HER2/ErbB2 选择性抑制剂

Tucatinib

Tucatinib (Irbinitinib, ONT-380, ARRY-380) is an oral, potent, selective, reversible and ATP-competitive small-molecule inhibitor of ErbB-2 (also called HER2) with IC50s of 8 nM and 7 nM for ErbB-2 and p95 HER2, respectively in cell-based assays, showing ~500-fold selective for HER2 vs EGFR. It has potential antineoplastic activity.

CP-724714

CP-724714 is a potent, selective inhibitor of HER2/ErbB2 with IC50 of 10 nM, >640-fold selectivity against EGFR, InsR, IRG-1R, PDGFR, VEGFR2, Abl, Src, c-Met etc in cell-free assays. Phase 2.

HER2-Inhibitor-1

HER2-Inhibitor-1 is an analog of ARRY-380. ARRY-380 is a potent and selective HER2 inhibitor with IC50 of 8 nM, equipotent against truncated p95-HER2, 500-fold more selective for HER2 versus EGFR.

BDTX-189

BDTX-189 is a potent and selective inhibitor of allosteric EGFR and HER2 oncogenic mutations with Kd of 0.2 nM, 0.76 nM, 13 nM and 1.2 nM for EGFR, HER2, BLK and RIPK2, reapectively. BDTX-189 exhibits anticancer activity.

Varlitinib

Varlitinib (ARRY334543) is a selective and potent ErbB1(EGFR) and ErbB2(HER2) inhibitor with IC50 of 7 nM and 2 nM, respectively. Phase 2.

Sapitinib (AZD8931)

Sapitinib (AZD8931) is a reversible, ATP competitive inhibitor of EGFR, ErbB2 and ErbB3 with IC50 of 4 nM, 3 nM and 4 nM in cell-free assays, more potent than Gefitinib or Lapatinib against NSCLC cell, 100-fold more selective for the ErbB family than MNK1 and Flt. Phase 2.

Allitinib tosylate

Allitinib tosylate (AST-1306 TsOH, AST-6) is a novel irreversible inhibitor of EGFR and ErbB2 with IC50 of 0.5 nM and 3 nM, also effective in mutation EGFR T790M/L858R, more potent to ErbB2-overexpressing cells, 3000-fold selective for ErbB family than other kinases.

Poziotinib

Poziotinib is an irreversible pan-HER inhibitor with IC50 of 3.2 nM, 5.3 nM and 23.5 nM for HER1, HER2, and HER4, respectively. Poziotinib also induces apoptosis and G1 cell cycle arrest. Phase 2.

AEE788 (NVP-AEE788)

AEE788 (NVP-AEE788) is a potent inhibitor of EGFR and HER2/ErbB2 with IC50 of 2 nM and 6 nM, less potent to VEGFR2/KDR, c-Abl, c-Src, and Flt-1, does not inhibit Ins-R, IGF-1R, PKCα and CDK1. Phase 1/2.

Epertinib hydrochloride

Epertinib hydrochloride (S-222611 hydrochloride) is a potent, orally active, reversible, and selective tyrosine kinase inhibitor of EGFR, HER2 and HER4 with IC50 of 1.48 nM, 7.15 nM and 2.49 nM, respectively. Epertinib hydrochloride (S-222611 hydrochloride) exhibits antitumor activity.

Canertinib dihydrochloride

Canertinib (CI-1033, PD-183805, compound 18) dihydrochloride is a potent and irreversible inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase. Canertinib dihydrochloride inhibits cellular EGFR and ErbB2 autophosphorylation with IC50 of 7.4 nM and 9 nM, respectively.

Canertinib (CI-1033)

Canertinib (CI-1033, PD183805) is a pan-ErbB inhibitor for EGFR and ErbB2 with IC50 of 1.5 nM and 9.0 nM, no activity to PDGFR, FGFR, InsR, PKC, or CDK1/2/4. Phase 3.

Lapatinib Ditosylate

Lapatinib Ditosylate is a potent EGFR and ErbB2 inhibitor with IC50 of 10.8 and 9.2 nM in cell-free assays, respectively.

Lapatinib

Lapatinib, used in the form of Lapatinib Ditosylate, is a potent EGFR and ErbB2 inhibitor with IC50 of 10.8 and 9.2 nM in cell-free assays, respectively. Lapatinib induces ferroptosis and autophagic cell death.

