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Neratinib (HKI-272; PB272; Nerlynx)

Alias: Neratinib; HKI-272; PB272; HKI272; PB 272; HKI 272; 698387-09-6; HKI-272; Neratinib (HKI-272); Nerlynx; HKI 272; UNII-JJH94R3PWB; JJH94R3PWB; PB-272; trade name: Nerlynx
Cat No.:V0537 Purity: ≥98%
Neratinib (formerly known as HKI-272 or PB-272; trade name:Nerlynx)is a highly potent, selective, and orally bioavailable HER2 and EGFR inhibitor with potential antitumor activity.
Neratinib (HKI-272; PB272; Nerlynx)
Neratinib (HKI-272; PB272; Nerlynx) Chemical Structure CAS No.: 698387-09-6
Product category: EGFR
This product is for research use only, not for human use. We do not sell to patients.
Size Price Stock Qty
10mg
25mg
50mg
100mg
250mg
500mg
1g
Other Sizes

Other Forms of Neratinib (HKI-272; PB272; Nerlynx):

  • NERATINIB MALEATE
  • Neratinib-d6 (neratinib d6)
Official Supplier of:
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Purity & Quality Control Documentation

Purity: ≥98%

Product Description

Neratinib (formerly known as HKI-272 or PB-272; trade name: Nerlynx) is a highly potent, selective, and orally bioavailable HER2 and EGFR inhibitor with potential antitumor activity. In cell-free assays, it inhibits HER2 and EGFR with IC50s of 59 nM and 92 nM, respectively. The FDA gave it approval in 2017 to treat breast cancer. Neratinib exhibits no discernible inhibition of Akt, CDK1/2/4, IKK-2, MK-2, PDK1, c-Raf, and c-Met, and it only weakly inhibits KDR and Src.

