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5mg |
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10mg |
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25mg |
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50mg |
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100mg |
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250mg |
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500mg |
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Purity: ≥98%
Theliatinib (formerly HMPL-309; HMPL309; HMPL 309; xiliertinibum; xiliertinib) is a novel and highly potent EGFR-TKI (epidermal growth factor receptor-tyrosine kinase inhibitor) with potential antitumor and anti-angiogenesis activities. It inhibits EGFR with IC50 values of 3 nM and 22 nM against EGFR and EGFR T790M/L858R mutant, and a Ki value of 0.05 nM against EGFR of the wild typ
Targets |
EGFR (IC50 = 3 nM); EGFR (Ki = 0.05 nM); EGFR (L858R/T790M) (IC50 = 22 nM)
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ln Vitro |
Theliatinib exhibits dose-dependent anti-tumor activity in a panel of PDECX (patient-derived esophageal cancer xenograft) models with an overall strong correlation between EGFR H score and tumor growth inhibition. Additionally, the anti-tumor activity of EGFR TKIs, particularly theliatinib, is reduced by aberrant activation or gene mutations of other targets, including PI3K and FGFR[1].
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ln Vivo |
At the conclusion of the trial, theliatinib (2–15 mg/kg; PO; daily; for 21 days; NOD-SCID mice; PDECX 1T0950 model) treatment showed 75% tumor shrinkage with a dosage response [1].
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Cell Assay |
One overnight incubation at 37°C and 5% CO2 is followed by the seeding of duplicate A431 cells (1 × 104 cells/well) in exponential phase in DMEM containing 10% FBS. Following that, 10 μL of test compounds (erlotinib, gefitinib, and theliatinib) at tested concentrations (10~0.005 μM, threefold gradient dilution) are added to each well, with 0.5% DMSO as the final concentration. Add 10 μL/well CCK-8 solution and incubate the cells for an additional hour after 48 hours. We measure the optical density at 450 nm to determine cell survival.
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Animal Protocol |
Animal/Disease Models: NOD-SCID (severe combined immunodeficient) mouse injected with esophageal cancer cells (PDECX 1T0950 model) [1]
Doses: 2 mg/kg, 5 mg/kg, 15 mg/kg Route of Administration: po (po (oral gavage)) daily; one time/day; Results lasting 21 days: Tumor growth was attenuated in a dose-dependent manner in the PDECX 1T0950 model. |
References |
[1]. Ren Y, et al. Anti-tumor efficacy of theliatinib in esophageal cancer patient-derived xenografts models with epidermal growth factor receptor (EGFR) overexpression and gene amplification. Oncotarget. 2017 Apr 19;8(31):50832-50844.
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Molecular Formula |
C25H26N6O2
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Molecular Weight |
442.512944698334
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Exact Mass |
442.21
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Elemental Analysis |
C, 67.86; H, 5.92; N, 18.99; O, 7.23
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CAS # |
1353644-70-8
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Related CAS # |
Theliatinib tartrate;2413487-72-4
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Appearance |
Solid powder
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SMILES |
CN1CC[C@H]2[C@@H]1CN(C2)C(=O)NC3=C(C=C4C(=C3)C(=NC=N4)NC5=CC=CC(=C5)C#C)OC
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InChi Key |
FSXCKIBROURMFT-VGSWGCGISA-N
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InChi Code |
InChI=1S/C25H26N6O2/c1-4-16-6-5-7-18(10-16)28-24-19-11-21(23(33-3)12-20(19)26-15-27-24)29-25(32)31-13-17-8-9-30(2)22(17)14-31/h1,5-7,10-12,15,17,22H,8-9,13-14H2,2-3H3,(H,29,32)(H,26,27,28)/t17-,22+/m1/s1
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Chemical Name |
(3aR,6aR)-N-[4-(3-ethynylanilino)-7-methoxyquinazolin-6-yl]-1-methyl-2,3,3a,4,6,6a-hexahydropyrrolo[2,3-c]pyrrole-5-carboxamide
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Synonyms |
Theliatinib; HMPL309; HMPL 309; HMP-L309; xiliertinibum; xiliertinib
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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: 1~5 mg/mL (2.3~11.3 mM)
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Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80: Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 :Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400  (Please use freshly prepared in vivo formulations for optimal results.) |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 2.2598 mL | 11.2992 mL | 22.5984 mL | |
5 mM | 0.4520 mL | 2.2598 mL | 4.5197 mL | |
10 mM | 0.2260 mL | 1.1299 mL | 2.2598 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.
NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
NCT02601248 | Completed | Drug: Theliatinib | Cancer | Hutchison Medipharma Limited | October 2012 | Phase 1 |
NCT02601274 | Terminated | Drug: Theliatinib | Cancer | Hutchison Medipharma Limited | April 2015 | Phase 1 |
Chemical structure of theliatinib and its enzyme kinetics on EGFR inhibition. Oncotarget. 2017 Aug 1; 8(31): 50832–50844. td> |
Anti-tumor efficacy of theliatinib in PDECX models with EGFR gene amplification and overexpression. Oncotarget. 2017 Aug 1; 8(31): 50832–50844. td> |
Anti-tumor efficacy of theliatinib in PDECX models without EGFR gene amplification. Oncotarget. 2017 Aug 1; 8(31): 50832–50844. td> |