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].
GGTI-2133 is a direct and selective inhibitor of geran ylgeranyltransferase (GGTase). GGTI-2133 has the potential for eosinophilic airway inflammation such as asthma research[1].
EGFR-IN-60 (Compound 7d) shows obvious inhibition of EGFRWT, EGFRT790M, EGFRL858R and JAK3 with IC50s of 83, 26, 53, and 69 nM, respectively. EGFR-IN-60 potently inhibits the growth of H1975 cells harboring EGFRT790M mutation (IC50=1.32 µM) over A431 cells overexpressing EGFRWT (IC50=4.96 µM). EGFR-IN-60 exhibits good oral absorption, potent and safe antitumor activity. EGFR-IN-60 induces cell death through apoptosis supported by increased Bax/Bcl-2 ratio[1].
PD-089828 is an ATP competitive inhibitor of FGFR-1, PDGFR-β and EGFR (IC50s=0.15, 1.76, and 5.47 µM, respectively) and a noncompetitive inhibitor of c-Src tyrosine kinase (IC50=0.18 µM). PD 089828 also inhibits MAPK with an IC50 of 7.1 µM. PD-089828 inhibits PDGF-, EGF- and bFGF-mediated tyrosine kinase receptor autophosphorylation in vitro[1].
Zongertinib is a potent tyrosine kinase inhibitor. Zongertinib can be used as an antineoplastic agent. Zongertinib also has been tested as pHER2 and EGFR inhibitor inhibiting a wide variety of cancers[1][2].
HSP90-IN-13 (compound 5k) is a highly potent HSP90 pan inhibitor with an IC50 value of 25.07 nM. HSP90-IN-13 has multi-target activity against EGFR, VEGFR-2 and Topoisomerase-2. HSP90-IN-13 causes cell cycle arrest at G2/M phase and induces apoptosis of MCF-7 cells through mitochondrial-mediated pathway[1].
CMX-2043 is a novel analogue of α-Lipoic Acid (HY-N0492). CMX-2043 is effective in antioxidant effect, activation of insulin receptor kinase, soluble tyrosine kinase, and Akt phosphorylation. CMX-2043 shows protection against ischemia-reperfusion injury (IRI) in rat model[1][2].
c-met-IN-1 (compound 16) is a potent and selective c-Met inhibitor, with IC50 of 1.1 nM, with antitumor activity.[1].
Nilotinib D6 (AMN107 D6) is a deuterium labeled Nilotinib. Nilotinib is an orally available Bcr-Abl tyrosine kinase inhibitor with antineoplastic activity[1].
A-770041 is selective and orally active Src-family Lck inhibitor; A-770041 is a 147 nM inhibitor of Lck (1 mM ATP) and is 300-fold selective against Fyn, the other Src family kinase involved in T-cell signaling.IC50 value: 147 nMTarget: Lck
2-Bromo-6-methoxynaphthalene is an active intermediate in the production of anti-inflammatory agents like Naproxen and Nabumetone by Heck reaction. 2-Bromo-6-methoxynaphthalene has potential anti-inflammatory properties and Tyrosine-protein inhibitor properties. 2-Bromo-6-methoxynaphthalene can be used for the research of cancer[1].
Peonidin 3-O-glucoside chloride, an anthocyanin, act as an insulin secretagogue. Peonidin 3-O-glucoside chloride can increase glucose uptake in HepG2 cells. Peonidin 3-O-glucoside chloride has the potential for type-2 diabetes comorbidities research[1].
ARQ 069, an analog of ARQ 523, inhibits FGFR in an enantiospecific manner. ARQ 069 targets the unphosphorylated, inactive forms of FGFR1/FGFR2 kinases (IC50s of 0.84 μM and 1.23 μM, respectively). ARQ 069 inhibits FGFR1/FGFR2 autophosphorylation (IC50s of 2.8 and 1.9 μM, respectively) through a mechanism in a non-ATP competitive dependent manner[1].
Fazpilodemab (BFKB8488A) is a humanized, agonistic, bispecific antibody targeting fibroblast growth factor receptor 1c (FGFR1c) and Klothoβ. Fazpilodemab can be used for the research of type 2 diabetes mellitus (T2DM) or nonalcoholic fatty liver disease (NAFLD)[1].