Biological Activity I Assay Protocols (From Reference)
Targets
HER2 (IC50 = 59 nM); EGFR (IC50 = 92 nM); KDR (IC50 = 800 nM); Src (IC50 = 1.4 μM)
ln Vitro
Neratinib shows no action against tyrosine kinase c-Met[1], Akt, cyclin D1/cdk4, cyclin E/cdk2, cyclin B1/cdk1, IKK-2, MK-2, PDK1, c-Raf, and Tpl-2, among other serine-threonine kinases[1].
Neratinib is much less active in cell lines that express neither EGFR nor HER-2 (3T3, MDA-MB-435, and SW620), and it inhibits the proliferation of cell lines that exhibit high levels of HER-2 (3T3/neu, SK-Br-3, and BT474)[1].
Neratinib (0-2 nM, 12-16 h) arrests BT474 cell cycle at G1-S phase[1].
Neratinib causes cyclin D1 levels to be down-regulated, Akt and MAPK phosphorylation to be inhibited, and p27 to be induced[1].
ln Vivo
Neratinib (HKI-272) exhibits anticancer properties against cancer cells that express high levels of EGFR or HER-2 (0-80 mg/kg/day; i.e., 42 days)[1].
In vivo, HKI-272 is active in HER-2- and EGFR-dependent tumor xenograft models when dosed orally on a once daily schedule. On the basis of its favorable preclinical pharmacological profile, HKI-272 has been selected as a candidate for additional development as an antitumor agent in breast and other HER-2-dependent cancers.[1]
Enzyme Assay
Prepared as 10 mg/mL stocks in DMSO, neratinib is diluted in 25 mM HEPES (pH 7.5; 0.002 ng/mL–20 μg/mL). In 96-well ELISA plates, purified recombinant COOH-terminal fragments of HER2 (amino acids 676-1255) or epidermal growth factor receptor (EGFR) (amino acids 645-1186) are diluted in 100 mM HEPES (pH 7.5) and 50% glycerol. The mixture is then incubated with increasing concentrations of Neratinib in 4 mM HEPES (pH 7.5), 0.4 mM MnCl2, 20 μM sodium vanadate, and 0.2 mM DTT for 15 minutes at room temperature. 40 μM ATP and 20 mM MgCl2 are added to start the kinase reaction, which is then left to run at room temperature for an hour. Wash the plates, then use anti-phospho-tyrosine antibodies (15 ng/well) labeled with europium to detect phosphorylation. Using a Victor2 fluorescence reader (excitation wavelength of 340 nm and emission wavelength of 615 nm), the signal is detected following the washing and enhancement stages. An inhibition curve is used to determine the concentration of Neratinib (IC50) at which receptor phosphorylation is inhibited by 50%.
Activity of HER-2 and EGFR cytoplasmic domains was measured by an autophosphorylation assay using time-resolved fluorometry. Compounds were prepared as 10 mg/ml stocks in DMSO and diluted in 25 mm HEPES (pH 7.5; 0.002 ng/ml–20 μg/ml). Enzyme [diluted in 100 mm HEPES (pH 7.5) and 50% glycerol] was incubated with inhibitor in 4 mm HEPES (pH 7.5), 0.4 mm MnCl2, 20 μm sodium vanadate, and 0.2 mm DTT for 15 min at room temperature in 96-well ELISA plates. The kinase reaction was initiated by the addition of 40 μm ATP and 20 mm MgCl2 and allowed to proceed for 1 h at room temperature. Plates were washed, and phosphorylation was detected using Europium-labeled anti-phospho-tyrosine antibodies (15 ng/well; Wallac). After washing and enhancement steps according to the manufacturer’s recommendations, signal was detected using a Victor2 fluorescence reader (excitation wavelength 340 nm, emission wavelength 615 nm). The concentration of compound that inhibited receptor phosphorylation by 50% (IC50) was calculated from inhibition curves.[1]
Assays for other kinases were performed using recombinant enzymes expressed in bacterial, insect, or human cell lines. All enzymes used were serine-threonine kinases, except c-Met, KDR, src (tyrosine kinases), and MEK1 (dual specificity). Substrates used were peptides (Akt, IKK-2, MK2, PDK1, src, and Tpl2), proteins (cyclin D1/CDK4, cyclin E/CDK2, cyclin B1/CDK1, and c-Raf), poly(glutamic acid4-tyrosine) (KDR), or the kinase itself (autophosphorylation; c-met). Phosphorylation was measured using TMB peroxidase substrate for cyclin/cyclin-dependent kinase (cdk), LabChip for MK-2, or DELPHIA/LANCE for all others.[1]
Cell Assay
Different concentrations of Neratinib are applied to cells (3T3, 3T3/neu, A431, BT474, SK-Br-3, MDA-MB-435, and SW480) for a period of either two or six days. A protein-binding dye called sulforhodamine B is used to measure cell proliferation. In short, cells are thoroughly cleaned with water after being fixed with 10% trichloroacetic acid. After staining the cells with 0.1% sulforhodamine B, they are rinsed in 5% acetic acid. After solubilizing the protein-associated dye in 10 mM Tris, the absorbance is calculated at 450 nM. Inhibition curves are used to calculate the concentration of neratinib (IC50) that inhibits cell proliferation by 50%.
Animal Protocol
Female athymic (nude) mice, tumor xenograft[1]
10, 20, 40, 60 or 80 mg/kg/day
Gavage, 42 days
Tumor Xenograft Studies.[1]
