Target family: Type I RTKs: ErbB (epidermal growth factor) receptor family (type: catalytic_receptor)
Target: erb-b2 receptor tyrosine kinase 2

Ligand: acalabrutinib (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: yes
Approval source: FDA (2017), EMA (2020)
Primary target: no
Median affinity: 6 pIC50
Reference (Journal): Acalabrutinib (ACP-196) in Relapsed Chronic Lymphocytic Leukemia.
Published in: N Engl J Med

Ligand: AEE788 (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 8.220000267028809 pIC50
Reference (Journal): AEE788: a dual family epidermal growth factor receptor/ErbB2 and vascular endothelial growth factor receptor tyrosine kinase inhibitor with antitumor and antiangiogenic activity.
Published in: Cancer Res

Ligand: afatinib (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: yes
Approval source: EMA & FDA (2013)
Primary target: no
Median affinity: 7.849999904632568 pIC50
Reference (Journal): BIBW2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models.
Published in: Oncogene

Ligand: allitinib (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 8.520000457763672 pIC50
Reference (Journal): AST1306, a novel irreversible inhibitor of the epidermal growth factor receptor 1 and 2, exhibits antitumor activity both in vitro and in vivo.
Published in: PLoS ONE

Ligand: BI-4142 (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 7.090000152587891 pIC50
Reference (Journal): Discovery of potent and selective HER2 inhibitors with efficacy against HER2 exon 20 insertion-driven tumors, which preserve wild-type EGFR signaling.
Published in: Nat Cancer

Ligand: BI-4142 (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 8 pIC50
Reference (Journal): Discovery of potent and selective HER2 inhibitors with efficacy against HER2 exon 20 insertion-driven tumors, which preserve wild-type EGFR signaling.
Published in: Nat Cancer

Ligand: BMS-599626 (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 7.489999771118164 pIC50
Reference (Journal): Discovery and preclinical evaluation of [4-[[1-(3-fluorophenyl)methyl]-1H-indazol-5-ylamino]-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yl]carbamic acid, (3S)-3-morpholinylmethyl ester (BMS-599626), a selective and orally efficacious inhibitor of human epidermal growth factor receptor 1 and 2 kinases.
Published in: J Med Chem

Ligand: BMS-690514 (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: yes
Median affinity: 7.71999979019165 pIC50
Reference (Journal): Preclinical pharmacokinetics and in vitro metabolism of BMS-690514, a potent inhibitor of EGFR and VEGFR2.
Published in: J Pharm Sci

Ligand: canertinib (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 8.050000190734863 pIC50
Reference (Journal): Tyrosine kinase inhibitors. 17. Irreversible inhibitors of the epidermal growth factor receptor: 4-(phenylamino)quinazoline- and 4-(phenylamino)pyrido[3,2-d]pyrimidine-6-acrylamides bearing additional solubilizing functions.
Published in: J Med Chem

Ligand: compound 38 [PMID: 24915291] (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 8.149999618530273 pIC50
Reference (Journal): Discovery of a series of 2,5-diaminopyrimidine covalent irreversible inhibitors of Bruton's tyrosine kinase with in vivo antitumor activity.
Published in: J Med Chem

Ligand: CP-724714 (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: yes
Median affinity: 7.920000076293945 pIC50
Reference (Journal): Discovery of novel small-molecule inhibitors of human epidermal growth factor receptor-2: combined ligand and target-based approach.
Published in: J Med Chem

Ligand: CUDC-101 (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 7.800000190734863 pIC50
Reference (Journal): Discovery of 7-(4-(3-ethynylphenylamino)-7-methoxyquinazolin-6-yloxy)-N-hydroxyheptanamide (CUDc-101) as a potent multi-acting HDAC, EGFR, and HER2 inhibitor for the treatment of cancer.
Published in: J Med Chem

Ligand: dacomitinib (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: yes
Approval source: FDA (2018), EMA (2019)
Primary target: no
Median affinity: 7.340000152587891 pIC50
Reference (Journal): Irreversible protein kinase inhibitors: balancing the benefits and risks.
Published in: J Med Chem

Ligand: EGFR/ErbB-2/ErbB-4 inhibitor (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: yes
Median affinity: 8.960000038146973 pIC50
Reference (Journal): Tyrosine kinase inhibitors. 19. 6-Alkynamides of 4-anilinoquinazolines and 4-anilinopyrido[3,4-d]pyrimidines as irreversible inhibitors of the erbB family of tyrosine kinase receptors.
Published in: J Med Chem

Ligand: EGFR/ErbB-2 inhibitor (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: yes
Median affinity: 7.099999904632568 pIC50
Reference (Journal): Indazolylamino quinazolines and pyridopyrimidines as inhibitors of the EGFr and C-erbB-2.
Published in: Bioorg Med Chem Lett

Ligand: falnidamol (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 5.46999979019165 pIC50
Reference (Journal): Inhibition of epidermal growth factor receptor activity by two pyrimidopyrimidine derivatives.
Published in: J Pharmacol Exp Ther

Ligand: ibrutinib (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: yes
Approval source: FDA (2013), EMA (2014)
Primary target: no
Median affinity: 8.1899995803833 pIC50
Reference (Journal): Acalabrutinib (ACP-196) in Relapsed Chronic Lymphocytic Leukemia.
Published in: N Engl J Med

