Cancer Targeted Therapy

JBJ-09-063 is a mutant-selective allosteric EGFR inhibitor with IC₅₀s of 0.147 nM, 0.063 nM, 0.083 nM and 0.396 nM for EGFR L858R, EGFR L858R/T790M, EGFR L858R/T790M/C797S and EGFRLT/L747S. JBJ-09-063 effectively reduces EGFR, Akt and ERK1/2 phosphorylation. JBJ-09-063 is effective across EGFR tyrosine kinase inhibitor (TKI)-sensitive and resistant models. JBJ-09-063 can be used for researching EGFR-mutant lung cancer.

(Z)-Leukadherin-1 (ADH-503 free base) is an orally active and allosteric CD11b agonist. (Z)-Leukadherin-1 leads to the repolarization of tumor-associated macrophages, reduction in the number of tumor-infiltrating immunosuppressive myeloid cells, and enhances dendritic cell responses.

DVD-445 (Compound 7) is a potent peptidomimetic covalent thioredoxin reductase 1 (TrxR1) inhibitor with an IC₅₀ of 0.60 μM for rat TrxR1. DVD-445 has good anticancer application.

BAY-474 is a tyrosine-protein kinase c-Met inhibitor. BAY-474 acts as an epigenetics probe.

Thalidomide-O-amido-PEG3-C2-NH2 hydrochloride is a synthesized E3 ligase ligand-linker conjugate that incorporates the Thalidomide based cereblon ligand and 3-unit PEG linker used in PROTAC technology.

Nampt-IN-5 is a potent nicotinamide phosphoribosyltransferase (NAMPT) inhibitor. Nampt-IN-5 also inhibits CYP3A4 activity and has cellular IC₅₀s of 0.7 nM and 3.9 nM against A2780 and COR-L23, respectively.

S2157, a N-alkylated tranylcypromine (TCP) derivative, is a potent lysine-specific demethylase 1 (LSD1) inhibitor. S2157 increases H3K9 methylation and reciprocal H3K27 deacetylation at super-enhancer regions. S2157 induces apoptosis in TCP-resistant T-cell acute lymphoblastic leukemia (T-ALL) cells by repressing transcription of the NOTCH3 and TAL1 genes. S2157 efficiently pass through the blood-brain barrier and can almost completely eradicate CNS leukemia in mice transplanted with T-ALL cells.

SNIPER(ER)-87 consists of an inhibitor of apoptosis protein (IAP) ligand LCL161 derivative that is conjugated to the estrogen receptor α (ERα) ligand 4-hydroxytamoxifen by a PEG linker, and efficiently degrades the ERα protein (IC₅₀=0.097 μM). SNIPER(ER)-87 preferentially recruits XIAP to ERα in the cells, and XIAP is the primary E3 ubiquitin ligase responsible for the SNIPER(ER)-87-induced ERα degradation.

Estradiol 3-sulfamate (BLE 00084; E2MATE; ES-J 995) is a potent, long-acting, and orally active steroid sulfatase inhibitor; inhibits estrone sulfatase with an IC₅₀ of 251 nM and a K_i of 133 nM.

Gozanertinib is an orally active furanopyrimidine-based EGFR inhibitor with IC₅₀s of 15 nM and 48 nM for EGFR^WT and EGFR^L858R/T790M, respectively. Gozanertinib can occupy the ATP-binding site. Gozanertinib has significant antitumor efficacy.

MS9427 is a potent PROTAC EGFR degrader with K_ds of 7.1 nM and 4.3 nM for EGFR WT and EGFR L858R, respectively. MS9427 selectively degrades the mutant but not the WT EGFR through both the ubiquitin/proteasome system (UPS) and autophagy/lysosome pathways. MS9427 potently inhibits the proliferation of NSCLC cells. MS9427 can be used for researching anticancer.

KRas G12C inhibitor 14 (Compound 17) is a potent KRAS G12C inhibitor (IC₅₀ = 18 nM).

OP-5244 is a potent and orally active inhibitor of CD73, with an IC₅₀ of 0.25 nM. OP-5244 reverses immunosuppression through blocking of adenosine production, and has the potential for the cancer research.

Fadrozole hydrochloride hemihydrate is an orally active, potent, selective and nonsteroidal aromatase inhibitor, with an IC₅₀ of 6.4 nM. Fadrozole hydrochloride hemihydrate inhibits the production of estrogen and progesterone, with IC₅₀ values of 0.03 and 120 μM. Fadrozole hydrochloride hemihydrate shows prevention of spontaneous tumours. Fadrozole hydrochloride hemihydrate can be used for the research of estrogen-dependent disease and cancer.

Thalidomide-Piperazine-PEG2-COOH is a synthesized E3 ligase ligand-linker conjugate that incorporates the Thalidomide based cereblon ligand and a linker used in PROTAC technology.

(S,R,S)-AHPC-C10-NH2 dihydrochloride (VH032-C10-NH2 dihydrochloride) is a synthesized E3 ligase ligand-linker conjugate that incorporates the (S,R,S)-AHPC based VHL ligand and a linker used for BET-Targeted PROTAC.

Vincristine-d₃ sulfate is the deuterium labeled Vincristine sulfate. Vincristine-1 sulfate (Leurocristine; NSC-67574; 22-Oxovincaleukoblastine) is a microtubule inhibitor that disrupts microtubule polymerization by binding to β-tubulin (with a K_i of 85 nM in bovine), arrests the cell cycle and induces apoptosis. Vincristine-1 sulfate inhibits cell replication, tumor blood flow and the proliferation of various cancer cells, while triggering effects such as oxidative stress, inflammation, calcium overload, epithelial-mesenchymal transition and peripheral neuropathic pain. Vincristine-1 sulfate upregulates the expression of various transporters and nuclear receptors, and enriches gastric cancer stem-like cells. Vincristine-1 sulfate is used in research related to various tumors including acute lymphoblastic leukemia, lymphoma, melanoma, gastric cancer, solid tumors and sarcomas.

PROTAC BRD9-binding moiety 1 is a compound that binds to BRD9, and used for inhibiting BRD9 activity, based on PROTAC.

Mocravimod (KRP-203 free base) is a sphingosine-1-phosphate receptor (S1PR) modulator that blocks the signal required by T cells to egress from lymph nodes and other lymphoid organs. Mocravimod preferentially binds to S1PR1 over S1PR2 and S1PR3 in cardiomyocytes. Mocravimod significantly lowered the concentration of reactive oxygen species (ROS), prevented mitochondrial permeability transition pore opening, boosted mitochondrial membrane potential (MMP), and increased phosphorylation of AKT, EKR, GSK-3β, JAK2, and STAT3. Mocravimod retains T cell effector function. Mocravimod can be used for the study of acute myelogenous leukemia, diabetes and Myocardial Ischemia-Reperfusion Injury (MIRI).

EML4-ALK kinase inhibitor 1 is a potent orally active inhibitor of echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK), with an IC₅₀ of 1 nM.