Ciclo celular / Checkpoint

<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>5'-ODMT cEt N-Bzm5 C Phosphoramidite is a strong modified nucleic acid analog for antisense oligos.</p>

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

<p>Lamifiban is a nonpeptide glycoprotein IIb/IIIa antagonist. It prevents platelet loss during experimental cardiopulmonary bypass.</p>

<p>Homouridine, an analogue of uridine, functions as an intermediate in the synthesis of MMP-2 inhibitor (compound I, IC50 = 150 μM).</p>

<p>Sovesudil (PHP-201) is a potent ROCK inhibitor with IC50 of 3.7 nM/2.3 nM for ROCK-I/II; lowers IOP without hyperemia.</p>

<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>

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

<p>CDK7-IN-25 (CY-16-1) is a potent CDK7 inhibitor with an IC50 value of less than 1nM, utilized in cancer research [1].</p>

<p>DNA gyrase B-IN-3 (Compound A), with an IC50 of less than 10 nM, acts as an inhibitor of bacterial DNA gyrase B and exhibits antibacterial activity against Gram</p>

<p>GSK2163632A is an insulin-like growth factor 1 receptor inhibitor that acts by binding to a novel region of the GRK active site cleft.</p>

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

<p>TC-A 2317 HCl inhibits Aurora A kinase (Ki 1.2 nM) over Aurora B (Ki 101 nM), displaying antitumor effects.</p>

<p>MC-Val-Cit-PAB-Ispinesib (Compound 509) is a potent Eg5 inhibitor and a click chemistry reagent [1].</p>

<p>GSK2850163 is a novel inhibitor of inositol-requiring enzyme-1 alpha (IRE1α) which can inhibit RNase activity and IRE1α kinase activity (IC50s: 200 and 20 nM).</p>

<p>CCT241533 hydrochloride is an effective and selective ATP competitive inhibitor of CHK2 (Ki: 1.16 nM; IC50: 3 nM).</p>

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

<p>CDK8-IN-3 is an inhibitor of CDK8.</p>

<p>USP1-IN-5 (compound 10) is a potent inhibitor of both USP1, with an IC50 of less than 50 nM, and MDA-MB-436 cells, where it also exhibits an IC50 of less than</p>

<p>Phototrexate, a photochromic Methotrexate analog, is a UVA-activated, reversible DHFR inhibitor with antifolate properties (IC50: 6 nM cis vs. 34 μM trans).</p>

<p>CI 972 anhydrous is an inhibitor of purine nucleoside phosphorylase (PNP) (Ki: 0.83 μM) used as a T cell-selective immunosuppressive agent.</p>

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

<p>PD-1/PD-L1-IN-33 (Compound N11), a PD-1/PD-L1 inhibitor, effectively impedes the interaction between PD-1 and PD-L1 with an IC50 of 6.3 nM.</p>

<p>'(S)-Cdc7-IN-18 from patent WO2020239107A1 inhibits CDC7, curbing MCM2 and tumor growth.'</p>

<p>LX7101 is a potent inhibitor of both LIM kinase (LIMK) 1 and 2, and Rho-associated kinase 1 (ROCK1) and ROCK2, with IC50 values of 32, 4.3, 69, and 32 nM, respectively. It is selective, demonstrated by its lack of cross-reactivity in a panel of binding assays involving 78 receptors, transporters, and an additional 430 kinases, at a concentration of 10 μM. The topical administration of LX7101 (3 μl of a 1 mg/ml solution) to the eye has been shown to reduce intraocular pressure in a dexamethasone-induced mouse model of glaucoma.</p>

<p>ICAM-1-IN-1 is a potent and selective E-selectin(IC50 = 7 nM) and ICAM-1(IC50 = 5 nM) inhibitor.</p>

<p>CDK7-IN-22 (compound 101) is a selective CDK7 inhibitor that exhibits antitumor activity, demonstrating specificity for CDK7 [1].</p>

<p>Tnp 351 is a novel antifolate drug being assessed for chemotherapy of lung cancer.</p>

<p>Halofuginone hydrochloride (RU-19110), a derivative of Febrifugine, functions as a competitive inhibitor of prolyl-tRNA synthetase, displaying a Ki value of 18.3 nM. This compound effectively inhibits type-I collagen synthesis, providing therapeutic benefits in osteoarthritis (OA) by impeding TGF-β signaling. Additionally, it serves as a potent pulmonary vasodilator, mainly through the activation of Kv channels and the inhibition of various calcium channels including voltage-gated, receptor-operated, and store-operated ones. Beyond its vascular effects, Halofuginone hydrochloride exhibits a broad spectrum of biological activities, including anti-malarial, anti-inflammatory, anti-cancer, and anti-fibrotic properties, supported by multiple studies.</p>

