isoforms

DFP00173 is a potent and selective aquaporin 3 (AQP3) inhibitor, with an IC50 of approximately 0.1-0.4 μM for both mouse and human AQP3. It demonstrates selectivity for AQP3 compared to homologous AQP subtypes AQP7 and AQP9.

MPI_5a is an effective and selective inhibitor of HDAC6 (IC50=36 nM). MPI_5a weakly inhibits other HDAC isoforms and it also inhibits acyl-tubulin accumulation in cells (IC50: 210 nM).

AZD8055 is an ATP-competitive mTOR inhibitor (IC50: 0.8 nM in MDA-MB-468 cells). It is ~1,000-fold selective for mTOR over all PI3K isoforms.

Zavondemstat (QC8222 free base) is a histone lysine demethylase 4 (KDM4) inhibitor with anticancer and antitumor activity for the study of triple-negative and breast cancers.

MSA-2 is an orally available non-nucleotide STING agonist. The non-covalent dimer of MSA-2 binds to STING with nanomolar affinity. It shows anti-tumor activity in syngeneic mouse tumor models, synergizes with anti-PD-1, stimulates tumor secretion of interferon-β, induces tumor regression, and has long-lasting anti-tumor immunity. [3]

Bevacizumab, a humanized monoclonal antibody, specifically and with high affinity binds to all isoforms of VEGF-A.

NOS-IN-1 (2-Imino-4-methylpiperidine acetate) is a potent and orally active inhibitor of NO synthase (NOS) isoforms. NOS-IN-1 exhibits IC50s of 0.1 μM, 0.2 μM, and 1.1μM for human iNOS (hiNOS), hnNOS and heNOS, respectively.

Zoniporide hydrochloride is a selective inhibitor of NHE-1 with IC50 of 14 nM which is >150-fold selectivity versus other NHE isoforms. Zoniporide hydrochloride shows an IC50 of 59 nM for NHE-1-dependent swelling of human platelets.

Izonsteride (LY320236) is a selective and potent 5alpha reductase inhibitor with dual action on the type I and type II isoforms of the enzyme.Izonsteride is used in the treatment of oncology and genitourinary disorders, and may be used in the study of prostate cancer.

5-(N,N-Hexamethylene)-amiloride (5-HMA) is an amiloride derivative that inhibits TRPA1-mediated calcium signaling (IC50: 35 μM). It functions as an inhibitor of the Na+ H+ exchanger (NHE) with Ki values ranging from 0.013 to 2.4 μM for various NHE isoforms. Additionally, 5-HMA blocks ASIC3 channels by 51% at 20 μM.

PI5P4Ks-IN-2 is an inhibitor of the phosphatidylinositol 5-phosphate 4-kinase PI5P4Kγ. Targeting the PI5P4K isoforms, PI5P4Ks-IN-2 inhibited PI5P4Kα, PI5P4Kβ, PI5P4Kγ, and PI5P4Kγ+, with IC50 values of <4.3, <4.6, 6.2, and 0.32, respectively.

JNK3 Inhibitor-4, a potent 2-aryl-1-pyrimidinyl-1H-imidazole-5-yl acetonitrile derivative, demonstrates a strong inhibitory effect on JNK3 with an IC 50 value of 1.0 nM. It exhibits exceptional selectivity against JNK3 when compared to other protein kinases, including isoforms JNK1 (IC 50 = 143.9 nM) and JNK2 (IC 50 = 298.2 nM). Additionally, JNK3 Inhibitor-4 benefits from neuroprotective properties and is predicted to permeate the blood-brain barrier effectively.

h-NTPDase-IN-2 is a broad-spectrum NTPDase inhibitor that inhibits multiple h-NTPDas isoforms.

JAK3-IN-11 (Compound 12) exhibits potent, noncytotoxic, irreversible, orally active JAK3 inhibitory activity (IC50 = 1.7 nM) with an excellent selectivity profile (>588-fold compared to other JAK isoforms), covalently binds to the ATP-binding pocket in JAK3. JAK3-IN-11 strongly inhibits JAK3-dependent signaling and T-cell proliferation which is a promising tool for studying autoimmune diseases [1].

Diclofenac (Diclofenacum) is a nonsteroidal benzeneacetic acid derivative with anti-inflammatory activity. Diclofenac binds and chelates both isoforms of cyclooxygenase (COX-1 and-2), thereby blocking the conversion of arachidonic acid to pro-inflammatory-proprostaglandins.

2-Naphthol is a metabolite of naphthalene, catalyzed by cytochrome P450 isoforms (CYP 1A1, CYP 1A2, CYP 2A1, CYP 2E1, and CYP 2F2). 2-Naphthol is cytotoxic.

Trometamol (Tromethamine) is a proton acceptor used to treat acidemia. It inhibits both isoforms of cyclooxygenases (COX1 and COX2), thereby blocking the conversion of arachidonic acid to pro-inflammatory pro-prostaglandins.

Fenofibrate (Lipanthyl) is a PPARα agonist (EC50=30 μM) and is selective. Fenofibrate also inhibits cytochrome P450 isoforms, such as CYP2C19, CYP2B6, CYP2C9, CYP2C8, and CYP3A4. Fenofibrate exhibits antihyperlipidemic activity.

Clomethiazole (Distraneurin) is an orally active GABAA agonist and it is an anticonvulsant agent. It also has the potential for treating convulsive status epilepticus. Chlormethiazole inhibits cytochrome P450 isoforms: CYP2A6 and CYP2E1 in human liver microsomes.

Dutasteride (GI 198745) is a 5-alpha-reductase inhibitor that inhibits both type-1 and type2 isoforms of the enzyme and is used to treat benign prostatic hyperplasia.

Cholesteryl sulfate sodium (Sodium Cholesteryl Sulfate) is a sterol sulfate in human plasma. Cholesteryl sulfate sodium is a component of cell membrane and has a regulatory function. Cholesteryl sulfate sodium also activates multiple protein kinase C (PKC) iso-enzymes, especially the ε, η and ζ isoforms.

Cedrol is a cedrane sesquiterpenoid and a tertiary alcohol,Cedrol inhibits the cytochrome P450 (CYP) isoforms CYP2B6 and CYP3A4 (Kis = 0.9 and 3.4 μM, respectively)

S-(2-aminoethyl) Isothiourea (dihydrobromide) is a non-selective inhibitor of all NOS isoforms. For human nNOS, eNOS, and iNOS, the Ki values are 1.8, 2.1, and 0.59 µM, respectively

SIRT5 inhibitor 4 (compound 11) is a dose-dependent and selective SIRT5 (Sirtuin5) inhibitor with an IC50 value of 26.4 μM for SIRT5 and no inhibitory effect on SIRT1/2/3 isoforms at 400 μM, with anticancer potential.