Afatinib

Afatinib inhibits EGFR/ErbB irreversibly in vitro with IC50 of 0.5, 0.4, 10, 14, 1 nM for EGFR^wt, EGFR ^L858R , EGFR ^L858R/T790M ErbB2 (HER2) and ErbB4 (HER4), respectively. Afatinib induces autophagy.

Afatinib Dimaleate

Afatinib Dimaleate irreversibly inhibits EGFR/HER2 including EGFR(wt), EGFR(L858R), EGFR(L858R/T790M) and HER2 with IC50 of 0.5 nM, 0.4 nM, 10 nM and 14 nM, respectively; 100-fold more active against Gefitinib-resistant L858R-T790M EGFR mutant. Afatinib (BIBW2992) Dimaleate induces autophagy.

CUDC-101

CUDC-101 is a potent multi-targeted inhibitor against HDAC, EGFR and HER2 with IC50 of 4.4 nM, 2.4 nM, and 15.7 nM, and inhibits class I/II HDACs, but not class III, Sir-type HDACs. Phase 1.

TAK-285

TAK-285 is a novel dual HER2 and EGFR(HER1) inhibitor with IC50 of 17 nM and 23 nM, >10-fold selectivity for HER1/2 than HER4, less potent to MEK1/5, c-Met, Aurora B, Lck, CSK etc. Phase 1.

AV-412 free base

AV-412 free base (MP-412 free base) is an EGFR inhibitor with IC50s of 0.75, 0.51, 0.79, 2.30, 19 nM for EGFR, EGFR^L858R, EGFR^T790M, EGFR^L858R/T790M and ErbB2, respectively.

AC480 (BMS-599626)

AC480 (BMS-599626) is a selective and efficacious inhibitor of HER1 and HER2 with IC50 of 20 nM and 30 nM, ~8-fold less potent to HER4, >100-fold to VEGFR2, c-Kit, Lck, MET etc. Phase 1.

Pyrotinib dimaleate

Pyrotinib dimaleate is a potent and selective irreversible dual tyrosine kinase inhibitor of EGFR and HER2 with IC50 of 0.013 μM and 0.038 μM, respectively.

Dacomitinib

Dacomitinib is a potent, irreversible pan-ErbB inhibitor, mostly to EGFR with IC50 of 6 nM in a cell-free assay. Dacomitinib inhibits ERBB2 and ERBB4 with IC50 of 45.7 nM and 73.7 nM, respectively. Dacomitinib is effective against NSCLCs with EGFR or ERBB2 mutations (resistant to gefitinib) as well as those harboring the EGFR T790M mutation. Dacomitinib inhibits cell growth and induces apoptosis. Phase 2.

Neratinib

Neratinib is a highly selective HER2 and EGFR inhibitor with IC50 of 59 nM and 92 nM in cell-free assays; weakly inhibits KDR and Src, no significant inhibition to Akt, CDK1/2/4, IKK-2, MK-2, PDK1, c-Raf and c-Met. Phase 3.

Pelitinib (EKB-569)

Pelitinib (EKB-569) is a potent irreversible EGFR inhibitor with IC50 of 38.5 nM. Pelitinib (EKB-569) also slightly inhibits Src, MEK/ERK and ErbB2 with IC50s of 282 nM, 800 nM and 1255 nM, respectively. Phase2.

Tyrphostin AG-528

Tyrphostin AG-528 (Tyrphostin B66) is a potent inhibitor of epidermal growth factor receptors (EGFR) and ErbB2/HER2 with IC50 of 4.9 μM and 2.1 μM, respectively. Tyrphostin AG-528 exhibits anticancer activity.

EGCG ((-)-Epigallocatechin Gallate)

EGCG ((-)-Epigallocatechin Gallate) is the main catechin extraction of green tea that inhibits telomerase and DNA methyltransferase. EGCG blocks the activation of EGF receptors and HER-2 receptors. ECGG inhibits fatty acid synthase and glutamate dehydrogenase activity.

Mobocertinib (TAK788)

Mobocertinib (TAK788, AP32788), an investigational TKI, is a potent, selective preclinical inhibitor of epidermal growth factor receptor (EGFR) and HER2 mutations. Mobocertinib (TAK788) is an antineoplastic agent.