Tumor cells (maintained in tissue culture) or tumor fragments were implanted s.c. in the flanks of female athymic (nude) mice. For estrogen-dependent cell lines (BT474, MCF-7, and SK-OV-3), animals were implanted with hormone pellets (0.72 mg of 17-β estradiol, 60-day release) 1 week before implantation of tumors. Additionally, SK-OV-3 cells were suspended in Matrigel basement membrane matrix for implantation. Treatment was initiated after tumors had reached a size of 90–200 mg, following random assignment of the animals to different treatment groups (staging, day 0). For 3T3/neu xenografts, treatment was initiated the day after tumor implantation (day 0). HKI-272 was formulated in 0.5% methocellulose-0.4% polysorbate-80 (Tween 80) and administered daily, p.o., by gavage. Tumor mass [(length × width2)/2] was determined every 7 days. Tumor outgrowth in all xenograft studies, except 3T3/neu, was expressed as relative tumor growth: the ratio of the mean tumor mass to the mean tumor mass on day 0. Inhibition of tumor growth was calculated relative to vehicle-treated controls. Statistical significance of inhibition was demonstrated using one-tailed Student’s t test (equal variance) after log transformation of the data.[1]
HER-2 Phosphorylation in Xenografts.[1]
Athymic female nude mice (5 animals/group) were implanted s.c. with BT474 tumor fragments (∼30 mm3). When tumors reached 200–300 mg, animals were given a single oral dose (40 mg/kg) of HKI-272 in pH 2.0 water. Tumors from control and treated animals were excised at 1, 3, 6, and 24 h and minced. Tumor fragments were suspended in 10 mm Tris (pH 7.5), 5 mm EDTA, 150 mm NaCl, 1% Triton X-100, 1% sodium deoxycholate, 0.1% SDS, 1 mm phenylmethylsulfonyl fluoride, 10 μg/ml pepstatin, 10 μg/ml leupeptin, 10 μg/ml aprotinin, 2 mm sodium vanadate, and 100 mm sodium fluoride and lysed by homogenization on ice with a polytron. After clarification by centrifugation, protein concentration in lysates was estimated using the Bio-Rad DC protein assay. Sixty μg of lysate pooled from each group were analyzed by SDS-PAGE and immunoblotting with phospho-tyrosine-specific antibodies. Pooled extracts were also immunoprecipitated using 4 μg of anti-HER-2 antibodies for 1 h at 4°C. Immune complexes were collected on protein A-agarose, washed, and analyzed by immunoblotting using phospho-tyrosine-specific antibodies. Extracts from individual tumors were analyzed to determine variability between animals.
ADME/Pharmacokinetics
Absorption, Distribution and Excretion
Neratinib and its major active metabolites M3. M6, and M7 have a Tmax of 2-8 h. Administration with a high fat meal increases Cmax by 1.7-fold and total exposure by 2.2-fold. Administration with a standard meal increases Cmax by 1.2-fold and total exposure by 1.1-fold. Administration with gastric acid reducing agents such as proton pump inhibitors reduces Cmax by 71% and total exposure by 65%.
97.1% of the total dose is excreted in the feces and 1.13% in the urine.
The apparent volume of distribution at steady state is 6433 L.
The total clearance during multiple doses is 216 L/h for after the first dose and 281 L/h during steady state.
Metabolism / Metabolites
Neratinib is mainly undergoes metabolism via CYP3A4. It is also metabolized by flavin-containing monooxygenase to a lesser extent. The systemic exposures of neratinib's active metabolites M3, M6, M7, and M11 are 15%, 33%, 22%, and 4%.
Biological Half-Life
The mean half life of elimination ranges from 7-17 h following a single dose. The mean plasma half life during multiple doses is 14.6 h for neratinib, 21.6 h for M3, 13.8 h for M6, and 10.4 h for M7.
Toxicity/Toxicokinetics
Hepatotoxicity
Elevations in serum aminotransferase levels are not uncommon during neratinib therapy occurring in up to 10% of patients, but rising above 5 times the upper limit of the normal range in only 1% to 2%. In prelicensure studies, there were no instances of neratinib related clinically apparent liver injury and serum enzyme elevations were typically mild and self-limited and not associated with symptoms or jaundice. Hepatotoxicity may be a class effect among protein kinase inhibitors of HER2, although the frequency and severity vary among the different agents. Specific details of the liver injury associated with neratinib such as latency, serum enzyme pattern, clinical features and course, have not been published. Other tyrosine kinase receptor inhibitors typically cause liver injury arising within days or weeks of starting therapy and presenting abruptly with hepatocellular enzyme elevations and a moderate-to-severe course. Immunoallergic and autoimmune features are not common. The rate of clinically significant liver injury and hepatic failure is increased in patients with preexisting cirrhosis or hepatic impairment due to liver tumor burden. Nevertheless, neratinib has not been convincingly linked to instances of clinically apparent liver injury.
Likelihood score: E* (unproven but suspected cause of clinically apparent liver injury).
Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
No information is available on the clinical use of neratanib during breastfeeding. Because neratanib and its metabolite are over 99% bound to plasma proteins, the amount in milk is likely to be low. The manufacturer recommends that breastfeeding be discontinued during neratanib therapy.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.
Protein Binding
Neratinib is over 99% bound to human plasma proteins. It binds both human serum albumin and α1 acid glycoprotein.
References

