hcc827

EGFR-IN-1 hydrochloride is an irreversible and specific inhibitor of L858R T790M mutant EGFR, with 100-fold selectivity over wild-type EGFR. It exhibits potent antitumor and antiproliferative activity in H1975 cells and mutant HCC827 cells with IC50s of 4 and 28 nM, respectively.

Erlotinib (NSC-718781) is an EGFR inhibitor (IC50: 2 nM). It is used for the treatment of non-small cell lung cancer.

Ribociclib (LEE011) is an orally available, and highly specific CDK4 6 inhibitor (IC50:10 39 nM).

MS 39 is a highly effective, highly affinity and selective depressant of mutant epidermal growth factor receptor (EGFR) with high efficiency, high affinity and selectivity. MS 39, conjured by gefitinib to VHL ligand via a linker, effectively induced the degradation of mutant EGFR (DC50 values in HCC827(exon 19 del) and H3255 (L858R mutation) lung cancer cell lines were 5 nM and 3.3 nM, respectively). However, there was no significant effect in wild-type EGFR cell lines with concentrations up to 10 μM. MS 39 inhibited the proliferation of H3255 lung cancer cells in vitro and was bioavailable in mice after administration.

Telaglenastat (CB 839) (IC50 of 24 nM), an effective, specific, and oral inhibitor, which is bioavailable glutaminase, for recombinant human GAC.

EGFR-IN-1, an orally active and irreversible selective inhibitor targeting L858R T790M mutant EGFR, exhibits strong antiproliferative and antitumor activity, particularly against H1975 cells and first line mutant HCC827 cells. This compound potently inhibits Gefitinib-resistant EGFR L858R T790M mutations with a 100-fold selectivity over the wild-type EGFR.

Limertinib (ASK120067) is an orally active and highly efficient epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor targeting EGFR T790M. Limertinib can be used for studying non-small cell lung cancer.

Rezivertinib (BPI-7711) is an orally available, selective and potent inhibitor of tyrosine kinase (EGFR) with antitumor activity for central nervous system disorders.

8Br-HA is an inhibitor of fragile histidine triad diadenosine triphosphatase (FHIT; IC50= 0.12 μM).1It inhibits the growth of HCC827 and H460 lung cancer cells (GI50s = 0.87 and 5.9 μM, respectively). 1.Kawaguchi, M., Sekimoto, E., Ohta, Y., et al.Synthesis of fluorescent probes targeting tumor-suppressor protein FHIT and Identification of apoptosis-inducing FHIT inhibitorsJ. Med. Chem.64(13)9567-9576(2021)

Gefitinib-based PROTAC 3, which connects an EGFR binding element to a VHL ligand via a linker, induces EGFR degradation with DC50s of 11.7 nM and 22.3 nM in HCC827 (exon 19 del) and H3255 (L858R mutation) cells, respectively[1].

PD-L1-IN-1, a powerful PD-L1 inhibitor, demonstrated an IC50 of 115 nM. By forming a robust bond with the PD-L1 protein, PD-L1-IN-1 effectively suppressed tumor growth by enhancing the antitumor immune activity of peripheral blood mononuclear cells in co-cultures with PD-L1 expressing cancer cells (PC9 and HCC827 cells). It significantly elevated the release of interferon γ and induced apoptosis in cancer cells, while exhibiting minimal cytotoxicity in healthy cells [1].

WZ8040 is a novel mutant-selective irreversible EGFRT790M inhibitor, does not inhibit ERBB2 phosphorylation (T798I).

Olmutinib (HM61713, BI 1482694) is an orally available small molecule, a mutant-selective inhibitor of epidermal growth factor receptor (EGFR) with potential antineoplastic activity. Olmutinib binds to and inhibits mutant forms of EGFR, thereby leading to cell death of EGFR-expressing tumor cells. As this agent is selective towards mutant forms of EGFR, its toxicity profile may be reduced as compared to non-selective EGFR inhibitors which also inhibit the EGFR wild-type form.

