Picroside II, an iridoid compound extracted from Picrorhiza, exhibits anti-inflammatory and anti-apoptotic activities. picroside II alleviates the inflammatory response in sepsis and enhances immune function by inhibiting the activation of NLRP3 inflammasome and NF-κB pathways[1]. Picroside II is an antioxidant, exhibits a significant neuroprotective effect through reducing ROS production and protects the blood-brain barrier (BBB) after cerebral ischemia-reperfusion (CI/R) injury[2].
EGFR/ErbB-2/ErbB-4 inhibitor-3 (compound 29) is a potent tyrosine kinase inhibitor with IC50s of 0.3, 1.1, 0.5, 2.5, 24 nM for erbB1, erbB2, erbB4, EGF, HER, respectively[1].
SUN13837 is an orally active, potent and BBB-penetrated FGFR (fibroblast growth factor receptor) modulator. SUN13837 shows neuroprotective activity. SUN13837 can be used for neurodegenerative diseases research[1].
HA-100 hydrochloride is a potent protein kinase inhibitor, with IC50s of 4 μM, 8 μM, 12 μM and 240 μM for cGMP-dependent protein kinase (PKG), cAMP-dependent protein kinase (PKA), protein kinase C (PKC) and MLC-kinase, respectively. HA-100 hydrochloride also used as a ROCK inhibitor[1][2].
Sitravatinib is a novel small molecule inhibitor targeting multiple RTKs involved in driving sarcoma cell growth with IC50 of 3980 nmol/Lin vitro: MGCD516 is superior to other multi-kinase inhibitors in inhibiting cell proliferation, RTK phosphorylation, and phosphorylation of downstream effectors. MGCD516 is unique in a way that it has broad spectrum activity against many RTKs including c-Met, c-Kit, Axl, PDGFR, and Eph receptors that are known to play a role in driving sarcoma cell growthIn vivo: MGCD516 induces significant tumor growth suppression than imatinib and crizotinib.
Avapritinib is a potent and selective exon 17 mutant KIT kinase inhibitor with IC50 of 0.27 nM for KIT D816V.
ConB-1 is a potent and selective ALK inhibitor with low toxicity to normal cells[1].
UNC2881 is a potent and specific Mer kinase inhibitor; inhibits steady-state Mer kinase phosphorylation with an IC50 value of 22 nM. IC50 value: 22 nM [1]Target: Mer kinase inhibitorTreatment with UNC2281 is also sufficient to block EGF-mediated stimulation of a chimeric receptor containing the intracellular domain of Mer fused to the extracellular domain of EGFR. In addition, UNC2881 potently inhibits collagen-induced platelet aggregation, suggesting that this class of inhibitors may have utility for prevention and/or treatment of pathologic thrombosis.
AZ-23 is an ATP-competitive and orally bioavailable Trk kinase A/B/C inhibitor with IC50s of 2 nM (TrkA), 8 nM (TrkB), 24 nM (FGFR1), 52 nM (Flt3), 55 nM (Ret), 84 nM (MuSk), 99 nM (Lck), respectively.
GNF-7 inhibits Bcr-Abl WT and Bcr-Abl T315I with IC50 of 133 nM and 61 nM, respectively. IC50 value: 133 nM (Bcr-Abl WT), 61 nM (Bcr-Abl T315I)Target: Bcr-Ablin vitro: GNF-7 is amongst the first type II inhibitors capable of inhibiting T315I to be described and will serve as a valuable lead to design next generation Bcr-Abl kinase inhibitors. GNF-7 exhibits some selectivity (4 to 100-fold) for T315I Bcr-Abl (IC50 = 11 nM, in Ba/F3 cell line) relative to kinases such as TPR-Met, NPM-ALK, JAK-3, Flt-3. in vivo: GNF-7 displays significant efficacy against T315I-Bcr-Abl without appreciable toxicity in a bioluminescent xenograft mouse model using a transformed T315I-Bcr-Abl-Ba/F3 cell line that has a stable luciferase expression. GNF-7 exhibits excellent pharmacokinetic parameters in mice, with good systemic exposure (AUC = 26656 hrs*nM, Cmax = 3.6 uM) along with reasonable half life (t1/2=3.2 hrs) and favorable oral bioavailability (BAV=36%) being observed following oral administration of a single dose of 20 mg/kg.
c-Kit-IN-5 is potent inhibitor of c-Kit, with IC50s of 22 nM and 16 nM in kinase assay and cell assay, respectively. c-Kit-IN-5 shows more than 200-fold selectivity for c-Kit over KDR, p38, Lck, and Src. c-Kit-IN-5 also exhibits desirable pharmacokinetic properties[1].
Becotatug (JMT-101) is an IgG1 antibody targeting EGFR that can also be conjugated to Afatinib (HY-10261) and Osimertinib (HY-15772) as a synthetic ADC[1].
Olinvacimab (TTAC-0001) is a fully human anti-VEGFR2 monoclonal antibody. Olinvacimab inhibits VEGF binds to KDR with a Kd value of 0.23 nM. Olinvacimab has antiangiogenic activity. Olinvacimab can be used for the research of recurrent glioblastoma and breast cancer[1].