[1]. Antitumor activity of HKI-272, an orally active, irreversible inhibitor of the HER-2 tyrosine kinase. Cancer Res, 2004, 64(11), 3958-3965.

Additional Infomation
Neratinib is a quinoline compound having a cyano group at the 3-position, a 3-chloro-4-(2-pyridylmethoxy)anilino group at the 4-position, a 4-dimethylamino-trans-but-2-enoylamido group at the 6-position, and an ethoxy group at the 7-position. It has a role as a tyrosine kinase inhibitor and an antineoplastic agent. It is a member of quinolines and a nitrile.
Neratinib was approved in July 2017 for use as an extended adjuvant therapy in Human Epidermal Growth Factor Receptor 2 (HER2) positive breast cancer. Approval was granted to Puma Biotechnology Inc. for the tradename Nerlynx. Neratinib is currently under investigation for use in many other forms of cancer.
Neratinib is a Kinase Inhibitor. The mechanism of action of neratinib is as a Kinase Inhibitor, and P-Glycoprotein Inhibitor.
Neratinib is an orally available tyrosine kinase receptor inhibitor that is used in the extended adjuvant therapy of early stage breast cancer. Neratinib is associated with a low rate of transient elevations in serum aminotransferase levels during therapy, but has not been convincingly linked to cases of clinically apparent liver injury with jaundice.
Neratinib is an orally available, 6,7-disubstituted-4-anilinoquinoline-3-carbonitrile irreversible inhibitor of the HER-2 receptor tyrosine kinase with potential antineoplastic activity. Neratinib binds to the HER-2 receptor irreversibly, thereby reducing autophosphorylation in cells, apparently by targeting a cysteine residue in the ATP-binding pocket of the receptor. Treatment of cells with this agent results in inhibition of downstream signal transduction events and cell cycle regulatory pathways; arrest at the G1-S (Gap 1/DNA synthesis)-phase transition of the cell division cycle; and ultimately decreased cellular proliferation. Neratinib also inhibits the epidermal growth factor receptor (EGFR) kinase and the proliferation of EGFR-dependent cells.
See also: Neratinib Maleate (active moiety of).
Drug Indication
For use as an extended adjuvant treatment in adult patients with early stage HER2-overexpressed/amplified breast cancer, to follow adjuvant trastuzumab-based therapy.
FDA Label
Nerlynx is indicated for the extended adjuvant treatment of adult patients with early stage hormone receptor positive HER2-overexpressed/amplified breast cancer and who are less than one year from the completion of prior adjuvant trastuzumab based therapy.
Treatment of breast cancer
Mechanism of Action
Neratinib binds to and irreversibly inhibits EGFR, HER2, and HER4. This prevents auotphoshorylation of tyrosine residues on the receptor and reduces oncogenic signalling through the mitogen-activated protein kinase and Akt pathways.
Pharmacodynamics
Neratinib is a tyrosine kinase inhibitor which exhibits antitumor action against Epidermal Growth Factor Receptor (EGFR), HER2, and Human Epidermal Growth Factor Receptor 4 (HER4) postive carcinomas.
These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C30H29CLN6O3
Molecular Weight
557.04
Exact Mass
556.198
Elemental Analysis
C, 64.68; H, 5.25; Cl, 6.36; N, 15.09; O, 8.62
CAS #
698387-09-6
Related CAS #
Neratinib maleate;915942-22-2;Neratinib-d6;1259519-18-0
PubChem CID
9915743
Appearance
White to light brown solid powder
Density
1.3±0.1 g/cm3
Boiling Point
757.0±60.0 °C at 760 mmHg
Melting Point
184 °C
Flash Point
411.6±32.9 °C
Vapour Pressure
0.0±2.5 mmHg at 25°C
Index of Refraction
1.667
LogP
5.46
Hydrogen Bond Donor Count
2
Hydrogen Bond Acceptor Count
8
Rotatable Bond Count
11
Heavy Atom Count
40
Complexity
881
Defined Atom Stereocenter Count
0
SMILES
ClC1=C(C([H])=C([H])C(=C1[H])N([H])C1=C(C#N)C([H])=NC2=C([H])C(=C(C([H])=C12)N([H])C(/C(/[H])=C(\[H])/C([H])([H])N(C([H])([H])[H])C([H])([H])[H])=O)OC([H])([H])C([H])([H])[H])OC([H])([H])C1=C([H])C([H])=C([H])C([H])=N1
InChi Key
JWNPDZNEKVCWMY-VQHVLOKHSA-N
InChi Code
InChI=1S/C30H29ClN6O3/c1-4-39-28-16-25-23(15-26(28)36-29(38)9-7-13-37(2)3)30(20(17-32)18-34-25)35-21-10-11-27(24(31)14-21)40-19-22-8-5-6-12-33-22/h5-12,14-16,18H,4,13,19H2,1-3H3,(H,34,35)(H,36,38)/b9-7+
Chemical Name
(E)-N-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]-3-cyano-7-ethoxyquinolin-6-yl]-4-(dimethylamino)but-2-enamide
Synonyms
Neratinib; HKI-272; PB272; HKI272; PB 272; HKI 272; 698387-09-6; HKI-272; Neratinib (HKI-272); Nerlynx; HKI 272; UNII-JJH94R3PWB; JJH94R3PWB; PB-272; trade name: Nerlynx
HS Tariff Code
2934.99.9001
Storage