<p>SHP2/CDK4-IN-1: dual inhibitor, oral, potent (IC50: SHP2 4.3 nM, CDK4 18.2 nM), hinders TNBC growth, strong antitumor effects in mice.</p>

<p>KM05382 inhibits CDK9 and the transcription of GAPDH.</p>

<p>Fosfluridine tidoxil, a thymidylate synthase inhibitor, is used potentially for the treatment of colorectal cancer, and breast cancer.</p>

<p>CDK9-IN-9 is a potent and selective CDK9 inhibitor (IC50: 1.8 nM) with anti-cancer activity. It inhibits CDK2 (IC50: 155 nM).</p>

<p>XL413 hydrochloride (BMS-863233 Hydrochloride) is a potent, selective and ATP competitive inhibitor of Cdc7. XL413 hydrochloride also inhibits CK2 and PIM1.</p>

<p>Mefenidil (McN-2378), a selective cerebral vasodilator, was shown to increase CBF in healthy brains without stimulating O2 uptake in a dog anesthesia model.</p>

<p>CFI-402257 hydrochloride, a highly selective and orally bioavailable inhibitor targeting TTK/Mps1, demonstrates an in vitro IC50 value of 1.7 nM against TTK. This compound exhibits anti-cancer activity [1].</p>

<p>Cdc7-IN-7 is a potent inhibitor of Cdc7 kinase.</p>

<p>Leucettinib-92 (compound 92) is a kinase inhibitor selective for DYRK/CLK families, displaying IC50 values of 147 nM (CLK1), 39 nM (CLK2), 5.2 nM (CLK4), 0.8 μM</p>

<p>Palmitoyl 3-carbacyclic phosphatidic acid, a palmitoylated Carba-like cyclophosphatidic acid and LPA (lysophosphatidic acid) analog, possesses distinct biological activities compared to LPA, including the inhibition of RhoA activation and melanoma cell migration. This compound has demonstrated efficacy in inhibiting experimental lung metastasis and reducing tumor nodule counts in a B16-F0 xenograft mouse model [1].</p>

<p>Mevociclib (SY-1365) is a highly selective covalent inhibitor of CDK7. SY-1365 possesses therapeutic potential in both hematological and solid tumors.</p>

<p>Methotrexate-gamma-aspartate has growth inhibitory effects. It is used in antibody-targeted liposomes.</p>

<p>L-Methioninamide hydrochloride is a potent inhibitor of methionyl-tRNA synthetase that reduces the toxicity of CDDP.</p>

<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>AR-13503, a Netarsudil metabolite, is a ROCK inhibitor, potentially treating glaucoma and lowering eye pressure.</p>

<p>KSP-IA is a potent, specific, allosteric, and cell-active KSP inhibitor.</p>

<p>Lotrafiban: Oral GP IIb/IIIa inhibitor for treating coronary and cerebrovascular disease.</p>

<p>DCB-3503, a tylophorine analog, may fight cancer and aid immunosuppression by hindering protein synthesis and modulating HSC70 ATPase function.</p>

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

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

<p>Myt1-IN-3 is a potent inhibitor of Myt1 (IC50 &lt;10 nM) [1].</p>

<p>VER-00158411 is a checkpoint kinase 1 and CHK2 inhibitor (IC50: 4.4 nM and 4.5 nM, respectively).</p>

<p>Lotrafiban hydrochloride is an platelet glycoprotein IIb/IIIa blocker with oral activity.</p>

<p>L 738167 is a potent antagonist of the long-acting fibrinogen receptor.</p>

<p>SB-743921, a kinesin spindle protein (KSP) inhibitor, is used potentially for the treatment of non-Hodgkin's lymphoma (NHL).</p>

<p>Wee1 Inhibitor I is an ATP-binding site-targeting Wee1 inhibitor.</p>

<p>Antifolate C1 blocks purine creation, favors uptake via folate receptors/PCFT over RFC.</p>

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

<p>BIO-7662 is an effective and highly selective antagonist of α4β1 integrin.</p>

<p>5,11-methenyltetrahydrohomofolate blocks GAR &amp; AIR transformylase; used as an anti-purine drug.</p>

<p>5'-ODMT cEt N-Bz A Phosphoramidite Amidite, a locked nucleic acid (LNA) analogue, exhibits hybridization and mismatch discrimination capabilities similar to LNA, and shows resistance to exonuclease digestion [1].</p>

<p>Tacaciclib is a cyclin-dependent kinase (CDK) inhibitor with observed antineoplastic activity [1].</p>

<p>Diazoketone methotrexate is an analog of methotrexate with potential antitumor activity.</p>

