Methylene blue (Basic Blue 9) hydrate is a guanylyl cyclase (sGC), monoamine oxidase A (MAO-A) and NO synthase (NOS) inhibitor. Methylene blue is a vasopressor and is often used as a dye in several medical procedures. Methylene blue hydrate through the nitric oxide syntase/guanylate cyclase signalling pathway to reduce prepulse inhibition. Methylene blue hydrate is a REDOX cycling compound and able to cross the blood-brain barrier. Methylene blue hydrate is a Tau aggregation inhibitor. Methylene blue hydrate reduces cerebral edema, attenuated microglial activation and reduced neuroinflammation[1][2][3].
A novel potent LIMK inhibitor with IC50 of 0.3 nM and 1 nM for LIMK1 and LIMK2, respectively; inhibits cofilin phosphorylation and increase αTubulin acetylation in cells; shows significant sensitivity against 656 cancer cell lines, and rhabdomyosarcoma, neuroblastoma and kidney cancer cells (mean EC50=19.2 uM).
5’(R)-C-Methyl-5-methyluridine is a thymidine analogue. Analogs of this series have insertional activity towards replicated DNA. They can be used to label cells and track DNA synthesis[1].
YK 4-279 is an inhibitor of RNA Helicase A (RHA) binding to the oncogenic transciption factor EWS-FLI1. YK-4-279 inhibits Ewing's sarcoma family tumor (ESFT) cell growth; YK-4-279 induces apoptosis. IC50 value:Target: RNA Helicase AES-FLI1 is an oncogenic fusion protein found in Ewing’s sarcoma, a family of undifferentiated tumors that occur throughout the body. The binding of RNA helicase A (RHA) to ES-FLI1 promotes its oncogenic function. YK-4-279 is an inhibitor of protein-protein interactions between ES-FLI1 and RHA. At 10 μM, YK-4-279 blocks RHA binding to ES-FLI1 and induces apoptosis of a panel of Ewing’s sarcoma tumor cell lines with IC50 values ranging from 0.5-2 μM. At 1.5 mg per dose, YK-4-279 reduces the growth of Ewing’s sarcoma orthotopic xenografts in mice after treatment with the inhibitor for two weeks.
GRP78-IN-3 is a selective Grp78 (HSPA5) inhibitor with an IC50 of 0.59 μM. GRP78-IN-3 is 7-fold selective for HspA5 compared to HspA9 (IC50 of 4.3 μM) and >20-fold selective for HspA5 compared to HspA2 (IC50 of 13.9 μM)[1].
8-Chloroinosine is a purine nucleoside analogue. Purine nucleoside analogs have broad antitumor activity targeting indolent lymphoid malignancies. Anticancer mechanisms in this process rely on inhibition of DNA synthesis, induction of apoptosis, etc[1].
Hsp90-IN-15 is an Hsp90 inhibitor with anticancer activity. Hsp90-IN-15 induces cell apoptosis, arrests the cell cycle at S phase and decreases the expression level of Hsp90 in Hela cell[1].
5-Furan-2-yl-2’-O-methyl uridine is a purine nucleoside analogue. Purine nucleoside analogs have broad antitumor activity targeting indolent lymphoid malignancies. Anticancer mechanisms in this process rely on inhibition of DNA synthesis, induction of apoptosis, etc[1].
AZ82 is a selective HSET/KIFC1 inhibitor, with a Ki of 43 nM and an IC50 of 300 nM for KIFC1.
Isopimpinellin, an orally active compound isolated from the roots of Pimpinella saxifrage. Isopimpinellin blocks DNA adduct formation and skin tumor initiation by 7,12-dimethylbenz[a]anthracene. Isopimpinellin possesses anti-leishmania effect[1].
ATM inhibitor-6 (A-193) is a selective ATM kinase inhibitor. ATM inhibitor-6 can be used in cancer research[1].
AT-533 is a potent Hsp90 and HSV inhibitor. AT-533 suppresses tumor growth and angiogenesis by blocking the HIF-1α/VEGF/VEGFR-2 signaling pathway. AT-533 also inhibits the activation of the downstream pathways, including Akt/mTOR/p70S6K, Erk1/2 and FAK. AT-533 inhibits the tube formation, cell migration, and invasion of human umbilical vein endothelial cells (HUVECs)[1][2][3].
ROCK-IN-4 is a potent ROCK inhibitor maintaining NO releasing ability. ROCK-IN-4 reversibly depolymerizes F-actin, and suppresses mitochondrial respiration in human trabecular meshwork (HTM) cells. ROCK-IN-4 can be used for glaucoma or ocular hypertension research[1].
CRA-026440 hydrochloride is a potent, broad-spectrum HDAC (HDAC) inhibitor. The Ki values against recombinant HDAC isoenzymes HDAC1, HDAC2, HDAC3, HDAC6, HDAC8, and HDAC10 are 4 nM, 14 nM, 11 nM, 15 nM, 7 nM, and 20 nM respectively. CRA-026440 hydrochloride shows antitumor and antiangiogenic activities[1].
