| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Targets |
EGFRL858R/T790M 48 nM (IC50) EGFRWT 15 nM (IC50)
DBPR112 targets the epidermal growth factor receptor (EGFR). It is an orally active furanopyrimidine-based inhibitor that targets both wild-type EGFR and the L858R/T790M mutant. By occupying the ATP-binding site, it inhibits EGFR kinase activity, blocking downstream signaling pathways that promote tumor cell proliferation and survival. Its activity against the T790M mutant is relevant for overcoming resistance. |
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| ln Vitro |
In a dose-dependent manner, DBPR112 (compound 78; 0.32-1000 nM; 16 hours) reduces phosphorylated EGFR[1]. HCC827 (CC50=25 nM), H1975 (CC50=620 nM), and A431 Cell (CC50=1.02 μM) cell lines are all inhibited by DBPR112[1]. With its occupation of the ATP-binding site and its interactions—covalent, hydrogen, and hydrophobic—with neighboring residues, DBPR112 exhibits a strong inhibitory effect on WT EGFR[1].
In vitro, DBPR112 has been shown to be a potent inhibitor of EGFR with IC50 values of 15 nM for EGFRWT and 48 nM for EGFRL858R/T790M. Its activity is assessed using biochemical kinase assays that measure the phosphorylation of a substrate in the presence of the compound. These studies confirm its potential as a therapeutic agent. |
| ln Vivo |
In the HCC827 tumor model, DBPR112 (orally administered at 20–50 mg/kg, five days per week for two weeks in a row) dramatically slows tumor growth. In the H1975 tumor model, DBPR112 (orally; 50 mg/kg; once daily for 15 days) significantly inhibits tumor development (mean tumor growth suppression of 34%)[1]. The T1/2, CL, and Vss of DBPR112 (IV; 5 mg/kg) in rats are 2.3 hours, 55.6 mL/min·kg, and 8.6 L/kg, respectively[1].
In vivo, DBPR112 has demonstrated significant antitumor efficacy. Its oral bioavailability and potent activity against EGFR support its evaluation in animal models of EGFR-driven cancers. These studies provide evidence for its therapeutic potential. |
| Enzyme Assay |
Cell-free assays for DBPR112 typically involve measuring its inhibitory activity against wild-type and mutant EGFR kinases using biochemical kinase assays. The IC50 values of 15 nM and 48 nM for EGFRWT and EGFRL858R/T790M, respectively, are determined by measuring the phosphorylation of a substrate in the presence of varying concentrations of the inhibitor.
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: H1975 cells Tested Concentrations: 0.32, 1.6, 8.0, 40, 200, 1000 nM Incubation Duration: 16 hrs (hours) Experimental Results: Induced reduction of phosphorylated EGFR in a dose-dependent manner in H1975 cells. In vitro cellular assays are conducted to evaluate the functional activity of DBPR112. Cancer cell lines harboring EGFR mutations are treated with the compound. Cell viability and proliferation are measured to assess the compound's anti-proliferative effects. EGFR phosphorylation is also measured to confirm inhibition of the target kinase. |
| Animal Protocol |
Animal/Disease Models: HCC827 tumor model (6- to 8weeks old athymic NU-Fox1nu nude mice)[1]
Doses: 20, 50 mg/kg Route of Administration: po (oral gavage) 5 days/week for 2 consecutive weeks (days 1-5 and 8-12) Experimental Results: Dramatically decreased tumor growth. Animal/Disease Models: Rats[1] Doses: 5 mg/kg for IV and 20 mg/kg for PO (pharmacokinetic/PK Analysis) Route of Administration: IV or PO Experimental Results: Had a T1/2 of 2.3 hrs (hours), a CL of 55.6 mL/min·kg, and a Vss of 8.6 L/kg by IV. Had a T1/2 of 3.4 hrs (hours), a Cmax of 508 ng/mL and an AUC of 2978 ng/mL·h by PO. In vivo animal experiments typically involve xenograft models of EGFR-driven cancers. Mice bearing these tumors are administered DBPR112 orally. Tumor growth is monitored over time to assess the compound's efficacy. These studies are essential for demonstrating the in vivo antitumor activity of the compound. |
| ADME/Pharmacokinetics |
The pharmacokinetic properties of DBPR112 are characteristic of an orally bioavailable small molecule inhibitor. Its CAS number is 1226549-49-0. The compound is designed to have favorable drug-like properties, including good oral bioavailability and metabolic stability, to support efficacy in vivo.
