PF-543 hydrochloride (Sphingosine Kinase 1 Inhibitor II hydrochloride) is a potent, selective, reversible and sphingosine-competitive SPHK1 inhibitor with an IC50 of 2 nM and a Ki of 3.6 nM. PF-543 hydrochloride is >100-fold selectivity for SPHK1 over SPHK2. PF-543 hydrochloride is an effective potent inhibitor of sphingosine 1-phosphate (S1P) formation in whole blood with an IC50 of 26.7 nM. PF-543 hydrochloride induces apoptosis, necrosis, and autophagy[1][2][3].
Mulberroside A, the major active anti-tyrosinase compound in the root bark extract of Morus alba L. (Moraceae), is widely employed as an active ingredient in whitening cosmetics. IC50 value: 1.29 μmol/L (inhibition of the monophenolase activity); KI value: 0.385 μmol/L (the inhibition constant of the effectors on tyrosinase); KIS value: 0.177 μmol/L (the inhibition constant of the enzyme-substrate complex) [3] Target:In vitro: Mulberroside A decreased the expressions of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6 and inhibited the activation of NALP3, caspase-1, and nuclear factor-κB and the phosphorylation of extracellular signal-regulated protein kinases, the c-Jun N-terminal kinase, and p38 exhibiting anti-inflammatory antiapoptotic effects [1]. Mulberroside A treatment significantly decreased the mRNA and protein expression of P-gp in Caco-2 cells after treatment with Mulberroside A (5–20 μM). PKC and NF-κB might play crucial roles in Mulberroside A-induced suppression of P-gp [2]. In vivo:
S65487 (VOB560) sulfate is a potent and selective Bcl-2 inhibitor. S65487 sulfate is also active on BCL-2 mutations, such as G101V and D103Y. S65487 sulfate has poor affinity with MCL-1, BFL-1 and BCL-XL. S65487 sulfate induces apoptosis and has anticaner activities[1][2].
EGFR-IN-57 (Compound 25a) is a potent, orally active EGFR-TK inhibitor with an IC50 of 0.054 µM. EGFR-IN-57 also inhibits VEGFR-2, CK2α, topoisomerase IIβ and tubulin polymerization with IC50 values of 0.087, 0.171, 0.13 and 3.61 µM, respectively. EGFR-IN-57 induces cell cycle arrest at G2/M and pre-G1 phases. EGFR-IN-57 induces cancer cell apoptosis[1].
STM3006 is a highly potent, selective and orally active METTL3 inhibitor. STM3006 can be used for the research of acute myeloid leukaemia (AML)[1].
Delta-12-Prostaglandin J2 (Δ12-PGJ2) is a cyclopentenone prostaglandin (PG) with anti-proliferative effect on various tumor cell growth. Delta-12-Prostaglandin J2, a naturally occurring dehydration product of prostaglandin D2, is able to induce apoptosis in HeLa cells via caspase activation[1][2].
DCVC inhibits pathogen-stimulated TNF-α in human extra placental membranes in vitro.Target: TNF-αin vitro: DCVC inhibits pathogen stimulated cytokine release from tissue punch cultures. DCVC (5-50 μM) significantly inhibits LTA-, LPS-, and GBS-stimulated cytokine release from tissue cultures as early as 4 h (P ≤ 0.05). In contrast, TCA (up to 500 μM) does not inhibit LTA-stimulated cytokine release from tissue punches. DCVC effects on LTA-stimulated and LPS-stimulated TNF-α release from tissue punch cultures of extraplacental membranes. DCVC effects on GBS-stimulated release of pro-inflammatory cytokines from extraplacental membranes in transwell cultures.
Vandetanib-d4 (ZD6474-d4) is the deuterium labeled Vandetanib. Vandetanib (ZD6474) is a potent, orally active inhibitor of VEGFR2/KDR tyrosine kinase activity (IC50=40 nM). Vandetanib also has activity versus the tyrosine kinase activity of VEGFR3/FLT4 (IC50=110 nM) and EGFR/HER1 (IC50=500 nM)[1][2].
RDR03871 (compound 2) is a potent dual MDM2/MDM4 inhibitor with IC50 values of 35.4 nM and 10.4 nM for MDM2-p53 and MDM4-p53, respectively[1].
[8]-Shogaol, one of the pungent phenolic compounds in ginger, exhibits anti-platelet activity (IC50=5 μM) and inhibits COX-2 (IC50=17.5 μM). [8]-Shogaol induces apoptosis in human leukemia cells[1][2][3][4].
BV6 is an antagonist of cIAP1 and XIAP, members of the inhibitors of apoptosis (IAP) family.
Methotrexate (Amethopterin) disodium, an antimetabolite and antifolate agent, inhibits the enzyme dihydrofolate reductase, thereby preventing the conversion of folic acid into tetrahydrofolate, and inhibiting DNA synthesis. Methotrexate disodium, also an immunosuppressant and antineoplastic agent, is used for the research of rheumatoid arthritis and a number of different cancers (such as acute lymphoblastic leukemia)[1][2][3].
D-Mannitol-13C6 is the 13C labeled D-Mannitol[1]. D-Mannitol is an osmotic diuretic agent and a weak renal vasodilator[2][3][4].
