AU-15330 is a proteolysis-targeting chimera (PROTAC) degrader of the SWI/SNF ATPase subunits, SMARCA2 and SMARCA4. AU-15330 induces potent inhibition of tumour growth in xenograft models of prostate cancer and synergizes with the AR antagonist enzalutamide. AU-15330 induces disease remission in castration-resistant prostate cancer (CRPC) models without toxicity[1].
7-Chloro-4-(piperazin-1-yl)quinolone is an important scaffold in medicinal chemistry. 7-Chloro-4-(piperazin-1-yl)quinolone is a potent sirtuin inhibitor and also inhibits the serotonin uptake (IC50 of 50 μM). 7-Chloro-4-(piperazin-1-yl)quinolone exhibits antimalarial activity on D10 and K1 strains of P. falciparum with IC50s of 1.18 μM and 0.97 μM, respectively[1].
Methylstat is a potent histone demethylases inhibitor. Methylstat shows anti-proliferative activity with low cytotoxicity. Methylstat induces apoptosis and cell cycle arrest at G0/G1 phase. Methylstat increases the expression of p53 and p21 protein levels. Methylstat inhibits angiogenesis induced by various cytokines. Methylstat can be used as a chemical probe for addressing its role in angiogenesis[1][2].
Alisertib (MLN 8237) sodium is an orally active and selective Aurora A kinase inhibitor (IC50=1.2 nM), which binds to Aurora A kinase resulting in mitotic spindle abnormalities, mitotic accumulation. Alisertib sodium induces apoptosis and autophagy through targeting the AKT/mTOR/AMPK/p38 pathway in leukemic cells. Antitumor activity[1][2][3].
SIRT6 activator 12q is potent, selective and orally active SIRT6 activator with IC50 values of 171.20, >200, >200, >200, 0.58 µM for SIRT1, SIRT2, SIRT3, SIRT5, SIRT6, respectively. SIRT6 activator 12q inhibits cell growth and migration. SIRT6 activator 12q induces Apoptosis and cell cycle arrest at G2 phase. SIRT6 activator 12q shows anticancer activity[1].
DCG066 is a G9a inhibitor in vitro.
LEM-14 is a specific inhibitor of histone lysine methyltransferase NSD2 (MMSET/WHSC1) with in vitro IC50 of 132 uM, and that is inactive against the closely related NSD1 and NSD3.
Remetinostat (SHP-141) is a hydroxamic acid-based inhibitor of histone deacetylase enzymes (HDAC) which is under development for the treatment of cutaneous T-cell lymphoma[1].
Curculigoside is the main saponin in C. orchioide, exerts significant antioxidant, anti-osteoporosis, antidepressant and neuroprotection effects. Curculigoside possesses significant anti-arthritic effects in vivo and in vitro via regulation of the JAK/STAT/NF-κB signaling pathway[1].
S 2101 is a lysine-specific demethylase 1 (LSD1) inhibitor with an IC50 of 0.99 μM, Ki of 0.61 μM and Kinact/Ki of 4560 M/s.
LSD1-UM-109 is a ighly potent and reversible LSD1 inhibitor with an IC50 of 3.1 nM. LSD1-UM-109 inhibits cell growth with IC50 values of 0.6 nM in the MV4;11 acute leukemia cell line and 1.1 nM in the H1417 small-cell lung cancer cell line[1].
CBP/p300-IN-19 is a potent p300/CBP HAT inhibitor with IC50s of 1.4, 2.2, >100, >100 µM for p300-HAT, CBP-HAT, PCAF, Myst3, respectively. CBP/p300-IN-19 shows antitumor activity[1].
Nimucitinib is a Janus kinase (JAK) inhibitor[1].
NSC 33994 (G6) is a selective JAK2 inhibitor, with an IC50 of 60 nM[1].
EPZ-719 is a novel and potent SETD2 inhibitor ( IC50 = 0.005 μM) with a high selectivity over other histone methyltransferases.
HDAC-IN-31 is a potent, selective and orally active HDAC inhibitor with IC50s of 84.90, 168.0, 442.7, >10000 nM for HDAC1, HDAC2, HDAC3, HDAC8, respectively. HDAC-IN-31 induces apoptosis and cell cycle arrests at G2/M phase. HDAC-IN-31 shows good antitumor efficacy. HDAC-IN-31 has the potential for the research of diffuse large B-cell lymphoma[1].