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
Solubility (In Vitro)
DMSO: 3~12 mg/mL (vary from batch to batch)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In Vivo)
Solubility in Formulation 1: 2 mg/mL (3.59 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

Solubility in Formulation 2: ≥ 0.83 mg/mL (1.49 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 8.3 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 3: 30% PEG400+0.5% Tween80+5% propylene glycol: 5 mg/mL


Solubility in Formulation 4: 3.33 mg/mL (5.98 mM) in 0.5% MC 0.5% Tween-80 (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.

 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 1.7952 mL 8.9760 mL 17.9520 mL
5 mM 0.3590 mL 1.7952 mL 3.5904 mL
10 mM 0.1795 mL 0.8976 mL 1.7952 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

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Clinical Trial Information
Neratinib and Capmatinib Combination (Phase Ib/II) in Metastatic Breast Cancer and Inflammatory Breast Cancer Patients With Abnormal HER-family and c-Met Pathway Activity as Measured by the CELsignia Signaling Analysis Test
CTID: NCT05243641
Phase: Phase 1/Phase 2    Status: Terminated
Date: 2024-11-27
Personalized Medicine for Advanced Biliary Cancer Patients
CTID: NCT05615818
Phase: Phase 3    Status: Recruiting
Date: 2024-11-26
Three Antidiarrheal Strategies in HER2+/HR+ Early Breast Cancer Patients Treated With Extended Adjuvant Neratinib
CTID: NCT05252988
Phase: Phase 2    Status: Active, not recruiting
Date: 2024-11-20
Neoadjuvant Neratinib in Stage I-III HER2-Mutated Lobular Breast Cancers
CTID: NCT05919108
Phase: Phase 2    Status: Recruiting
Date: 2024-11-20
Adjuvant Therapy With Neratinib in HER2 Positive Early Breast Cancer
CTID: NCT06693024
Phase:    Status: Recruiting
Date: 2024-11-20
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Innovative Trial for Understanding the Impact of Targeted Therapies in NF2-Related Schwannomatosis (INTUITT-NF2)
CTID: NCT04374305
Phase: Phase 2    Status: Active, not recruiting
Date: 2024-11-18


