| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| 50mg |
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| Other Sizes |
| Targets |
IDH1
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|---|---|
| ln Vitro |
Safusidenib (DS-1001b) reduces 2-HG levels and hinders the growth of chondrosarcoma cell lines with an IDH1 mutation[1]. While safusidenib has no influence on the proliferation of IDH wild-type cell lines OUMS27 and NDCS-1, it affects the proliferation of IDH1 mutant chondrosarcoma cell lines in a dose-dependent manner (GI50 values for JJ012, L835, OUMS27, and NDCS-1 cells are 81?Day 14 of nM, 77?nM (6 weeks), greater than 10?Day 10 at μM and above 10?μM (day 10) in that order[1]. At the protein level, safusidenib (1 and 10?μM; for 6 weeks) significantly upregulates SOX9, a crucial regulator of chondrocyte differentiation[1]. The protein level of CDKN1C is markedly upregulated by safusidenib (1 μM)[1]. In experiments involving a 2-hour preincubation step, safusidenib (DS-1001b) demonstrates action against IDH1 or IDH2 enzymes with IC50s of 8.4, 11, and 180 nM for IDH1R132H, IDH1R132C, and IDH1WT[2].
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| ln Vivo |
In JJ012 xenografts, sofusidenib (DS-1001b) exhibits antineoplastic action. In xenograft mice, constant feeding of Safusidenib (combined with sterile pellet meal and administered continuously for 6 weeks) inhibits the formation of tumors[1].
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| Cell Assay |
Cell Proliferation Assay[1]
Cell Types: The IDH1 mutant cell lines JJ012 and L835 cells Tested Tested Concentrations: 0.1, 1, and 10 μM Incubation Duration: 0, 3, 6, 9, 12, and 15 days Experimental Results: Impaired proliferation in both cell lines in a dose-dependent manner. Western Blot Analysis[1] Cell Types: L835 cells Tested Tested Concentrations: 0, 1, and 10 μM Incubation Duration: 6 weeks Experimental Results: Markedly upregulated SOX9 at the protein level. |
| Animal Protocol |
Animal/Disease Models: NOD-SCID bearing JJ012 xenograft[3]
Doses: Mixed with sterilized pellet food (CRF-1; Oriental Yeast) and fed ad libitum for 6 weeks. Route of Administration: Fed continuously starting at 3 weeks Experimental Results: Continuous administration Dramatically impaired tumor growth in JJ012 xenograft mice. |
| References |
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| Additional Infomation |
Safusidenib is an oral inhibitor of isocitrate dehydrogenase type 1 (IDH1; IDH-1; IDH1 [NADP+] soluble) mutants, including the arginine-substituted mutant IDH1(R132) (IDH1-R132), which possesses potential antitumor activity. After oral administration, safusidenib specifically binds to and inhibits certain IDH1 mutants, thereby inhibiting the production of the oncogenic metabolite 2-hydroxyglutarate (2HG) from α-ketoglutarate (α-KG). This blocks 2HG-mediated signaling, leading to differentiation induction and proliferation inhibition in tumor cells expressing IDH1 mutations. IDH1(R132) mutants are highly expressed in certain malignancies, including gliomas; they initiate and drive cancer growth by blocking cell differentiation and catalyzing 2HG formation. Safusidenib has minimal targeting and effect on wild-type IDH1, which is expressed in normal healthy cells.
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| Molecular Formula |
C25H18CL3FN2O4
|
|---|---|
| Molecular Weight |
535.778827190399
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| Exact Mass |
534.031
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| CAS # |
1898206-17-1
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| Related CAS # |
DS-1001b;1898207-64-1
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| PubChem CID |
130306983
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| Appearance |
Light yellow to yellow solid
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| LogP |
6.6
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
35
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| Complexity |
834
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=CN(C2=CC=CC(=C12)/C=C/C(=O)O)C(=O)C3=C(ON=C3C4=C(C=C(C=C4Cl)Cl)Cl)C(C)(C)F
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| InChi Key |
BOOMBLZEOHXPPX-BQYQJAHWSA-N
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| InChi Code |
InChI=1S/C25H18Cl3FN2O4/c1-12-11-31(17-6-4-5-13(19(12)17)7-8-18(32)33)24(34)21-22(30-35-23(21)25(2,3)29)20-15(27)9-14(26)10-16(20)28/h4-11H,1-3H3,(H,32,33)/b8-7+
|
| Chemical Name |
(E)-3-[1-[5-(2-fluoropropan-2-yl)-3-(2,4,6-trichlorophenyl)-1,2-oxazole-4-carbonyl]-3-methylindol-4-yl]prop-2-enoic acid
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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 |
| 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: ~100 mg/mL (~186.6 mM; with ultrasonication)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.67 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 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 DMSO stock solution (25.0 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and 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: ≥ 2.5 mg/mL (4.67 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 DMSO stock solution (25.0 mg/mL) to 900 μL of corn oil and mix well. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8664 mL | 9.3322 mL | 18.6644 mL | |
| 5 mM | 0.3733 mL | 1.8664 mL | 3.7329 mL | |
| 10 mM | 0.1866 mL | 0.9332 mL | 1.8664 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.
Link: https://clinicaltrials.gov/ct2/show/NCT04458272
Conditions:WHO Grade II GliomaLink: https://clinicaltrials.gov/ct2/show/NCT05303519
Conditions:Glioma|Astrocytoma, Grade IV|IDH1-mutant Glioma|Astrocytoma, IDH-Mutant, Grade 3|Astrocytoma, IDH-Mutant, Grade 4|Astrocytoma, IDH-Mutant, Grade 2|Oligodendroglioma|Oligodendroglioma, IDH-Mutant and 1p/19q-CodeletedLink: https://clinicaltrials.gov/ct2/show/NCT03030066
Conditions:Glioma
Title:IDH1 Inhibitor AB-218 in Patients With Advanced IDH1 Mutant Cholangiocarcinoma and Other Solid Tumor
Status:Terminated
updateDate:2024-10-18
Ctid:NCT05814536
Link: https://clinicaltrials.gov/ct2/show/NCT05814536
Conditions:Cholangiocarcinoma With IDH1 Mutation|Solid Tumors With IDH1 MutationProducts are for research use only; We do not sell to patients
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