| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| Other Sizes |
| Targets |
BDTX-189 is a potent and selective inhibitor of allosteric EGFR and HER2 oncogenic mutations. The compound binds to EGFR with a Kd of 0.2 nM and to HER2 with a Kd of 0.76 nM, demonstrating high potency. It also shows activity against BLK (Kd = 13 nM) and RIPK2 (Kd = 1.2 nM). BDTX-189 is an allosteric inhibitor, meaning it binds to a site distinct from the ATP-binding pocket of the kinase, which may confer advantages in overcoming resistance mutations. By inhibiting EGFR and HER2 signaling, BDTX-189 blocks downstream pathways that drive cancer cell proliferation and survival. The compound has anticancer activity.
|
|---|---|
| ln Vitro |
Tuxobertinib exhibits anti-proliferative action (IC50<100 nM) against the ERBB allosteric oncogene family and is a universal activator of this family of oncogenes [1].
BDTX-189 is a potent and selective inhibitor of allosteric EGFR and HER2 oncogenic mutations with Kd values of 0.2 nM (EGFR), 0.76 nM (HER2), 13 nM (BLK), and 1.2 nM (RIPK2). The compound has anticancer activity. It is an orally available ErbB mutant-specific inhibitor. BDTX-189 inhibits cancer cell proliferation in vitro. The compound's allosteric mechanism of action may provide advantages in overcoming resistance to ATP-competitive inhibitors. |
| ln Vivo |
Tuxobertinib (0-100 mg/kg; sidewall; once daily given 15 days) indicated dose-effect tumor growth suppression and regression in athymic nude mice bearing HER2-labeled S310F Ba/F3 allograft tumors [1 ]. br/> Tuxobertinib (1-50 mg/kg. Facial once daily for 15 days) exhibited model-driven tumor growth inhibition and suppression in athymic nude mice harboring CUTO-14 PDX tumors expressing EGFR mutant EGFR ASV. fade[1].
In vivo, BDTX-189 demonstrates antitumor activity in preclinical models of cancers driven by EGFR and HER2 mutations. As an orally available compound, it can be administered orally for convenient dosing. The compound has shown efficacy in inhibiting tumor growth in xenograft models. BDTX-189 is being evaluated in clinical trials for the treatment of advanced solid tumors with EGFR or HER2 mutations. The MasterKey-01 study (NCT04209465) is a Phase 1/2 trial of BDTX-189 in patients with advanced solid tumors. |
| Enzyme Assay |
Kinase binding assays for BDTX-189 are performed using surface plasmon resonance (SPR) or other biophysical methods. Recombinant EGFR, HER2, BLK, and RIPK2 kinases are immobilized on sensor chips, and varying concentrations of BDTX-189 are flowed over the chips. Binding kinetics (kon, koff) and equilibrium dissociation constants (Kd) are calculated from the sensorgrams. Kinase activity assays measure the inhibition of kinase activity using appropriate peptide substrates and ATP. Selectivity is assessed by screening BDTX-189 against a panel of kinases.
|
| Cell Assay |
Cellular assays for BDTX-189 typically employ cancer cell lines with EGFR or HER2 mutations. Cells are treated with varying concentrations of BDTX-189 for 24-72 hours. Cell viability is assessed using MTT or CellTiter-Glo assays. EGFR and HER2 phosphorylation (p-EGFR, p-HER2) and downstream signaling (p-AKT, p-ERK) are assessed by Western blot. Apoptosis is evaluated by Annexin V/PI staining. Cell cycle analysis is performed by propidium iodide staining. The compound's activity is compared across cell lines with different EGFR/HER2 mutation profiles.
|
| Animal Protocol |
In vivo efficacy is evaluated in mouse xenograft models using human cancer cell lines with EGFR or HER2 mutations. Tumor-bearing mice are treated with BDTX-189 orally at various doses. Tumor volumes are measured every 2-3 days. Pharmacodynamic markers such as EGFR and HER2 phosphorylation are measured in tumor tissues to confirm target engagement. Body weight and clinical signs are monitored for tolerability. The compound's antitumor activity is assessed by tumor growth inhibition.
