pan-4

Pan-KRAS-IN-4 (compound 5) is a potent KRAS inhibitor, demonstrating IC50 values of 0.37 nM for Kras G12C and 0.19 nM for Kras G12V [1].

Trk-IN-4 is an effective pan-Trk inhibitor in cell-based assays (IC50s: 1.9 nM, 2.6 nM, and 1.1 nM for TrkA, TrkB, and TrkC, respectively).

Dactolisib (BEZ235) is an orally bioavailable inhibitor of PI3K and mTOR (IC50s: 4 nM/5 nM/7 nM/75 nM, and 20.7 nM for p110α/p110γ/p110δ/p110β and mTOR).

Quisinostat (JNJ-26481585) (JNJ-26481585) is a novel second-generation HDAC inhibitor with highest potency for HDAC1 with IC50 of 0.11 nM, modest potent to HDACs 2, 4, 10, and 11; greater than 30-fold selectivity against HDACs 3, 5, 8, and 9 and lowest potency to HDACs 6 and 7.

FIIN-2, an irreversible, pan-FGFR inhibitor, inhibits FGFR1/2/3/4 with IC50 of 3.09 nM, 4.3 nM, 27 nM and 45.3 nM, respectively.

Destruxin B2 is a cyclic hexadepsipeptide mycotoxin that has been found in M. anisopliae and has antiviral, insecticidal, and phytotoxic activities.1,2,3 It inhibits secretion of hepatitis B virus surface antigen (HBsAg) by Hep3B cells expressing hepatitis B virus (HBV) DNA (IC50 = 1.3 μM).1 Destruxin B2 is toxic to Sf9 insect cells in an electric cell-substrate impedance sensing (ECIS) test with a 50% inhibitory concentration (ECIS50) value of 92 μM.4 It is also phytotoxic to B. napus leaves.3 |1. Yeh, S.F., Pan, W., Ong, G.-T., et al. Study of structure-activity correlation in destruxins, a class of cyclodepsipeptides possessing suppressive effect on the generation of hepatitis B virus surface antigen in human hepatoma cells. Biochem. Biophys. Res. Commun. 229(1), 65-72 (1996).|2. Male, K.B., Tzeng, Y.-M., Montes, J., et al. Probing inhibitory effects of destruxins from Metarhizium anisopliae using insect cell based impedance spectroscopy: Inhibition vs chemical structure. Analyst 134(7), 1447-1452 (2009).|3. Buchwaldt, L., and Green, H. Phytotoxicity of destruxin B and its possible role in the pathogenesis of Alternaria brassicae. Plant Pathol. 41(1), 55-63 (1992).

Vevorisertib (ARQ 751) is a highly effective oral compound that selectively inhibits pan-AKT serine/threonine kinases such as AKT1 (with an IC50 value of 0.55 nM), AKT2 (with an IC50 value of 0.81 nM), and AKT3 (with an IC50 value of 1.31 nM). This compound, either as a standalone treatment option or in combination with other anti-cancer agents, is ideally suited for conducting research on solid tumors characterized by PIK3CA/AKT/PTEN mutations[4].

h-NTPDase-IN-4 is a pan-inhibitor of NTPDase, which can inhibit h-NTPDase1, 1h-NTPDase2, h-NTPDase3, h-NTPDase8. The IC50 values were 3.58 μM, 10.21 μM, 0.13 μM and 13.57 μM, respectively.

LJI308 is a potent, and pan-RSK (p90 ribosomal S6 kinase) inhibitor with IC50 of 6 nM, 4 nM, and 13 nM for RSK1, RSK2, and RSK3, respectively.

PI3K/mTOR Inhibitor-4 is an orally active pan-I PI3K/mTOR inhibitor. PI3K/mTOR Inhibitor-4 is an enzyme inhibitor that acts on PI3Kα (IC50: 0.63 nM), PI3Kγ (IC50: 22 nM), PI3Kδ (IC50: 9.2 nM) and mTOR (IC50: 13.85 nM). PI3K/mTOR Inhibitor-4 can be used to study cancer.

PF-06273340 is an effective, Selective, and Peripherally Restricted Pan-Trk inhibitor (IC50: Trk-A = 6 nM; Trk-B = 4 nM; Trk-C = 3 nM). PF-06273340 has low metabolic turnover in HLM and hHep is a good substrate for efflux transporters P-gp (ER = 35.7) and BCRP (ER = 4.0) and has moderate passive permeability (RRCK Papp = 5.4 × 10 6 cm s 1).

NS5A-IN-4 (Compound 1.12) is a pan-genotypic, orally active inhibitor of the hepatitis C virus (HCV) NS5A, exhibiting IC50 values of 1.2, 2296, 4.6, 362, 10.3, and 693 pM against genotypes gT1b, gT1a, gT2a, gT3a, gT4a, and gT5a, respectively [1].