FGFR2-IN-3 is an orally active selective inhibitor of FGFR2[1].
Tunlametinib, an antineoplastic agent, is a tyrosine kinase inhibitor[1].
FGFR-IN-11 (compound I-5) is an orally active and covalent FGFR inhibitor with IC50 values of 9.9 nM (FGFR1), 3.1 nM (FGFR2), 16 nM (FGFR3), and 1.8 nM (FGFR4), respectively. FGFR-IN-11 inhibits multiple cancer cell proliferation with nanomolar activity. FGFR-IN-11 inhibits tumor growth significantly in xenograft mice models[1].
Bilobetin, an active component of Ginkgo biloba, can reduce blood lipids and improve the effects of insulin. Bilobetin ameliorated insulin resistance, increased the hepatic uptake and oxidation of lipids, reduced very-low-density lipoprotein triglyceride secretion and blood triglyceride levels, enhanced the expression and activity of enzymes involved in β-oxidation and attenuated the accumulation of triglycerides and their metabolites in tissues. Bilobetin also increased the phosphorylation, nuclear translocation and activity of PPARα accompanied by elevated cAMP level and PKA activity[1].
FGFR3-IN-4 is a selective FGFR3 inhibitor, with an IC50 value of less than 50 nM. FGFR3-IN-4 is at least 10 fold more selective for FGFR3 than for FGFR1[1].
BTK inhibitor 8 (Compound 27) is a Btk inhibitor with an IC50 of 0.11 nM. BTK inhibitor 8 inhibits B cell activation in hWB with an IC50 of 2 nM[1].
Sozinibercept (OPT 302; VGX-300) is a soluble form of VEGFR-3, potently inhibits the activity of VEGF-C/D, which are the proangiogenic factors, inhibiting angiogenesis and vascular leakage. Sozinibercept also inhibits diabetic retinal edema in rats[1][2][3].
Rhoifolin is a flavone glycoside isolated from Citrus grandis (L.) Osbeck leaves. Rhoifolin is beneficial for diabetic complications through enhanced adiponectin secretion, tyrosine phosphorylation of insulin receptor-β and glucose transporter 4 (GLUT 4) translocation[1]. Rhoifolin ameliorates titanium particle-stimulated osteolysis and attenuates osteoclastogenesis via RANKL-induced NF-κB and MAPK pathways[2].
Erlotinib D6 (CP-358774 D6) is a deuterium labeled Erlotinib (CP-358774). Erlotinib is a directly acting inhibitor EGFR tyrosine kinase inhibitor with an IC50 of 2 nM for human EGFR[1].
Adaphostin (NSC 680410), the adamantyl ester of AG957, is a potent p210bcr/abl inhibitor (IC50=14 μM). Adaphostin induces apoptosis in T-lymphoblastic human leukemia cell lines (IC50 ranging from 17 to 216 nM). Adaphostin has significant and selective activity against chronic and acute myeloid leukemia cells. Adaphostin increased the level of reactive oxygen species (ROS) within CLL B cells[1][2][3].
BTK ligand 1 (compound 1) is a ligand targeting Bruton’s tyrosine kinase (Btk). BTK ligand 1 can combine with E3 ligase ligand (Ligand for E3 Ligase) through PROTAC Linker to form PROTAC. PROTACs targeting Btk can be used in the study of chronic lymphocytic leukemia (CLL) and other BK cell malignancies[1].
SB1317 is a potent inhibitor of CDK2, JAK2, and FLT3 for the treatment of cancer, with IC50 of 13, 73, and 56 nM for CDK2, JAK2 and FLT3, respectively.
EGFR-IN-27 is a potent EGFR inhibitor with IC50s of <50 nM for EGFR Del, L858R, Del/T790M, L858R/T790M, Del/T790M/C797S, and L858R/T790M/C797S, respectively (WO2021249324A1, compound 511)[1].
Defactinib is a novel FAK inhibitor with potential antiangiogenic and antineoplastic activities.
Lanraplenib succinate (GS-9876 succinate) is a highly selective and orally active SYK inhibitor (IC50=9.5 nM) in development for the treatment of inflammatory diseases. Lanraplenib succinate (GS-9876 succinate) inhibits SYK activity in platelets via the glycoprotein VI (GPVI) receptor without prolonging bleeding time (BT) in monkeys or humans[1][2][3].
Norleual is an angiotensin IV analog. Norleual is a highly potent HGF/c-MET inhibitor (IC50=3 pM). Norleual inhibits HGF-induced MDCK cell proliferation and invasion in vitro. Norleual also is an AT4 receptor antagonist; disrupts LTP stabilization. Antiangiogenic.
IRAK4-IN-4 is an interleukin-1 receptor–associated kinase 4 (IRAK4) inhibitor extracted from patent CN107163044A, Compound15, has an IC50 of 2.8 nM. IRAK4-IN-4 also inhibits cyclic GMP-AMP synthase (cGAS) with an IC50 of 2.1 nM[1].