| Size | Price | |
|---|---|---|
| 100mg | ||
| 500mg | ||
| Other Sizes |
| ln Vitro |
In a cell-free experiment for Aβ generation utilizing detergent-solubilizized membranes obtained from HeLa cells, the IC50 of Nirogacestat (PF-03084014) for γ-secretase enzyme inhibition is found to be 6.2 nM. In cellular experiments employing HPB-ALL cells mutated in both the heterodimerization and PEST domains of Notch1, the cell IC50 is found to be 13.3 nM when tested for suppression of Notch receptor cleavage. In HPB-ALL and TALL-1 cells, nirogacestat significantly increases caspase-3 activity and, following a 7-day therapy, cleaved PARP and cleaved caspase-3 are induced[1].
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|---|---|
| ln Vivo |
In this model, nirogacestat (PF-03084014), when administered twice daily for 14 days, exhibits strong anticancer activity. The maximum tumor growth inhibition of around 92% is achieved at high dose levels (150 mg/kg). Tumor growth inhibition is dose dependant. Nirogacestat is well tolerated at dose levels below 100 mg/kg in tumor growth inhibition trials when mice receive repetitive twice-daily treatment for longer than a week; no appreciable weight loss, morbidity, or mortality are noted. However, mice exhibit diarrhea and weight loss (10–15%) about 10 days after compound treatment when the dose is increased to 150 mg/kg. If dose holidays are taken, the body weight of treated animals typically recovers to normal, indicating that Nirogacestat's toxicity is reversible[1].
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| References | |
| Additional Infomation |
Nirogacestat dihydrobromide is a hydrobromide salt obtained by reaction of nirogacestat with two equivalents of hydrobromic acid. It has a role as an antineoplastic agent and a gamma-secretase modulator. It contains a nirogacestat(2+).
Nirogacestat Hydrobromide is the hydrobromide salt form of nirogacestat, a selective gamma secretase (GS) inhibitor with antitumor activity. Upon administration, nirogacestat targets and binds to GS, thereby blocking the proteolytic activation of Notch receptors. This inhibits the Notch signaling pathway and results in the induction of apoptosis in tumor cells that overexpress Notch. The integral membrane protein GS is a multi-subunit protease complex that cleaves single-pass transmembrane proteins, such as Notch receptors, at residues within their transmembrane domains. Overexpression of the Notch signaling pathway has been correlated with increased tumor cell growth and survival. Drug Indication Treatment of soft tissue sarcoma |
| Molecular Formula |
C27H43BR2F2N5O
|
|---|---|
| Molecular Weight |
651.47
|
| Exact Mass |
649.18
|
| CAS # |
1962925-29-6
|
| Related CAS # |
Nirogacestat;1290543-63-3
|
| PubChem CID |
121513889
|
| Appearance |
White to off-white solid powder
|
| Hydrogen Bond Donor Count |
5
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
11
|
| Heavy Atom Count |
37
|
| Complexity |
685
|
| Defined Atom Stereocenter Count |
2
|
| SMILES |
CCC[C@@H](C(=O)NC1=CN(C=N1)C(C)(C)CNCC(C)(C)C)N[C@H]2CCC3=C(C2)C(=CC(=C3)F)F.Br.Br
|
| InChi Key |
LXEYYZYDWLAIPW-KBVFCZPLSA-N
|
| InChi Code |
InChI=1S/C27H41F2N5O.2BrH/c1-7-8-23(32-20-10-9-18-11-19(28)12-22(29)21(18)13-20)25(35)33-24-14-34(17-31-24)27(5,6)16-30-15-26(2,3)4;;/h11-12,14,17,20,23,30,32H,7-10,13,15-16H2,1-6H3,(H,33,35);2*1H/t20-,23-;;/m0../s1
|
| Chemical Name |
(2S)-2-[[(2S)-6,8-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl]amino]-N-[1-[1-(2,2-dimethylpropylamino)-2-methylpropan-2-yl]imidazol-4-yl]pentanamide;dihydrobromide
|
| Synonyms |
Ogsiveo
|
| 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
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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 | 1.5350 mL | 7.6750 mL | 15.3499 mL | |
| 5 mM | 0.3070 mL | 1.5350 mL | 3.0700 mL | |
| 10 mM | 0.1535 mL | 0.7675 mL | 1.5350 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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