muscular atrophy (SMA).</p>

<p>DHX9-IN-2 is an inhibitor targeting ATP-dependent RNA de-helicase A (DHX9) with anticancer and antitumor activity for cancer research.</p>

LNA-Adenosine (LNA-A) is a nucleoside analogue that acts as a ligand for adenosine A3 receptors.

CeMMEC1 is an inhibitor of BRD4, and also has a great affinity for TAF1(IC50=0.9 μM).

<p>Lomibuvir (VCH-222, VX-222) is an allosteric inhibitor of HCV NS5B with Kd 17 nM, blocks RNA elongation, EC50 5.2 nM for 1b/Con1.</p>

<p>Sorivudine (BV-araU) is an antiviral blocking DNA synthesis in viruses like varicella, HSV-1, and Epstein-Barr.</p>

<p>WRN inhibitor 7 (Compound h6), a potent inhibitor of Werner syndrome helicase, demonstrates effective suppression of WRN's helicase and ATPase activities with IC50 values of 9.8 μM and 15.8 μM, respectively. This compound is utilized in the study of microsatellite instable (MSI) cancers [1].</p>

<p>Ladirubicin, as an anthracyclines analog is the leading compound of alkylcyclines.</p>

<p>2'-(2-Nitrobenzyl)-ATP is an analog of rATP. It acts as a transcription terminator by inhibiting the elongation of RNA chains by T7 RNA polymerase.</p>

<p>LN-439A (compound LN-439A) is a novel BAP1 inhibitor that suppresses the growth of basal-like breast cancer by degrading KLF5.</p>

<p>2,5-Di-tert-butyl-1,4-benzoquinone is a potent antibacterial agent found primarily in marine Streptomyces sp. VITVSK1, effective against emerging antibiotic resistance. Additionally, it serves as a powerful inhibitor of RNA polymerase.</p>

<p>And1 degrader 1 (Compound A15) is a degrader of acidic nucleoplasmic DNA-binding protein 1 (And1) that notably induces degradation of And1 in NSCLC cells. When combined with Olaparib (1 μM), And1 degrader 1 at a concentration of 5 μM effectively inhibits proliferation in A549 and H460 cells. This compound is applicable in cancer research studies.</p>

<p>KL-50, a selective toxin, effectively targets tumors deficient in the DNA repair protein O6-methylguanine-DNA-methyltransferase (MGMT), which corrects O6-alkylguanine lesions. This compound induces both DNA damage response pathways and cell cycle arrest in MGMT-deficient cells, regardless of mismatch repair (MMR) status. KL-50 shows promise in the study of brain tumors lacking MGMT.</p>

<p>AB25583 is a small molecule inhibitor of Polθ helicase (Polθ-hel) with an IC50 of 6 nM. It selectively kills cells deficient in BRCA1/2 and synergizes with Olaparib in cancer cells harboring pathogenic BRCA1/2 mutations. AB25583 can be utilized in tumor research.</p>

<p>GHP-88309 is an orally active, broad-spectrum anti-paramyxovirus agent that targets viral polymerase, interrupting viral RNA synthesis. It effectively inhibits respiratory syncytial virus (RSV), measles virus (MeV), and canine distemper virus (CDV) with an EC50 of 0.06-1.2 μM. In mouse models, GHP-88309 demonstrates significant anti-infective activity.</p>

<p>VPC-80051 is an hnRNP A1 splicing activity inhibitor that directly interacts with the hnRNP A1 RBD and reduces AR-V7 messenger levels in the 22Rv1 CRPC cell line. VPC-80051 is applicable in prostate cancer research.</p>

<p>5-Methylcytosine hydrochloride plays a critical role in regulating gene expression, promoting genomic imprinting, and inhibiting transposon factors. It is also closely associated with translation fidelity and tRNA recognition.</p>

<p>Xanthosine-5'-Triphosphate (5'-XTP) trisodium is a nucleotide formed through the deamination of purine bases. It serves as a substrate for inosine triphosphate pyrophosphatase (ITPase).</p>

(R)-CSN5i-3 is CSN5i-3 of the R configuration.

<p>Epolactaene: neuritogenic, inhibits mammalian DNA polymerases &amp; human DNA topoisomerase II.</p>

<p>UMPK ligand 1 (ZINC07785412) serves as a ligand for uridine monophosphate kinase (UMPK).</p>

<p>(E)-Antiviral agent 67 (compound PC6) is a pyrazolone-based antiviral compound that exhibits inhibitory activity against RNA-dependent RNA polymerase.</p>

<p>DHX9-IN-19 (compound 3) is an orally active inhibitor of DHX9, playing a significant role in cancer research.</p>

<p>Dencatistat is a highly selective and oral cytidine triphosphate synthase 1 CTPS1 inhibitor specific.CTPS1-IN-2 for B-cell, T-cell lymphomas and solid tumors.</p>

<p>DNA ligase-IN-2 (compound 2) acts as a potent LigA inhibitor, effectively hindering the DNA-independent spontaneous adenylation activity of full-length LigA and the truncated enzyme LigA:AD with an IC50 of 29 nM. It also significantly suppresses the in vitro growth of Staphylococcus aureus, showing MIC values of 1 μg/mL for S. aureus ATCC 29213 and S. aureus ATCC 700699, while the MIC for Escherichia coli (E. coli) ATCC 25922 is &gt;64 μg/mL.</p>

Plevitrexed, an oral TS inhibitor (Ki: 0.44 nM), targets α-folate receptor & reduced folate carrier, treats gastric cancer.

<p>RAD51-IN-8 inhibits RAD51-BRCA2 interaction and H4A4 with EC50 of 19 μM; a micromolar PPI inhibitor.</p>

<p>RECTAS-2.0 is a small molecule designed to correct RNA mis-splicing caused by the GLA c.639+919G&gt;A mutation, intended for research in Fabry disease.</p>

3'-NH-Tr-2',3'-DMF-ddA-5'-CE-Phosphoramidite serves as a precursor of adenosine nucleotide monomers used in the solid-phase synthesis of oligonucleotides, particularly for modifying oligonucleotides such as terminally modified DNA strands. It features Trityl (Tr), Cyanoethyl (CE), and Dimethylformamidine (DMF) protective groups, classifying it as a ddNTP adenosine nucleoside suitable for applications like oligonucleotide solid-phase synthesis, probe design, and chain termination sequencing.

3′-Amino-2′,3′-dideoxy-CTP is an analog of nucleoside triphosphates. It selectively inhibits DNA polymerase β.

<p>Polθ-IN-7 (example 12) is an inhibitor of DNA polymerase θ (Polθ) with a Ki of 1.27 nM.</p>

Polθ-IN-8 (example 77) is a DNA polymerase θ (Polθ) inhibitor with an IC50 for Polθ ATPase activity of less than 100 nM. Polθ-IN-8 is useful for researching diseases related to Polθ activity, such as cancer.

Antiviralagent 67 (compound PC6) is an inhibitor of DENVNS5 (RNA-dependent RNA polymerase) with a Ki value of 1.12 nM.

RNase L ligand 3 is an RNase L ligand employed in the synthesis of F3-PEG8-RiboTAC.

6-N-Hydroxylaminopurine is a base analog with mutagenic activity.

Deoxythymidine-5'-triphosphate-d15 (dTTP-d15) dilithium is a deuterium-labeled form of deoxythymidine-5'-triphosphate. Deoxythymidine-5'-triphosphate (dTTP) is a triphosphate nucleotide utilized in DNA synthesis.