CGP74514A is a CDK1 inhibitor with potential anticancer activity. In U937 cells, CGP74514A - induced apoptosis (5 microM) became apparent within 4 hr and approached 100% by 24 hr. The pan- caspase inhibitor Boc-fmk and the caspase-8 inhibitor lETD-fmk opposed CGP74514A -induced caspase-9 activation and PARP degradation, but not cytochrome c or Smac/DIABLO release. CGP74514A -mediated apoptosis was substantially blocked by ectopic expression of full-length Bel- 2, a loop-deleted mutant Bcl-2, and Bcl-x(L). CGP74514A treatment (5 microM; 18 hr) resulted in increased p21(CIP1) expression, p27(KIP1) degradation, diminished E2F1 expression, and dephosphorylation of p34(CDC2). It also induced early (i.e., within 2 hr) inhibition of CDK1 activity and dephosphorylation of pRb, followed by pRb degradation, but did not block pRb phosphorylation at CDK2- and CDK4- specific sites. These findings indicate that the selective CDK1 inhibitor, CGP74514A , induces complex changes in cell cycle......

Gimeracil (Gimestat) is a competitive, reversible inhibitor of dihydropyrimidine dehydrogenase.

CEP-5214 is a potent, low-nanomolar pan inhibitor of human VEGF-R tyrosine kinases, displaying IC50 values of 16,8, and 4 nM for VEGF-R1/FLT-1, VEGF-R2/KDR, and VEGF-R3/FLT-4, respectively, with cellular activity equivalent to the isolated enzyme activity.

T025 is a pan CLK inhibitor with Kds of 4.8, 0.096, 6.5, 0.61, and 0.074 nM for CLK1-4, respectively. T025 displays anti-proliferative activities with IC50s of 30-300 nM in hematological and solid cancer cell lines. T025 can be used in studies about MYC-driven diseases.

AMG 511 is a potent and orally available pan inhibitor of class I PI3Ks(Kis of 4 nM, 6 nM, 2 nM and 1 nM for PI3Kα, β, δ and γ, respectively). It exhibits anti-tumor activity in mouse glioblastoma xenograft model[1]. AMG 511 significantly suppresses PI3K

MSA-2 dimer, a selective and orally active non-nucleotide STING agonist with a dissociation constant (Kd) of 145 μM, demonstrates prolonged antitumor and immunogenic activity. It non-covalently binds to STING as a dimer, showing greater permeability compared to cyclic dinucleotide[1].

CAY17c is an inhibitor of bromodomain-containing protein 4 (BRD4; IC50= 0.71 μM), as well as class I histone deacetylases (HDACs; IC50s = 0.046, 0.058, 0.075, and 0.167 μM for HDAC1, -2, -3, and -8, respectively) and class IIb HDACs (IC50s = 0.073 and 0.923 μM for HDAC6 and HDAC10, respectively).1It is selective for these enzymes over BRD2, -3, and -T (IC50s = >20 μM for all), as well as over HDAC4, -5, -7, -9, and -11 (IC50s = >10 μM for all). CAY17c inhibits the proliferation of HCT116, SW620, and DLD-1 colorectal cancer cells (IC50s = 0.45, 1.78, and 2.11 μM, respectively), as well as induces apoptosis and autophagy in HCT116 cells. It reduces tumor growth in an HCT116 mouse xenograft model when administered at doses of 15 and 30 mg/kg. 1.Pan, Z., Li, X., Wang, Y., et al.Discovery of thieno[2,3-d]pyrimidine-based hydroxamic acid derivatives as bromodomain-containing protein 4/histone deacetylase dual inhibitors induce autophagic cell death in colorectal carcinoma cellsJ. Med. Chem.63(7)3678-3700(2020)

LJH685 is an effective pan-RSK inhibitor for RSK1/2/3 (IC50: 6/5/4 nM).

Luxeptinib (CG-806) is a novel pan-FLT3/pan-BTK inhibitor that is administered orally. It exhibits potent and reversible inhibition of these enzymes, acting through a non-covalent mechanism. Luxeptinib effectively induces cell cycle arrest, apoptosis, or autophagy in acute myeloid leukemia cells [1][2][3][4].

Velpatasvir (GS-5816), also known as GS-5816, is a potent and selective Hepatitis C virus NS5A inhibitor. GS-5816 has demonstrated pan-genotypic activity and a high barrier to resistance in HCV replicon assays. GS-5816 demonstrated pangenotypic antiviral activity in patients with genotype 1-4 HCV infection. It will be further evaluated in combination with other pangenotypic direct-acting antivirals to achieve the goal of developing a well-tolerated, highly effective treatment for all HCV genotypes.

Quisinostat dihydrochloride (JNJ26854165(Quisinostat) 2HCl) is a novel second-generation HDAC inhibitor with highest potency for HDAC1 with IC50 of 0.11 nM in a cell-free assay, modest potent to HDACs 2, 4, 10, and 11; greater than 30-fold selectivity against HDACs 3, 5, 8, and 9 and lowest potency to HDACs 6 and 7. Phase 2.

AMG 900 is a potent and highly selective pan-Aurora kinases inhibitor for Aurora A B C with IC50 of 5 nM 4 nM 1 nM. It is >10-fold selective for Aurora kinases than p38α, Tyk2, JNK2, Met and Tie2. Phase 1.

Varlitinib (ASLAN001) is a potent, reversible, small molecule pan-EGFR inhibitor with IC50s of 7, 2, 4 nM for HER1, HER2 and HER4, respectively.

WNK463 is a pan-WNK-kinase inhibitor. It effectively inhibits the in vitro kinase activity of all four WNK family members (WNK1/2/3/4).