| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
EGFR (WT) 18 nM (IC50) EGFRL858R 0.7 nM (IC50) EGFRL861Q 4 nM (IC50) EGFRL858R/T790M 0.1 nM (IC50) EGFRd746-750 1.4 nM (IC50) EGFRd746-750/T790M 0.89 nM (IC50)
|
|---|---|
| ln Vitro |
With IC50 values of 3.93, 9.39, and 7.63 nM, respectively, oritinib (SH-1028) mesylate (72 hours; 10 μmol/L and the 3-fold dilution; nine times) selectively inhibits EGFR-mutated NCI-H1975, H3255, and PC-9 cells. This inhibition is more sensitive than that of wild-type EGFR in A431 cells[1].
|
| ln Vivo |
Oritinib (SH-1028) mesylate (po; once daily for 14 consecutive days; 2.5–15 mg/kg) suppresses the progression of EGFR-mutant tumors in vivo, but not that of wild-type EGFR[1]. Oritinib (SH-1028) (po; once daily for consecutive 14 days; 2.5–15 mg/kg) mesylate only causes a profound and long-lasting tumor shrinkage in both NCI-H1975 and PC-9 xenograft models with EGFR mutations[1], but only a moderate inhibition of tumor growth in A431 (wild-type EGFR) tumor xenografts. With a Tmax of 1.5–2 hours, oritinib (SH-1028) mesylate (po; once daily for 14 days straight at 2.5–15 mg/kg) exhibits good bioavailability and is widely distributed from the plasma to the tissues. The AUC0–t values of SH-1028 in plasma are 118, 300, and 931 ng × h/ml on Day 1, and 272, 308, and 993 ng × h/ml on Day 14[1].
|
| Cell Assay |
Cell Proliferation Assay[1]
Cell Types: A431 (EGFRWT), H3255 (EGFRL858R), PC-9 (EGFRd746-750) and NCI-H1975 (EGFRL858R/T790M) cells Tested Concentrations: 0.001, 0.01, 0.1, 1, and 10 μM Incubation Duration: 72 hrs (hours) Experimental Results: Selectively inhibited EGFR-mutated NCI-H1975, H3255 and PC-9 cells, with IC50s of 3.93 ±1.12, 9.39±0.88 and 7.63±0.18 nmol/L, respectively, which were about 198-, 83- and 102-fold more sensitive than the inhibition of wild-type EGFR in A431 cells (IC50=778.89±134.74 nM). |
| Animal Protocol |
Animal/Disease Models: Nu/Nu female nude mice (6-8 weeks) bearing human lung cancer cell lines[1]
Doses: 2.5, 5, and 15 mg/kg (SH-1028) and control group ( osimertinib, 5 mg/kg) Route of Administration: po; one time/day for consecutive 14 days Experimental Results: Only induced a moderate tumor growth inhibition in A431 (wild-type EGFR) tumor xenografts, while caused profound and sustained tumor shrinkage in both NCI-H1975 and PC-9 xenograft models with EGFR mutations with 5 mg/kg/day. |
| References |
| Molecular Formula |
C32H41N7O5S
|
|---|---|
| Exact Mass |
635.288
|
| CAS # |
2180164-79-6
|
| Related CAS # |
Oritinib;2035089-28-0
|
| PubChem CID |
163323601
|
| Appearance |
Typically exists as solid at room temperature
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
10
|
| Rotatable Bond Count |
10
|
| Heavy Atom Count |
45
|
| Complexity |
935
|
| Defined Atom Stereocenter Count |
0
|
| InChi Key |
IKCINODAIQYCSW-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C31H37N7O2.CH4O3S/c1-6-29(39)33-23-19-24(28(40-5)20-27(23)37(4)18-17-36(2)3)35-31-32-15-14-22(34-31)30-21-11-7-8-12-25(21)38-16-10-9-13-26(30)38;1-5(2,3)4/h6-8,11-12,14-15,19-20H,1,9-10,13,16-18H2,2-5H3,(H,33,39)(H,32,34,35);1H3,(H,2,3,4)
|
| Chemical Name |
N-[2-[2-(dimethylamino)ethyl-methylamino]-4-methoxy-5-[[4-(6,7,8,9-tetrahydropyrido[1,2-a]indol-10-yl)pyrimidin-2-yl]amino]phenyl]prop-2-enamide;methanesulfonic acid
|
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| 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.) |
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.
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