|
| ADME/Pharmacokinetics |
BDTX-189 is orally available with favorable pharmacokinetic properties. It has molecular formula C29H29ClN6O4 and molecular weight 561.03. The compound is a small molecule with reasonable membrane permeability. It is soluble in DMSO and other organic solvents. For in vivo studies, appropriate oral formulations would be required. Pharmacokinetic studies have characterized absorption, distribution, metabolism, and excretion in preclinical species and humans.
|
| Toxicity/Toxicokinetics |
Preclinical toxicology studies for BDTX-189 are ongoing as part of clinical development. As a kinase inhibitor targeting EGFR and HER2, potential toxicities may include skin rash, diarrhea, and other effects associated with EGFR/HER2 inhibition. The compound has been evaluated in preclinical models with acceptable tolerability. Standard safety pharmacology, genotoxicity, and repeated-dose toxicity studies are being conducted for regulatory approval.
|
| References | |
| Additional Infomation |
Tuxobertinib is a small molecule inhibitor with high oral bioavailability, irreversibility, and selectivity. It inhibits allosteric mutations in certain oncogenic driver genes, including those in the epidermal growth factor receptor (EGFR/ErbB1) and human epidermal growth factor receptor 2 (HER2/neu or ErbB2), such as allosteric mutations in the extracellular domain of HER2 and insertion mutations in exon 20 of EGFR and HER2, exhibiting potential antitumor activity. After oral administration, tuxobertinib selectively binds to and inhibits these allosteric ErbB mutants without affecting wild-type EGFR, thereby selectively inhibiting tumor cell proliferation and angiogenesis in tumors expressing these allosteric ErbB mutations. EGFR and HER2, the ErbB receptor tyrosine kinases, are mutated or overexpressed in many tumor cell types and play a crucial role in tumor cell proliferation and tumor angiogenesis.
BDTX-189 is a potent and selective inhibitor of allosteric EGFR and HER2 oncogenic mutations. It is also known as tuxobertinib. The compound is in Phase 1/2 clinical trials for the treatment of advanced solid tumors (MasterKey-01 study, NCT04209465). BDTX-189 has Kd values of 0.2 nM for EGFR, 0.76 nM for HER2, 13 nM for BLK, and 1.2 nM for RIPK2. It is an orally available ErbB mutant-specific inhibitor. |
| Molecular Formula |
C29H29CLN6O4
|
|---|---|
| Molecular Weight |
561.031365156174
|
| Exact Mass |
560.19
|
| Elemental Analysis |
C, 62.08; H, 5.21; Cl, 6.32; N, 14.98; O, 11.41
|
| CAS # |
2414572-47-5
|
| PubChem CID |
154824631
|
| Appearance |
Off-white to light yellow solid powder
|
| LogP |
3.9
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
9
|
| Rotatable Bond Count |
11
|
| Heavy Atom Count |
40
|
| Complexity |
805
|
| Defined Atom Stereocenter Count |
0
|
| InChi Key |
HIBPKFXWOPYJPZ-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C29H29ClN6O4/c1-2-28(37)35-25-16-22-24(17-27(25)39-14-11-36-9-12-38-13-10-36)32-19-33-29(22)34-20-6-7-26(23(30)15-20)40-18-21-5-3-4-8-31-21/h2-8,15-17,19H,1,9-14,18H2,(H,35,37)(H,32,33,34)
|
| Chemical Name |
N-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]-7-(2-morpholin-4-ylethoxy)quinazolin-6-yl]prop-2-enamide
|
| Synonyms |
BDTX-189; BDTX 189; BDTX189; EGFR/HER2 inhibitor BDTX-189; ErbB mutant-specific inhibitor BDTX-189; tuxobertinib
|
| 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 (In Vitro) |
DMSO : ~41.67 mg/mL (~74.27 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 2.08 mg/mL (3.71 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% 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 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL 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. Solubility in Formulation 2: ≥ 2.08 mg/mL (3.71 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 20.8 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. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (3.71 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7824 mL | 8.9122 mL | 17.8244 mL | |
| 5 mM | 0.3565 mL | 1.7824 mL | 3.5649 mL | |
| 10 mM | 0.1782 mL | 0.8912 mL | 1.7824 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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