ZM 449829 is a potent, selective and ATP competitive inhibitor of JAK3, with a pIC50 of 6.8. ZM 449829 will be useful pharmacological tools for the investigation of the JAK3[1].
EPZ004777 is a potent, selective DOT1L inhibitor with an IC50 of 0.4 nM.
GSK2801 is a potent, selective and cell active acetyl-lysine competitive inhibitor of BAZ2A(Kd=136 nM) and BAZ2B(Kd=257 nM) bromodomains.IC50 value: 136 nM/257 nM(Kd, BAZ2A/BAZ2B) [1]Target: BAZ2A/2B inhibitorGSK2801 binds to BAZ2 bromodomains with dissociation constants (KD) of 136 and 257 nM for BAZ2B and BAZ2A, respectively. Crystal structures demonstrated a canonical acetyl-lysine competitive binding mode. Cellular activity was demonstrated using fluorescent recovery after photobleaching (FRAP) monitoring displacement of GFP-BAZ2A from acetylated chromatin. A pharmacokinetic study in mice showed that GSK2801 had reasonable in vivo exposure after oral dosing, with modest clearance and reasonable plasma stability. Thus, GSK2801 represents a versatile tool compound for cellular and in vivo studies to understand the role of BAZ2 bromodomains in chromatin biology.
PTG-0861 (JG-265) is a novel potent, selective HDAC6 inhibitor with IC50 of 5.92 nM, >36-fold selectivity over other HDACs.PTG-0861 (JG-265) displays HDAC6 cellular target engagement with EC50 of 0.59 uM (ELISA), has in vitro and cellular selectivity superior to HDAC6-selective inhibitor citarinostat (ACY-241).PTG-0861 (JG-265) demonstrates potency against several blood cancer cell lines (e.g. MV4-11, MM1S), whilst showing limited cytotoxicity against non-malignant cells and CD-1 mice.PTG-0861 (JG-265) exihibits promising in vitro pharmacokinetics achieved with good safety profile in cells and in vivo.
Valproic acid sodium salt is an anticonvulsants used to treat epilepsy, bipolar disorder and migraines. Valproic acid inhibits histone deacetylase 1 (HDAC1) with an IC50 of 0.4 mM.
JIB-04 is a pan-selective Jumonji histone demethylase inihibitor with IC50s of 230, 340, 855, 445, 435, 1100, and 290 nM for JARID1A, JMJD2E, JMJD3, JMJD2A, JMJD2B, JMJD2C, and JMJD2D, respectively.
CBP/p300-IN-19 hydrochloride is a potent and selective p300/CBP HAT inhibitor with IC50s of 1.4, 2.2, >100, >100 µM for p300-HAT, CBP-HAT, PCAF, Myst3, respectively. CBP/p300-IN-19 hydrochloride shows antitumor activity[1].
PROTAC BRD4 Degrader-1 is an efficacious BRD4 degrader with an IC50 of 41.8 nM against BRD4 BD1. PROTAC BRD4 Degrader-1 can effectively degrade BRD4 protein and suppress c-Myc expression[1].
Sirtuin modulator 2 (Compound 132) is a sirtuin modulator with an ED50 equal or less than 50 μM[1].
Benzenebutyric acid is an inhibitor of HDAC and endoplasmic reticulum (ER) stress, used in cancer and infection research.
Tenovin-1 is an inhibitor of sirtuin 1 and sirtuin 2, an activator of p53 and may have potential in the management of cancer.
BAZ2-ICR is a potent, selective, cell active and orally active BAZ2A/B bromodomains inhibitor with IC50s of 130 nM and 180 nM, and Kds of 109 nM and 170 nM, respectively. BAZ2-ICR shows 10-15-fold selectivity for binding BAZ2A/B over CECR2 and >100-fold selectivity over all other bromodomains. BAZ2-ICR is an epigenetic chemical probe[1].
Y06137 is a potent and selective BET inhibitor, which binds to the BRD4(1) bromodomain with a Kd of 81 nM[1]. Antitumor activity[1].
3-Deazaneplanocin A hydrochloride is a potent histone methyltransferase EZH2 inhibitor.