Cancer Targeted Therapy

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.

Cdc7-IN-5 (compound I-B) is a potent Cdc7 kinase inhibitor extracted from patent WO2019165473A1, compound I-B. Cdc7 is a serine-threonine protein kinase enzyme which is essential for the initiation of DNA replication in the cell cycle.

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.

KRAS G12C inhibitor 15 is a potent KRAS G12C inhibitor extracted from patent WO2019110751A1, compound 22, has an IC₅₀ of 5 nM.

(S)-Sunvozertinib ((S)-DZD9008), the S-enantiomer of Sunvozertinib, shows inhibitory activity against EGFR exon 20 NPH and ASV insertions, EGFR L858R/T790M mutation and Her2 exon20 YVMA insertion (IC₅₀=51.2 nM, 51.9 nM, 1 nM, and 21.2 nM, respectively). (S)-Sunvozertinib also inhibits BTK.

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).

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).

AZD3229 Tosylate is a potent pan-KIT mutant inhibitor for the treatment of gastrointestinal stromal tumors.

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

(S,R,S)-AHPC-PEG3-NH2 is a synthesized E3 ligase ligand-linker conjugate that incorporates the (S,R,S)-AHPC based VHL ligand and 3-unit PEG linker used in PROTAC technology.

IPN-60090 dihydrochloride is an orally active and highly selective inhibitor of glutaminase 1 (GLS1; IC₅₀=31 nM), with no activity observed against GLS-2. IPN-60090 dihydrochloride exhibits excellent physicochemical and pharmacokinetic properties in vivo. IPN-60090 dihydrochloride can be used for solid tumors research, such as lung and ovarian cancers.

ZM223 is a potent non-covalent NEDD8 activating enzyme (NAE) inhibitor, orally active.

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.

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.

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.

MS31 is a potent, highly affinity and selective fragment-like methyllysine reader protein spindlin 1 (SPIN1) inhibitor. MS31 potently inhibits the interactions between SPIN1 and H3K4me3 (IC₅₀=77 nM, AlphaLISA; 243 nM, FP). MS31 selectively binds Tudor domain II of SPIN1 (K_d=91 nM). MS31 potently inhibits binding of trimethyllysine-containing peptides to SPIN1. MS31 is not toxic to nontumorigenic cells.

JNJ-38877618 is a potent, highly selective, orally bioavailable Met kinase inhibitor with IC₅₀s of 2 and 3 nM for wild type and mutant Met, respectively.

Telatinib mesylate (Bay 57-9352 mesylate) is a potent and orally active VEGFR2, VEGFR3, PDGFα, and c-Kit inhibitor with IC₅₀s of 6 nM, 4 nM, 15 nM and 1 nM, respectively.

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.

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.