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| Toxicity/Toxicokinetics |
The toxicity profile of DBPR112 is likely consistent with other EGFR inhibitors. Common adverse effects may include diarrhea, skin rash, and fatigue. Its activity against both wild-type and mutant EGFR may result in a safety profile similar to earlier-generation TKIs. Preclinical studies would typically involve acute and chronic dosing in animal models to assess safety margins.
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| References | |
| Additional Infomation |
(E)-4-(dimethylamino)-N-[3-[4-[[(1S)-2-hydroxy-1-phenylethyl]amino]-6-phenylfuro[2,3-d]pyrimidin-5-yl]phenyl]but-2-enamide is a highly bioavailable, orally bioavailable dual kinase inhibitor that inhibits the activity of epidermal growth factor receptor (EGFR; ErbB1) and human epidermal growth factor receptor 2 (HER2; EGFR2; ErbB2), including EGFR L858R, EGFR T790M, and HER2 exon 20 insertion (Ex20ins) mutations, exhibiting potential antitumor activity. After oral administration, gozartinib targets and binds to and inhibits the activity of EGFR or HER2 insertions or mutations. This blocks EGFR/HER2-mediated signaling, thereby inducing EGFR/HER2-overexpressing tumor cell death and inhibiting tumor growth. The ErbB receptor tyrosine kinase family is involved in multiple key cellular functions, including cell growth and survival. Changes in EGFR and HER2 can continuously upregulate kinase activity.
DBPR112 is an orally active EGFR inhibitor that targets both wild-type and T790M mutant EGFR. It has demonstrated significant antitumor efficacy in preclinical studies. The compound is a valuable research tool for studying EGFR-driven malignancies and is being investigated for its potential in treating non-small cell lung cancer and other solid tumors. |
| Molecular Formula |
C32H31N5O3
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|---|---|
| Molecular Weight |
533.6202
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| Exact Mass |
533.242
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| CAS # |
1226549-49-0
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| PubChem CID |
46212971
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
4.9
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
10
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| Heavy Atom Count |
40
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| Complexity |
812
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| Defined Atom Stereocenter Count |
1
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| SMILES |
O1C2C(=C(N=C([H])N=2)N([H])[C@]([H])(C([H])([H])O[H])C2C([H])=C([H])C([H])=C([H])C=2[H])C(C2C([H])=C([H])C([H])=C(C=2[H])N([H])C(/C(/[H])=C(\[H])/C([H])([H])N(C([H])([H])[H])C([H])([H])[H])=O)=C1C1C([H])=C([H])C([H])=C([H])C=1[H]
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| InChi Key |
NQAMTZUVRFRJCZ-VMMYIZNOSA-N
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| InChi Code |
InChI=1S/C32H31N5O3/c1-37(2)18-10-17-27(39)35-25-16-9-15-24(19-25)28-29-31(36-26(20-38)22-11-5-3-6-12-22)33-21-34-32(29)40-30(28)23-13-7-4-8-14-23/h3-17,19,21,26,38H,18,20H2,1-2H3,(H,35,39)(H,33,34,36)/b17-10+/t26-/m1/s1
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| Chemical Name |
(E)-4-(dimethylamino)-N-[3-[4-[[(1S)-2-hydroxy-1-phenylethyl]amino]-6-phenylfuro[2,3-d]pyrimidin-5-yl]phenyl]but-2-enamide
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO: 250 mg/mL (468.50 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.90 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 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 (3.90 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 ultrasonication. 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 (3.90 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 | 1.8740 mL | 9.3700 mL | 18.7399 mL | |
| 5 mM | 0.3748 mL | 1.8740 mL | 3.7480 mL | |
| 10 mM | 0.1874 mL | 0.9370 mL | 1.8740 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.
Link: https://clinicaltrials.gov/ct2/show/NCT05532696
Conditions:Advanced Solid Tumor|Non Small Cell Lung Cancer|HER2 MutationsLink: https://clinicaltrials.gov/ct2/show/NCT03246854
Conditions:Head and Neck Cancer|NSCLCProducts are for research use only; We do not sell to patients
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