Neratinib + Valproate in Advanced Solid Tumors, w/Expansion Cohort in Ras-Mutated Ca
CTID: NCT03919292
Phase: Phase 1/Phase 2    Status: Recruiting
Date: 2024-11-06
Safety and Dose Finding Study of Neratinib in Children and Young Adults With Cancer That Has Returned or Not Responded to Treatment
CTID: NCT02932280
Phase: Phase 1/Phase 2    Status: Active, not recruiting
Date: 2024-11-05
Niraparib and Neratinib in Advanced Solid Tumors With Expansion Cohort in Advanced Ovarian Cancer
CTID: NCT04502602
Phase: Phase 1    Status: Recruiting
Date: 2024-10-29
I-SPY TRIAL: Neoadjuvant and Personalized Adaptive Novel Agents to Treat Breast Cancer
CTID: NCT01042379
Phase: Phase 2    Status: Recruiting
Date: 2024-10-22
INdividualized Screening Trial of Innovative Glioblastoma Therapy (INSIGhT)
CTID: NCT02977780
Phase: Phase 2    Status: Recruiting
Date: 2024-10-17
Trial of Pre-operative Neratinib and Endocrine Therapy With Trastuzumab in ER-Positive, HER-2 Positive Breast Cancers
CTID: NCT04886531
Phase: Phase 2    Status: Recruiting
Date: 2024-10-15
Neratinib in Combination With Ruxolitinib in Patients With mTNBC
CTID: NCT06008275
PhaseEarly Phase 1    Status: Recruiting
Date: 2024-10-09
Neratinib In Combination With Chemotherapy/Trastuzumab/Pembrolizumab In HER2 Gastroesophageal Cancer
CTID: NCT06109467
Phase: Phase 2    Status: Recruiting
Date: 2024-09-19
Neratinib Tablets Monotherapy for Advanced Solid Tumors With HER2 Mutations
CTID: NCT06519110
Phase: Phase 2    Status: Not yet recruiting
Date: 2024-07-25
Neratinib and Everolimus, Palbociclib, or Trametinib in Treating Participants With Refractory and Advanced or Metastatic Solid Tumors With EGFR Mutation/Amplification, HER2 Mutation/Amplification, or HER3/4 Mutation or KRAS Mutation
CTID: NCT03065387
Phase: Phase 1    Status: Active, not recruiting
Date: 2024-06-26
Neratinib and Paclitaxel With or Without Pertuzumab and Trastuzumab Before Combination Chemotherapy in Treating Patients With Metastatic or Locally Advanced Breast Cancer
CTID: NCT03101748
Phase: Phase 1/Phase 2    Status: Active, not recruiting
Date: 2024-06-03
HKI-272 for HER2-Positive Breast Cancer and Brain Metastases
CTID: NCT01494662
Phase: Phase 2    Status: Active, not recruiting
Date: 2024-05-22
-
An Open Label Study to Characterize the Incidence and Severity of Diarrhea in Patients with Early Stage HER2+ Breast Cancer Treated with Neratinib and Intensive Loperamide Prophylaxis
CTID: null
Phase: Phase 2    Status: Completed
Date: 2018-04-13
A Phase 2 Study of Neratinib and Neratinib Plus Temsirolimus in Patients with Non-Small Cell Lung Cancer Carrying Known HER2 Activating Mutations
CTID: null
Phase: Phase 2    Status: Completed
Date: 2014-05-06
An Open-Label, Phase 2 Basket Study of Neratinib in Patients With Solid Tumors With Somatic Activation HER Mutations
CTID: null
Phase: Phase 2    Status: Ongoing, GB - no longer in EU/EEA, Completed
Date: 2014-03-25
A Phase II Randomized Clinical Trial Evaluating Neoadjuvant Therapy Regimens with Weekly Paclitaxel plus Neratinib or Trastuzumab or Neratinib and Trastuzumab Followed by Doxorubicin and Cyclophosphamide with Postoperative Trastuzumab in Women with Locally Advanced HER2-Positive Breast Cancer.
CTID: null
Phase: Phase 2    Status: Completed
Date: 2014-02-18
A Phase I/II Trial of Temsirolimus Plus Neratinib for Patients with Metastatic HER2-Amplified or Triple-Negative Breast Cancer
CTID: null
Phase: Phase 1, Phase 2    Status: Completed
Date: 2013-10-02
A Study of Neratinib Plus Capecitabine Versus Lapatinib Plus Capecitabine in Patients With HER2+ Metastatic Breast Cancer Who Have Received Two or More Prior HER2-Directed Regimens in the Metastatic Setting (NALA)
CTID: null
Phase: Phase 3    Status: Prematurely Ended, Completed
Date: 2013-07-30
A Randomized, Open-Label, Two-Arm Study of Neratinib Plus Paclitaxel Versus Trastuzumab Plus Paclitaxel as First-Line Treatment for ErbB-2-Positive Locally Recurrent or Metastatic Breast Cancer
CTID: null
Phase: Phase 2    Status: Completed
Date: 2009-08-26
A Randomized Double-blind Placebo-Controlled Trial of Neratinib (HKI-272) After Trastuzumab in Women With Early-Stage HER-2/neu Overexpressed/Amplified Breast Cancer.
CTID: null
Phase: Phase 3    Status: Completed
Date: 2009-08-05
A Phase 2 Randomized Open Label Study of Neratinib versus Lapatinib plus Capecitabine for the Treatment of ErbB-2 Positive Locally Advanced or Metastatic Breast Cancer
CTID: null
Phase: Phase 2    Status: Prematurely Ended, Completed
Date: 2009-01-14
Phase 1/2 Randomized, Open-label, Three Arm Study of Neratinib (HKI-272) vs. Neratinib + Capecitabine vs. Lapatinib + Capecitabine, in Subjects with Solid Tumors and ErbB-2 Positive Metastatic or locally advanced Breast Cancer
CTID: null
Phase: Phase 2    Status: Completed
Date: 2008-11-24
A Phase I/II Study of HKI-272 in Combination With Vinorelbine in Subjects With Solid Tumors and Metastatic Breast Cancer.
CTID: null
Phase: Phase 1, Phase 2    Status: Completed
Date: 2008-05-27
A Phase 1 / 2 Study of HKI-272 in combination With Paclitaxel in Subjects With Solid Tumors and Breast Cancer
CTID: null
Phase: Phase 1, Phase 2    Status: Completed
Date: 2007-10-18
Estudio de Fase I/II de HKI-272 en combinación con trastuzumab (Herceptin) en sujetos con cáncer de mama avanzado
CTID: null
Phase: Phase 1, Phase 2    Status: Completed
Date: 2007-06-13
Phase 2 Study of HKI-272 in Subjects with Advanced Breast Cancer
CTID: null
Phase: Phase 2    Status: Completed
Date: 2006-06-06
Estudio de fase 2 de HKI-272 en sujetos con cáncer de pulmón no microcítico avanzado
CTID: null
Phase: Phase 2    Status: Completed
Date: 2006-02-10