Bixin (BX), isolated from the seeds of Bixa orellana, is a carotenoid, possessing anti-inflammatory, anti-tumor and anti-oxidant activities. Bixin treatment ameliorated cardiac dysfunction through inhibiting fibrosis, inflammation and reactive oxygen species (ROS) generation[1].
VEGFR-2-IN-25 (compound 5d) is a highly potent VEGFR-2 inhibitor with an IC50 value of 12.1 nM. VEGFR-2-IN-25 can be used for researching anticancer[1].
Irpagratinib (ABSK011) is an orally active inhibitor of fibroblast growth factor receptor (FGFR) tyrosine kinase, targeting to FGFR4 (IC50<10 nM). Irpagratinib inhibits the auto-phosphorylation of FGFR4 and blocks signal transduction from FGFR4 to downstream pathway activation. Irpagratinib exhibits high exposure in PK study in mouse, rat and dog, and also shows antineoplastic/anti-tumor activity in subcutaneous xenograft tumor models[1].
Poziotinib(NOV120101; HM781-36B) is an irreversible Pan-HER inhibitor with IC50s of 3/5/23 nM for HER1/HER2/HER4 respectively.IC50 value: 3/5/23 nM(HER1/HER2/HER4) [1]Target: pan-HER inhibitorin vitro: The IC50 levels of HM781-36B for N87 and SNU216 were 0.001 and 0.004 μmol/L, respectively, which was 10–1000 fold lower than the IC50 levels of other HER family TKIs. HM781-36B more potently inhibited the phosphorylation of HER family and downstream proteins, and induced apoptosis and G1 arrest compared to gefitinib or lapatinib [1]. HM781-36B is a potent inhibitor of EGFR in vitro, including the EGFR-acquired resistance mutation (T790M), as well as HER-2 and HER-4, compared with other EGFR tyrosine kinases inhibitors (erlotinib, lapatinib and BIBW2992). HM781-36B treatment of EGFR DelE746_A750-harboring erlotinib-sensitive HCC827 and EGFR L858R/T790M-harboring erlotinib-resistant NCI-H1975 NSCLC cells results in the inhibition of EGFR phosphorylation and the subsequent deactivation of downstream signaling proteins [2]. The addition of HM781-36B induced potent growth inhibition in both DiFi cells with EGFR overexpression and SNU-175 cells (IC50 = 0.003 and 0.005 μM, respectively). Furthermore, HM781-36B induced G1 arrest of the cell cycle and apoptosis, and reduced the levels of HER family and downstream signaling molecules, pERK and pAKT, as well as nonreceptor/cytoplasmic tyrosine kinase, BMX [3].in vivo: The growth of tumors in mice treated with HM781-36B alone or in combination with 5-FU was significantly inhibited compared with control mice, and tumor volume in mice receiving coadministraion of HM781-36B and 5-FU was smaller than tumor volume in mice receiving HM781-36B only [1].
Pacritinib is a potent inhibitor of both wild-type JAK2 (IC50=23 nM) and JAK2V617F mutant (IC50=19 nM). Pacritinib also inhibits FLT3 (IC50=22 nM) and its mutant FLT3D835Y (IC50=6 nM).
c-Met-IN-14 (compound 26af) is a selective inhibitor of c-Met kinase from N-sulfonylamidine-based derivatives, with an IC50 value of 2.89 nM. c-Met-IN-14 shows anticancer activity by blocking phosphorylation of c-Met, and arrests cell cycle at G2/M phase. c-Met-IN-14 induces apoptosis of A549 cells in a dose-dependent manner[1].
IRAK degrader-1 (example I-3) is a potent IRAK degrader[1].
Beta-hydroxyisovalerylshikonin is a natural product isolated from Lithospermium radix, acts as a potent inhibitor of protein tyrosine kinases (PTK), with IC50s of 0.7μM and 1μM for EGFR and v-Src receptor, respectively. Beta-hydroxyisovalerylshikonin is effective against a wide variety of tumor cell lines, and most efficiently induces cell-death in NCI-H522 and DMS114 cells[1].