Ligand: lapatinib (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: yes
Approval source: FDA (2007), EMA (2008)
Primary target: yes
Median affinity: 8 pIC50
Reference (Journal): The effects of the novel, reversible epidermal growth factor receptor/ErbB-2 tyrosine kinase inhibitor, GW2016, on the growth of human normal and tumor-derived cell lines in vitro and in vivo.
Published in: Mol Cancer Ther

Ligand: lapatinib (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: yes
Approval source: FDA (2007), EMA (2008)
Primary target: yes
Median affinity: 8.149999618530273 pKd
Reference (Journal): Comprehensive analysis of kinase inhibitor selectivity.
Published in: Nat Biotechnol

Ligand: margetuximab (Antibody)
Interaction type: Antibody
Action: Binding
Ligand approved: yes
Approval source: FDA (2020)
Primary target: yes
Median affinity:  -
Reference (Patent): HER2/neu-specific antibodies and methods of using same.

Ligand: mifanertinib (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 7.929999828338623 pIC50
Reference (Patent): Aminoquinazoline derivative and use thereof in preparing anti-malignant tumor medicament

Ligand: MM-111 (Antibody)
Interaction type: Antibody
Action: Binding
Ligand approved: no
Primary target: yes
Median affinity: 9.520000457763672 pKd
Reference (Journal): Antitumor activity of a novel bispecific antibody that targets the ErbB2/ErbB3 oncogenic unit and inhibits heregulin-induced activation of ErbB3.
Published in: Mol Cancer Ther

Ligand: mubritinib (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: yes
Median affinity: 8.220000267028809 pIC50
Reference (Journal): Novel HER2 selective tyrosine kinase inhibitor, TAK-165, inhibits bladder, kidney and androgen-independent prostate cancer in vitro and in vivo.
Published in: Int J Urol

Ligand: neratinib (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: yes
Approval source: FDA (2017), EMA (2018)
Primary target: yes
Median affinity: 7.230000019073486 pIC50
Reference (Journal): Antitumor activity of HKI-272, an orally active, irreversible inhibitor of the HER-2 tyrosine kinase.
Published in: Cancer Res

Ligand: neratinib (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: yes
Approval source: FDA (2017), EMA (2018)
Primary target: yes
Median affinity: 8.220000267028809 pKd
Reference (Journal): Comprehensive analysis of kinase inhibitor selectivity.
Published in: Nat Biotechnol

Ligand: pertuzumab (Antibody)
Interaction type: Antibody
Action: Inhibition
Ligand approved: yes
Approval source: FDA (2012), EMA (2013)
Primary target: yes
Median affinity: 8 pIC50
Reference (Patent): Her2 antibody composition.

Ligand: pirotinib (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 8.1899995803833 pIC50
Reference (Patent): Quinazoline derivatives substituted by aniline, preparation method and use thereof

Ligand: poziotinib (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: yes
Median affinity: 8.279999732971191 pIC50
Reference (Journal): Antitumor activity of HM781-36B, an irreversible Pan-HER inhibitor, alone or in combination with cytotoxic chemotherapeutic agents in gastric cancer.
Published in: Cancer Lett

Ligand: pyrotinib (Synthetic organic)
Interaction type: Inhibitor
Action: Irreversible inhibition
Ligand approved: yes
Approval source: China (2018)
Primary target: no
Median affinity: 7.420000076293945 pIC50
Reference (Journal): Discovery and development of pyrotinib: A novel irreversible EGFR/HER2 dual tyrosine kinase inhibitor with favorable safety profiles for the treatment of breast cancer.
Published in: Eur J Pharm Sci

Ligand: sapitinib (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: yes
Median affinity: 7.849999904632568 pIC50
Reference (Journal): Discovery of AZD8931, an Equipotent, Reversible Inhibitor of Signaling by EGFR, HER2, and HER3 Receptors.
Published in: ACS Med Chem Lett

Ligand: selatinib (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 8.069999694824219 pIC50
Reference (Journal): Discovery of a potent dual EGFR/HER-2 inhibitor L-2 (selatinib) for the treatment of cancer.
Published in: Eur J Med Chem

Ligand: tesevatinib (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: yes
Median affinity: 7.800000190734863 pIC50
Reference (Journal): Inhibition of the T790M gatekeeper mutant of the epidermal growth factor receptor by EXEL-7647.
Published in: Clin Cancer Res

Ligand: trastuzumab (Antibody)
Interaction type: Antibody
Action: Inhibition
Ligand approved: yes
Approval source: FDA (1998), EMA (2000)
Primary target: yes
Median affinity:  -

Ligand: tucatinib (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: yes
Approval source: FDA (2020), EMA (2021)
Primary target: yes
Median affinity: 8.15999984741211 pIC50
Reference (Journal): Preclinical Activity of HER2-Selective Tyrosine Kinase Inhibitor Tucatinib as a Single Agent or in Combination with Trastuzumab or Docetaxel in Solid Tumor Models.
Published in: Mol Cancer Ther

Ligand: tuxobertinib (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity:  pIC50
Reference (Patent): Tyrosine kinase inhibitor compositions, methods of making and methods of use

Ligand: zongertinib (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 7.889999866485596 pIC50
Reference (Patent): [1,3]diazino[5,4-d]pyrimidines as her2 inhibitors