Biological Data
  • Neratinib (HKI-272)

    Effect of HKI-272 on cell cycle regulatory proteins. BT474 cells were incubated with HKI-272 for 12–16 h at 37°C. Protein extracts were analyzed by immunoblotting using cyclin D1, p27, or retinoblastoma (Rb)-specific antibodies. Actin antibodies were used as control. Cancer Res. 2004 Jun 1;64(11):3958-65.

  • Neratinib (HKI-272)

    In vivo activity of HKI-272. A, groups of 10 mice were implanted with 2 × 106 3T3/neu cells. Animals were treated with the vehicle or HKI-272 on days 1–10 (p.o.), beginning the day after implantation. B–E, mice were implanted with BT474 tumor fragments (30 mm3; B), 5 × 106 SK-OV-3 cells (C), 5 × 106 A431 cells (D), or MCF-7 tumor fragments (30 mm3; E). Cancer Res. 2004 Jun 1;64(11):3958-65.

  • Neratinib (HKI-272)

    Inhibition of HER-2 phosphorylation in xenografts. BT474 tumor-bearing mice (5 animals/group) were treated with vehicle or a single dose of HKI-272. Tumors from control and treated mice were dissected at various times after compound administration. Cancer Res. 2004 Jun 1;64(11):3958-65.

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