LFM-A13 is a potent BTK, JAK2, PLK inhibitor, inhibits recombinant BTK, Plx1 and PLK3 with IC50s of 2.5 μM, 10 μM and 61 μM; LFM-A13 shows no effects on JAK1 and JAK3, Src family kinase HCK, EGFR and IRK.
BMS-536924 is an ATP-competitive IGF-1R/IR inhibitor with IC50 of 100 nM/73 nM.IC50 value: 100 nM (IGF-1R); 73 nM (IR) [1]Target: IGF-1R; IRin vitro: BMS-536924 also inhibits FAK and Lck with IC50 of 150 nM and 341 nM, respectively. BMS-536924 inhibits cellular proliferation and disrupts Akt and MAPK phosphorylation [1]. BMS-536924 inhibits IGF-I-stimulated IGF-1R signaling in MCF10A cells and blocks constitutive IGF-1R activity in CD8-IGF-1R-MCF10A. Preincubation of MCF10A cells with 1 μM BMS-536924 completely blocks the ability of IGF-I to stimulate IGF-1R phosphorylation. IGF-I stimulation results in increased phosphorylation of ERK1/2, GSK3β, and Akt. BMS-536924 inhibits this ligand-induced phosphorylation. Treatment of the CD8-IGF-1R-MCF10A cells with BMS-536924 results in a dose-dependent inhibition of phosphorylation with partial inhibition at 0.01 μM and 0.1 μM, but complete receptor inhibition at a concentration of 1 μM. Maximal inhibition of phosphorylated IGF-1R is observed as early as 10 minutes following incubation. BMS-536924 retains its ability to inhibit IGF-1R phosphorylation for up to 48 hours. Addition of BMS-536924 time-dependently inhibits Akt phosphorylation starting at 1 hour. By 48 hours, Akt activation is completely blocked [2]. in vivo: Oral administration of BMS-536924 at 100-300 mpk strongly inhibits IGR-1R Sal tumor model. Efficacy is also observed in the nonengineered Colo205 human colon carcinoma mode. Oral administration of 3 on a once a day schedule (100-300 mpk) or a twice a day schedule (50, 100 mpk) demonstrates antitumor activity in this tumor model. Oral glucose tolerance test (OGTT) shows 100 mpk (b.i.d.) causes a significant elevation in glucose levels after glucose challenge. The pharmacokinetic parameters of BMS-536924, administered orally in poly(ethylene glycol) 400 and water (80:20 v/v), are determined in mouse, rat, dog, and monkey. Good bioavailability is evident in all species. Significant nonlinear pharmacokinetics is observed in rodents at increasing p.o. dose [1]. Oral administration of 70 mg/kg BMS-536924 significantly inhibits tumor growth (TGBC-1TKB cells) inoculated in nude mice. BMS-536924 up regulates apoptosis in xenografts tumors. The treatment doesn't have adverse effects on the body weight of mice or the glucose levels at the time of death, suggesting tolerable toxicity [3].
HS-10296 is an orally available inhibitor of the epidermal growth factor receptor (EGFR) mutant form T790M, with potential antineoplastic activity.
Vosoritide (BMN 111) is a modified recombinant CNP (C-type natriuretic peptide) analogue, binds to NPR-B (natriuretic peptide receptor type B) and reduces the activity of FGFR3 (fibroblast growth factor receptor 3). Vosoritide can be used in achondroplasia and dwarfism research[1][2][3].
Ascrinvacumab (PF-03446962) is a human IgG2 monoclonal antibody targets ALK-1. Ascrinvacumab shows binding efficiency with human ALK1 with a Kd value of 7 nM. Ascrinvacumab can be used for the research of hepatocellular carcinoma (HCC)[1].
PROTAC IRAK4 degrader-4 is a PROTAC interleukin-1 receptor-associated kinase 4 (IRAK4) degrader extracted from patent US20190192668A1, compound I-127[1].
PTD10 is a highly potent PROTAC BTK degrader (DC50: 0.5 nM, KD: 2.28 nM). PTD10 degrades BTK in Ramos and JeKo-1 cells with DC50s of 0.5 and 0.6 nM respectively. PTD10 inhibits cell growth, and induces cell apoptosis via activation of the caspase-dependent pathway and mitochondrial pathway. PTD10 can be used for research of B-cell dysregulation[1].