| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| 500mg |
|
||
| Other Sizes |
|
Purity: ≥98%
Sonidegib phosphate or Sonidegib diphosphate, the diphosphate salt of sonidegib (also known as NVP-LDE225, Erismodegib, Sonidegib; trade name of Odomzo) is a potent and orally bioavailable small-molecule antagonist of the Smoothened (Smo) with potential anticancer activity. It inhibits the Hedgehog (Hh) signaling with IC50 of 1.3 nM (mouse) and 2.5 nM (human) in cell-free assays, respectively. LDE225 (NVP-LDE225, Erismodegib, Sonidegib) specifically binds to the Hedgehog (Hh)-ligand cell surface receptor Smo, resulting in the suppression of the Hedgehog signaling pathway and thus the inhibition of tumor cell growth in which the Hedgehog pathway is abnormally activated. It is an anticancer drug that received FDA approval in 2015 for the treatment of basal cell carcinoma.
| ln Vitro |
Sonidegib (NVP-LDE225) has an IC50 value of more than 10 μM for the main human CYP450 drug-metabolizing enzymes[1]. When administered alone or in conjunction with nilotinib, sonidegib (LDE225), a small molecule SMO inhibitor under clinical investigation, inhibits the Hh pathway in CD34+ chronic phase (CP)-chronic myeloid leukemia (CML) cells, thereby decreasing the quantity and potential for self-renewal of CML leukaemia stem cells (LSC). Similar to cyclopamine, sonidegib directly interacts with SMO to decrease the expression of downstream Hh signaling targets. Serum-free medium (SFM)±Sonidegib is used to cultivate primary CD34+ CP-CML cells during 6, 24, and 72 hours (h). After being exposed to Sonidegib at 10 nM; 0.78-fold and 100 nM; 0.73-fold, respectively (p<0.01), GLI1 is considerably downregulated at 72 hours, however there is diversity throughout the biological samples[2].
|
||
|---|---|---|---|
| ln Vivo |
Sonidegib (NVP-LDE225) has a pKa of 4.2, making it a weak base with comparatively low solubility in water. Sonidegib dose-related antitumor activity in the subcutaneous Ptch+/-p53-/- medulloblastoma allograft mouse model was observed 10 days after oral administration of a suspension of the diphosphate salt. Sonidegib exhibits a significant tumor growth inhibition at a dose of 5 mg/kg/day qd, with a corresponding T/C value of 33% (p<0.05) in comparison to vehicle controls. Sonidegib provides 51 and 83% regression when administered at doses of 10 and 20 mg/kg/day qd, respectively[1]. Secondary recipient mice are transplanted with bone marrow and spleen cells from a subset of treated mice. Comparing bone marrow (BM) or spleen cells transplanted from mice treated with Sonidegib (LDE225)+Nilotinib to Sonidegib or Nilotinib alone, the latter reduces the development of leukemia in secondary recipients and lowers the white cell count (WCC)[2].
|
||
| Animal Protocol |
|
||
| References |
[1]. Pan S, et al. Discovery of NVP-LDE225, a Potent and Selective Smoothened Antagonist. ACS Med Chem Lett. 2010 Mar 16;1(3):130-4.
[2]. Irvine DA, et al. Deregulated hedgehog pathway signaling is inhibited by the smoothened antagonist LDE225 (Sonidegib) in chronic phase chronic myeloid leukaemia. Sci Rep. 2016 May 9;6:25476 |
| Molecular Formula |
C26H32F3N3O11P2
|
|---|---|
| Molecular Weight |
681.49
|
| CAS # |
1218778-77-8
|
| Related CAS # |
Sonidegib;956697-53-3
|
| SMILES |
N1(C[C@H](C)O[C@H](C)C1)C1=CC=C(C=N1)NC(=O)C1C=CC=C(C2C=CC(=CC=2)OC(F)(F)F)C=1C.P(O)(O)(O)=O.P(O)(O)(O)=O
|
| Synonyms |
Sonidegib phosphate; Sonidegib diphosphate; LDE 225 phosphate; LDE 225 diphosphate;LDE-225 phosphate; LDE225 phosphate; LDE-225 diphosphate; LDE225 diphosphate; NVP-LDE225 diphosphate; NVP LDE-225 diphosphate; NVP-LDE225 phosphate; NVP LDE-225 phosphate; NVP LDE225 phosphate; Erismodegib phosphate; Erismodegib diphosphate; trade name of Odomzo
|
| 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) |
|
|||
|---|---|---|---|---|
| Solubility (In Vivo) |
|
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.4674 mL | 7.3369 mL | 14.6737 mL | |
| 5 mM | 0.2935 mL | 1.4674 mL | 2.9347 mL | |
| 10 mM | 0.1467 mL | 0.7337 mL | 1.4674 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 |
| NCT02254551 | Terminated Has Results | Drug: LDE225 Drug: Bortezomib |
Multiple Myeloma | SCRI Development Innovations, LLC | January 2015 | Phase 2 |
| NCT04066504 | Active, not recruiting | Drug: sonidegib | Basal Cell Carcinoma | Sun Pharmaceutical Industries Limited | March 11, 2019 | |
| NCT02086513 | Terminated | Drug: LDE225 | Graft Versus Host Disease | Massachusetts General Hospital | April 2014 | Phase 1 |
| NCT04007744 | Recruiting | Biological: Pembrolizumab Drug: Sonidegib |
Clinical Stage III Cutaneous Melanoma AJCC v8 Clinical Stage III Gastric Cancer AJCC v8 |
Mayo Clinic | February 13, 2020 | Phase 1 |
 Antitumor activity in an orthotopic Ptch+/−p53−/−medulloblastoma allograft model in nude mice upon treatment with5mdiphosphate salt dosed at 40 mg/kg/day po bid or vehicle at equal dose volume.ACS Med Chem Lett. 2010 Jun 10; 1(3): 130–134. |
|---|
 Antitumor activity upon treatment with5mdiphosphate salt or vehicle in a Ptch+/−p53−/− medulloblastoma subcutaneous allograft model in nude mice.ACS Med Chem Lett. 2010 Jun 10; 1(3): 130–134. |
 Gli1 mRNA inhibition (open circle), tumor PK (filled squares), and plasma PK (filled triangles) in Ptch+/−p53−/−medulloblastoma model after treatment with5m (Sonidegib, or erismodegib, LDE225, NVP-LDE225).ACS Med Chem Lett. 2010 Jun 10; 1(3): 130–134. |
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA