Cancer Targeted Therapy

CFTR corrector 2 is a cystic fibrosis transmembrane conductance corrector (CFTR), extracted from patent US20140274933.

Necrostatin-34 (Nec-34), a RIPK1 kinase inhibitor, stabilizes RIPK1 kinase in an inactive conformation by occupying a distinct binding pocket in the kinase domain.

Spartalizumab is a humanized PD-1 IgG4 monoclonal antibody, with a K_d of 0.83 nM for human PD-1 and a K_d of 0.93 nM for cynomolgus monkey PD-1. Spartalizumab binds to PD-1 and blocks its interaction with the ligands PD-L1 and PD-L2. Spartalizumab induces increased IFNγ release. Spartalizumab can be used in the research of anaplastic thyroid carcinoma (ATC) and neuroendocrine neoplasms (NENs).

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

EGFR-IN-17 is a potent and selective inhibitor of the epidermal growth factor receptor ( IC₅₀ 0.0002 μM) to overcome C797S-mediated resistance.

HIF-2α-IN-2 is a hypoxia-inducible factors (HIF-2α) inhibitor extracted from patent WO2015035223A1, Compound 232, has an IC₅₀ of 16 nM in scintillation proximity assay (SPA).

MRTX9768 hydrochloride is a potent, selective, orally active, first-in-class PRMT5-MTA complex inhibitor.

Fasudil (HA-1077; AT877) dihydrochloride is a nonspecific RhoA/ROCK inhibitor and also has inhibitory effect on protein kinases, with an K_i of 0.33 μM for ROCK1, IC₅₀s of 0.158 μM and 4.58 μM, 12.30 μM, 1.650 μM for ROCK2 and PKA, PKC, PKG, respectively. Fasudil dihydrochloride is also a potent Ca²⁺ channel antagonist and vasodilator.

RAS GTPase inhibitor 1 (example 51) is a RAS GTPase inhibitor with anti-tumor activity, extracted from patent WO2018212774A1. RAS GTPase inhibitor 1 (example 51) exhibits an EC₅₀ less than 1 μM for at least one nucleotide exchange and an IC₅₀ less than 1 μM in H727 cells.

Cbl-b-IN-2 (Example 8) is an orally bioavailable compound, can inhibit the E3 enzyme Casitas B-lineage lymphoma proto-oncogene-b (Cbl-b) in the ubiquitin proteasome pathway. Cbl-b-IN-2 can be used to modulate the immune system and diseases amenable to immune system modulation. Cbl-b-IN-2 (Example 8) also may be administered to an individual with cancer, either alone or as part of a combination, with one or more of an immune checkpoint inhibitor, an anti-neoplastic agent, and radiation agent.

DB1976 is a selenophene analog of DB270 and a potent and cell-permeable fully efficacious transcription factor PU.1 inhibitor. DB1976 potently inhibits PU.1 binding (IC₅₀ of 10 nM) and strongly inhibits the PU.1/DNA complex (with high DB1976-λB affinity, K_D of 12 nM) in vitro. DB1976 has apoptosis-inducing effect.

(S,R,S)-AHPC-PEG2-NH2 dihydrochloride (VH032-PEG2-NH2 dihydrochloride) is a synthesized E3 ligase ligand-linker conjugate that incorporates the (S,R,S)-AHPC based VHL ligand and 2-unit PEG linker used in the synthesis of PROTACs.

Pomalidomide-PEG4-C2-NH2 is a synthesized E3 ligase ligand-linker conjugate that incorporates the Pomalidomide based cereblon ligand and 4-unit PEG linker used in PROTAC technology.

(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.

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.

Cimpuciclib tosylate is a selective CDK4 inhibitor (IC₅₀: 0.49 nM) that has anti-tumor activity.

AES-350 is a potent and orally active HDAC6 inhibitor with an IC₅₀ and a K_i of 0.0244 μM and 0.035 μM, respectively. AES-350 is also against HDAC3, HDAC8 in an enzymatic activity assay with IC₅₀ values of 0.187 μM and 0.245 μM, respectively. AES-350 triggers apoptosis in AML cells through HDAC inhibition and can be used for acute myeloid leukemia (AML) research.

IDH1 Inhibitor 1 is a potent, orally bioavailable, brain-penetrant and selective mutant IDH1 inhibitor with IC₅₀s of 0.021 μM, 0.045 μM, and 2.52 μM for IDH1^R132H, IDH1^R132C, and IDH1^WT, respectively. Anticancer activity.

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.

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.