Amiloride (hydrochloride) is an epithelial sodium channel (ENaC) inhibitor and a competitive inhibitor of Urokinase-type plasminogen activator (uPA).
PRIMA-1MET restores wild-type conformation and function to mutant p53, and triggers apoptosis in tumor cells. PRIMA-1MET also targets the selenoprotein thioredoxin reductase 1 (TrxR1), a key regulator of cellular redox balance.
9-Methoxycamptothecin (MCPT), isolated from Nothapodytes foetida, has antitumor activities through topoisomerase inhibition. 9-Methoxycamptothecin (MCPT) induces strong G2/M arrest and apoptosis in cancer[1][2].
Apoptin-derived peptide is an antitumor polypeptide with cytotoxicity. Apoptin-derived peptide promotes apoptosis and necrosis of gastric cancer (GC) cells by regulating PI3K/AKT/ARNT signaling. Apoptin-derived peptide inhibited the invasion and migration of cancer cells, and inhibited the expression and phosphorylation of the subunit p85 of PI3K, which further inhibited the PI3K/AKT pathway involved in the development of gastric cancer[1].
Gemcitabine monophosphate (Gemcitabine 5′-phosphate) disodium can be used to synthesis nanoparticles. Gemcitabine monophosphate disodium is one of the active intermediates of Gemcitabine (HY-17026). Gemcitabine monophosphate disodium can be used for bladder cancer research[1].
Fludarabine triphosphate (F-ara-ATP), the cytotoxic metabolite of Fludarabine phosphate (HY-B0028), inhibits ribonucleotide reductase and DNA polymerase and ultimately leads to cellular apoptosis[1].
Phenoxodiol, a synthetic analog of Genestein, activates the mitochondrial caspase system, inhibits XIAP (an apoptosis inhibitor), and sensitizes the cancer cells to Fas-mediated apoptosis. This agent also inhibits DNA topoisomerase II by stabilizing the cleavable complex. Phenoxodiol induces cell cycle arrest in the G1/S phase of the cell cycle and upregulates p21WAF1 via a p53 independent manner[1][2].
Mitomycin C is an antitumor drug and antibiotic that shows extraordinary ability to inhibit DNA synthesis.
GKK1032B is an alkaloid compound that can be found in endophytic fungus Penicillium sp. GKK1032B can induce the apoptosis of human osteosarcoma MG63 cells through caspase pathway activation[1].
Lithium chloride hydrate, an orally active mood stabilizer, is a potent virus inhibitor and effective immunomodulatory agent. Lithium chloride hydrate has antidepressant activity by inhibiting GSK3β and promoting neurogenesis. Lithium chloride hydrate alleviates cognition dysfunction and the symptoms of acute mania and depression. Lithium chloride hydrate can also be used for research of virus infection and Alzheimer's disease[1][2][3].
Siomycin A is a thiopeptide antibiotic and is a Forkhead box M1(FOXM1) selective inhibitor without affecting other members of the Forkhead box family. Siomycin A has anti-tumor and promotes apoptosis[1][2].
Apratoxin A, a cyanobacterial metabolite, mediates antiproliferative activity through the induction of G1 cell cycle arrest and an apoptotic cascade. Apratoxin A associates with Hsp70/Hsc70 to promote the degradation of Hsp90 client proteins. Apratoxin A can specifically bind the Sec61 complex[1][2][3].
RIPK3-IN-1 is a RIPK3 type II DFG-out inhibitor with an IC50 of 9.1 nM. RIPK3-IN-1 inhibits RIPK1 and RIPK2 with IC50s of 5.5 and >10 μM. RIPK3-IN-1 is also a c-Met kinase inhibitor with an IC50 of 1.1 μM[1].
Famitinib (SHR1020), an orally active multi-targeted kinase inhibitor, inhibits the activity of c-kit, VEGFR-2 and PDGFRβ with IC50 values of 2.3 nM, 4.7 nM and 6.6 nM, respectively[1]. Famitinib exerts powerful antitumor activity in human gastric cancer cells and xenografts.Famitinib triggers apoptosis[2].
Verrucarin A (Muconomycin A), a Type D macrocyclic mycotoxin derived from the pathogen fungus Myrothecium verrucaria, is an inhibitor of protein synthesis. Verrucarin A inhibits growth of leukemia cell lines and activates caspases and apoptosis and inflammatory signaling in macrophages. VA effectively increased the phosphorylation of p38 MAPK and diminished the phosphorylation of ERK/Akt. VA caused cell cycle deregulation through the induction of p21 and p53[1][2].
MMP2-IN-1 is a moderate potenet MMP2 inhibitor with IC50 of 6.8 µM. MMP2-IN-1 exhibits remarkable antiproliferative activity in certain cancer cells by arresting the cell cycle and inducing apoptosis[1].
RIPK2 inhibitor OD36 is a potent, specific, ATP-competitive inhibitor of RIPK2 with IC50 of 5.3 nM, inhibits Tyr and Ser/Thr-directed activities of RIPK2; inhibits both RIPK2 tyrosine autophosphorylation as well as downstream NF-κB and MAPK signaling induced by MDP, downregulates a panel of RIPK2 kinase-dependent genes; reduces cellular infiltration in an in vivo MDP-induced peritonitis model; also shows high affinity for cyclin G-associated kinase (GAK) with Ki of 3.8 nM.