| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
IDH1 IDH2
|
|---|---|
| ln Vitro |
With an IC50 of 1.28 nM, mutant IDH1-IN-6 (example 2) suppresses the formation of 2-hydroxyglutarate in HT1080 cells, suggesting that mutant IDHl R132C is inhibited in cells. Mutant IDH1-IN-6 had no effect on aKG, a metabolite produced by wild-type IDHl, suggesting that mutant IDH1-IN-6 prefers mutant IDHl to wild-type IDHl in cells[1].
|
| ln Vivo |
In IDHl mutant xenograft mice, treatment with mutant IDH1-IN-6 (Example 2; 0-32 mg/kg; oral gavage; twice daily; for 3 days) inhibits 2-hydroxyglutarate in a dose-dependent manner[1].
|
| Animal Protocol |
Animal/Disease Models: Athymic nude mice (20-22 g) injected with TB08 cells[1]
Doses: 1 mg/kg, 2 mg/kg, 4 mg/kg, 8 mg/kg, 16 mg/kg, 32 mg/kg Route of Administration: Oral gavage; twice (two times) daily; for 3 days Experimental Results: Inhibitied of 2-hydroxyglutarate in IDHl mutant xenograft mice. |
| References | |
| Additional Infomation |
Crelosidenib is an orally available inhibitor of mutant form of the isocitrate dehydrogenase type 1 (IDH1; IDH-1; IDH1 [NADP+] soluble), including the substitution mutation at arginine (R) in position 132, IDH1(R132), with potential antineoplastic activity. Upon oral administration, crelosidenib specifically and covalently binds to and modifies a single cysteine (Cys269) in the allosteric binding pocket of mutant forms of IDH1, thereby inactivating IDH1. This inhibits the formation of the oncometabolite 2-hydroxyglutarate (2HG) from alpha-ketoglutarate (a-KG). This depletes 2-HG levels, prevents 2HG-mediated signaling and leads to both an induction of cellular differentiation and an inhibition of cellular proliferation in tumor cells expressing mutant forms of IDH1. In addition, crelosidenib has the ability to cross the blood-brain barrier (BBB). IDH1 mutations, including IDH1(R132) mutations, are highly expressed in certain malignancies, including gliomas; they initiate and drive cancer growth by both blocking cell differentiation and catalyzing the formation of 2HG.
|
| Molecular Formula |
C28H36N6O3
|
|---|---|
| Molecular Weight |
504.623846054077
|
| Exact Mass |
504.284
|
| CAS # |
2230263-60-0
|
| PubChem CID |
135125140
|
| Appearance |
Typically exists as solid at room temperature
|
| LogP |
3.7
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
7
|
| Rotatable Bond Count |
9
|
| Heavy Atom Count |
37
|
| Complexity |
806
|
| Defined Atom Stereocenter Count |
2
|
| SMILES |
CCN1C2=NC(=NC=C2COC1=O)N[C@@H](C)C3=CC=C(C=C3)[C@H](CC4CC4)N5CCN(CC5)C(=O)C=C
|
| InChi Key |
AFGYODUJVVOZAX-CYFREDJKSA-N
|
| InChi Code |
InChI=1S/C28H36N6O3/c1-4-25(35)33-14-12-32(13-15-33)24(16-20-6-7-20)22-10-8-21(9-11-22)19(3)30-27-29-17-23-18-37-28(36)34(5-2)26(23)31-27/h4,8-11,17,19-20,24H,1,5-7,12-16,18H2,2-3H3,(H,29,30,31)/t19-,24-/m0/s1
|
| Chemical Name |
7-[[(1S)-1-[4-[(1S)-2-cyclopropyl-1-(4-prop-2-enoylpiperazin-1-yl)ethyl]phenyl]ethyl]amino]-1-ethyl-4H-pyrimido[4,5-d][1,3]oxazin-2-one
|
| 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.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9817 mL | 9.9084 mL | 19.8169 mL | |
| 5 mM | 0.3963 mL | 1.9817 mL | 3.9634 mL | |
| 10 mM | 0.1982 mL | 0.9908 mL | 1.9817 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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