2-Amino-6-chloro-9-(3-deoxy-3-fluoro-beta-D-ribofuranosyl)-9H-purine ((2R,3S,4S,5R)-2-(2-Amino-6-chloro-9H-purin-9-yl)-4-fluoro-5-(hydroxymethyl)tetrahydrofuran-3-ol) is a purine nucleoside analogue. Purine nucleoside analogs have broad antitumor activity targeting indolent lymphoid malignancies. Anticancer mechanisms in this process rely on inhibition of DNA synthesis, induction of apoptosis, etc[1].
Cdc7-IN-4 (compound I-C) is a potent Cdc7 kinase inhibitor extracted from patent WO2019165473A1, compound I-C. Cdc7 is a serine-threonine protein kinase enzyme which is essential for the initiation of DNA replication in the cell cycle[1].
Werner syndrome RecQ helicase-IN-3 is a potent and orally active werner syndrome recQ helicase (WRN) inhibitor with an IC50 value of 0.06 µM. Werner syndrome RecQ helicase-IN-3 shows antiproliferative activity. Werner syndrome RecQ helicase-IN-3 shows anticancer activity[1].
DBeQ is a selective, potent, reversible, and ATP-competitive p97 inhibitor, with an IC50 value of 1.5 μM and 1.6 μM for p97(wt) and p97(C522A), respectively; DBeQ also inhibits Vps4 with an IC50 of 11.5 μM.
Vorsetuzumab mafodotin (SGN-75) is an Auristatin-based anti-CD70 antibody-drug conjugate (ADC). Vorsetuzumab mafodotin consists of a humanized monoclonal antibody, Vorsetuzumab and an ADC cytotoxin MMAF. Vorsetuzumab mafodotin has antineoplastic activity[1].
Pixantrone (BBR 2778 (free base)) hydrochloride, a mitoxantrone analog, is a topoisomerase II inhibitor and DNA intercalator, with anti-tumor activity[1][2].
SR-3029 is a potent and ATP competitive CK1δ and CK1ε inhibitor, with IC50s of 44 nM and 260 nM, respectively, and Kis of 97 nM for both kinases.
Doxorubicin hydrochloride is a cytotoxic anthracycline antibiotic for the treatment of multiple cancers. The possible mechanisms by which doxorubicin acts in the cancer cell are intercalation into DNA and disruption of topoisomerase-II-mediated DNA repair.
Dasabuvir (ABT-333) sodium is a nonnucleoside hepatitis C virus (HCV) polymerase inhibitor. Dasabuvir sodium inhibits RNA-dependent RNA polymerase encoded by the HCV NS5B gene. Dasabuvir sodium inhibits genotype 1a (strain H77) and 1b (strain Con1) replicons, with EC50 values of 7.7 and 1.8 nM, respectively[1].
Cas9-IN-3 is a potent Cas9 inhibitor (IC50=28 μM). CRISPR/Cas systems have revolutionized gene editing in various species[1].
MTX115325 (Example 1) is an orally active, brain-penetrating USP30 inhibitor (IC50=12 nM) with neuroprotective activity. MTX115325 increases ubiquitination (EC50=32 nM) of the mitochondrial outer membrane protein TOM20 (a USP30 substrate), increasing mitophagy. MTX115325 prevents dopaminergic neuron loss and preserves striatal dopamine[1].
PPARγ/δ modulator 1 (compound 3e) is a potent PPAR modulator. PPARγ/δ modulator 1 is a PPARδ antagonist and a PPARγ partial agonist , with Ki values of 14.4 nM and 5.31 μM, respectively. PPARγ/δ modulator 1 has the EC50 of 7.3 and 12.6 μM for PPARδ corepression and adiponectin production, respectively[1].
Rho-Kinase-IN-2 (Compound 23) is an orally active, selective, and central nervous system (CNS)-penetrant Rho Kinase (ROCK) inhibitor (ROCK2 IC50=3 nM). Rho-Kinase-IN-2 can be used in Huntington’s research[1].
6(5H)-Phenanthridinone is a potent PARP-1 inhibitor and immunomodulator. 6(5H)-Phenanthridinone inhibits cell proliferation and can be used in cancer research[1].
2’-Deoxy-2’-fluoro-6-S-methyl-6-thio-arabino-inosine is a purine nucleoside analog. Purine nucleoside analogs have broad antitumor activity targeting indolent lymphoid malignancies. Anticancer mechanisms in this process rely on inhibition of DNA synthesis, induction of apoptosis, etc[1].
CT1113 is a potent USP28 and USP25 inhibitor. CT1113 decreases the MYC level in vivo，exhibits anti-tumor activity in mouse pancreatic cancer CDX model[1].