<p>PLK1-IN-4: strong PLK1 blocker (&lt;0.508 nM IC50), inhibits cancer cell growth, triggers G2/M arrest and apoptosis.</p>

<p>TAK 029 is a local glycoprotein IIb/IIIa receptor inhibitor.</p>

<p>MU-380 is an effective and selective inhibitor of CHK1.</p>

<p>CDK7-IN-14, a potent CDK7 inhibitor from pyrimidines, may treat transcriptionally dysregulated cancers (CN114249712A).</p>

<p>FT206 is a carboxamide inhibitor of ubiquitin-specific protease[1].</p>

<p>N-desmethyl Netupitant is a metabolite of Netupitant and a potential Substance-P receptor agonist.</p>

<p>PLK1-IN-7 (compound 30e) is a potent inhibitor exhibiting an IC50 value of 0.66 nM and demonstrates significant antiproliferative and antitumor activities [1].</p>

<p>Pelitrexol (AG2037) is a GARFT inhibitor, which can inhibit the activity of mTORC1, block the cell cycle in the s-phase, with antiproliferative activity,NSCLC .</p>

<p>IIIM-290 is an oral CDK inhibitor (IC50s: 90 and 94 nM for CDK2/A and CDK9/T1).</p>

<p>CDK9-IN-19: Potent CDK9 inhibitor, anti-cancer, moderate pharmacokinetics, low hERG impact, effective in AML research.</p>

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

<p>Senexin C is a CDK8/19 inhibitor with anticancer activity.Senexin C inhibits the growth of MV4-11 leukemia cells.</p>

<p>BI-1950: potent inhibitor of LFA-1, key in immune function and drug target.</p>

<p>Teclistamab(JNJ-64007957) is a human bispecific monoclonal antibody targeting the CD3 receptor on t-cells and the BCMA for relapsed and refractory multiple myeloma.</p>

<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>

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

<p>PLK1/p38γ-IN-1 (compound 14) serves as a dual inhibitor targeting both PLK1 and p38γ kinases, effectively suppressing the proliferation of human hepatocellular</p>

<p>Carotegrast, an orally available α4 integrin receptor inhibitor, has anti-inflammatories activities.</p>

<p>LDC3140 is a potent inhibitor of Cyclin-dependent kinase 7 (CDK7).</p>

<p>GSK2646264 (Compound 44) inhibits SYK (pIC50=7.1) and kinases like LCK, LRRK2; penetrates skin.</p>

<p>PD-1/PD-L1-IN-27: potent anti-cancer, IC50 134nM, minimal T cell harm, boosts CD8+ T cells, reduces fatigue.</p>

<p>USP1-IN-3 is a selective inhibitor of USPI that inhibits USPI-UAFI (IC50&lt;30 nM). USP1-IN-3 can be used to study cancer.</p>

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

<p>DHODH-IN-14 is an analog of hydroxyfuran pyrimidine A771726.</p>

<p>CDK9-IN-2, a CDK9 inhibitor from patent WO/2012131594A1, IC50: 5 nM in A2058, 7 nM in H929 at 72hr.</p>

<p>Netropsin dihydrochloride, a small MGB, blocks topoisomerase I/II, hindering cleavable complex stabilization.</p>

<p>CCT251455, the mitotic kinase monopolar spindle 1 (MPS1/TTK) inhibitor, is a potent (IC50=3 nM) and specific chemical tool.</p>

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

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

<p>Solitomab (AMG 110) is a bispecific antibody targeting CD3 and EpCAM, used in uterine/ovarian carcinosarcoma research.</p>

<p>PD-1/PD-L1-IN-26 is a strong inhibitor with IC50 of 0.0380 μM that may boost immune response in cancer by aiding CD4+ T cell entry to tumors.</p>

<p>Senexin A hydrochloride functions as a selective inhibitor of CDK8/19, with an IC 50 of 280 nM for CDK8, and specifically inhibits p21-induced transcription without affecting other biological effects of p21. Additionally, it suppresses CMV-GFP induction and the stimulatory activity of the consensus NF-κB-dependent promoters [1] [2].</p>

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

<p>Spirofylline is an agent of bronchodilator, has the potential for asthma and bronchitis and emphysema treatment.</p>

<p>CDK4/6-IN-15: Oral, selective CDK4/6 inhibitor, halts cancer cell growth, G1 arrest, suppresses Rb phosphorylation.</p>

<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>OXA-06 hydrochloride, an ATP-competitive ROCK inhibitor, impedes anchorage-dependent growth and invasion in non-small cell lung cancer cell lines. It effectively inhibits cofilin phosphorylation without inducing apoptosis [1].</p>

<p>SC-52012 is a novel and potent fibrinogen receptor antagonist, an RGD mimetic, which inhibits platelet aggregation.</p>