PROTAC EGFR Degrader 3, a highly potent molecule, exhibits remarkable cellular activity against H1975 and HCC827 cells, maintaining high selectivity. It additionally reveals the lysosome's crucial role in the degradation mechanism of mutant EGFR [1].

PROTAC EGFR degrader 4 is a potent molecule designed to target and degrade mutant EGFR, effectively inducing degradation of EGFR del19 and EGFR L858R T790M with DC50 values of 0.51 nM and 126 nM, respectively. It significantly inhibits the growth of HCC827 and H1975 cell lines, demonstrating IC50 values of 0.83 nM and 203.1 nM, respectively. The induced degradation of EGFR by this compound is associated with autophagy [1].

PROTAC EGFR Degrader 5 (Compound 10), a potent degrader of EGFR Del19 in HCC827 cells, achieves this with a DC50 of 34.8 nM. This compound effectively induces apoptosis in HCC827 cells and causes cell cycle arrest in the G1 phase [1].

PROTAC EGFR degrader 6 is a potent PROTAC EGFR degrader that effectively reduces EGFR Del19 levels in HCC827 cells, exhibiting a DC50 of 45.2 nM. It notably promotes apoptosis and induces G1 phase arrest in HCC827 cells [1].

EGFR-IN-1 TFA is an orally active and irreversible L858R T790M mutant selective EGFR inhibitor. EGFR-IN-1 TFA potently inhibits Gefitinib-resistant EGFR L858R, T790M with 100-fold selectivity over wild-type EGFR . EGFR-IN-1 TFA displays strong antiproliferative activity against the H1975 cells and the first line mutant HCC827 cells. Antitumor activity [1] .

PROTAC EGFR degrader 8 (T-184) is a PROTAC that selectively degrades the epidermal growth factor receptor (EGFR) with a DC50 of 15.56 nM in HCC827 cells, and inhibits the growth of cell lines H1975, PC-9, and HCC827 with IC50 values of 7.72 nM, 121.9 nM, and 14.21 nM, respectively. This compound is used primarily for cancer research, particularly in the context of non-small cell lung cancer (NSCLC) [1].

Antiproliferative Agent-34 (Compound A14), a multitarget kinase inhibitor, demonstrates IC50 values of 177 nM for EGFR L858R T790M and 1567 nM for EGFR WT. Additionally, it inhibits JAK2, ROS1, FLT3, FLT4, and PDGFRα with respective IC50s of 30.93 nM, 106.90 nM, 108.00 nM, 226.60 nM, and 42.53 nM. In normoxic conditions, it suppresses the proliferation of H1975 and HCC827 cells with IC50 values below 40 nM, while under hypoxic conditions, its potency increases 4-6 fold, yielding IC50 values less than 10 nM [1].

Mobocertinib (tak788) is a potent inhibitor of epidermal growth factor receptor (EGFR) and an antineoplastic agent

VEGFR-IN-4 (Compound 6e), an inhibitor of the epidermal growth factor receptor (EGFR), demonstrates potent antiproliferative effects with an IC50 value of 24.6nM in HCC827 cells [1].

Antiproliferative agent-52 (Compound 4a) exhibits significant antiproliferative activity against four human tumor cell lines (A549, A2780, SKOV3, HCC827), with IC50 values ranging from 5.83 to 8.63 nM. This compound is useful for cancer research.

DFX117 is an orally effective selective inhibitor of PI3Kα and c-Met tyrosine kinase (c-Met). This compound inhibits the PI3K Akt mTOR pathway and suppresses the proliferation of NCI-H1975, NCI-H1993, and HCC827 cells, with IC50 values ranging from 0.02 to 0.08 µM. Additionally, DFX117 induces cell cycle arrest in the G0 G1 phase and triggers apoptosis (apoptosis) in A549 and NCI-H1975 cells. It also exhibits antitumor activity in mice.