| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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Purity: ≥98%
SHP394 is a novel, potent and orally bioavailable SHP2 inhibitor with IC50 of 23 nM. It has high lipophilic efficiency, improved potency, and enhanced pharmacokinetic properties. The overall polarity of SHP394 enabled excellent aqueous solubility (0.98 mM in pH 6.8 buffer), but low permeability (Papp(A-B) 1.02 × 10−6 cm/s), and apparent efflux (B-A/A-B = 15) in Caco-2 cells. The metabolic stability of SHP394 in both rat and mouse liver microsomes indicated low clearance (Clint = 7.9−11.1 μL/min/mg; T1/2 > 2 h) for both species.
| ln Vitro |
SHP394 has an IC50 of 297 nM, which suppresses the growth of Caco-2 cells[1]. In vitro, SHP394 has anti-proliferative action (IC50= 1.38 μM) against the Detroit-562 pharyngeal cancer cell line [1]. In KYSE520 cells, SHP394 lowers p-ERK with an IC50 of 18 nM [1].
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| ln Vivo |
Tumor volume is reduced by SHP394 (20–80 mg/kg; oral gavage; twice daily) in a dose-dependent manner [1]. Within 14 days, SHP394 (80 mg/kg; oral gavage; twice daily) caused a 34% tumor regression and decreased the body weight of the mice [1].
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| Animal Protocol |
Animal/Disease Models: Sixweeks old female athymic NU/nu (nude) mice were subcutaneously (sc) (sc) inoculated with Detroit-562 pharyngeal cancer cells [1].
Doses: 20, 40 and 80 mg/kg Route of Administration: po (oral gavage); twice (two times) daily Experimental Results: Demonstrated significant dose-dependent reduction in tumor volume. |
| References |
| Molecular Formula |
C20H25F3N6O2S
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|---|---|
| Molecular Weight |
470.511712789536
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| Exact Mass |
470.171
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| CAS # |
2055757-40-7
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| PubChem CID |
124150499
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| Appearance |
White to off-white solid powder
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| LogP |
0.9
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
32
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| Complexity |
812
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| Defined Atom Stereocenter Count |
2
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| SMILES |
S(C1=CC=CN=C1C(F)(F)F)C1=C(N)N=C(N(C)C1=O)N1CCC2(CO[C@@H](C)[C@H]2N)CC1
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| InChi Key |
QZHZIDHAIVAHMD-SMDDNHRTSA-N
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| InChi Code |
InChI=1S/C20H25F3N6O2S/c1-11-14(24)19(10-31-11)5-8-29(9-6-19)18-27-16(25)13(17(30)28(18)2)32-12-4-3-7-26-15(12)20(21,22)23/h3-4,7,11,14H,5-6,8-10,24-25H2,1-2H3/t11-,14+/m0/s1
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| Chemical Name |
6-amino-2-((3S,4S)-4-amino-3-methyl-2-oxa-8-azaspiro[4.5]decan-8-yl)-3-methyl-5-((2-(trifluoromethyl)pyridin-3-yl)thio)pyrimidin-4(3H)-one
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| Synonyms |
SHP394 SHP-394 SHP 394
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| 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 : ~24 mg/mL (~51.01 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 6.25 mg/mL (13.28 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 62.5 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: ≥ 6.25 mg/mL (13.28 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 62.5 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: ≥ 6.25 mg/mL (13.28 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 | 2.1254 mL | 10.6268 mL | 21.2535 mL | |
| 5 mM | 0.4251 mL | 2.1254 mL | 4.2507 mL | |
| 10 mM | 0.2125 mL | 1.0627 mL | 2.1254 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.
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