| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
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| ln Vitro |
Treatment with siropilenastat (DRP-104) exhibits extensive effects on immune cell modulation, such as enhanced T, NK, and macrophages. Pro-tumorigenic cytokines including VEGF and KC (IL-8) are reduced by sirpiglenastat[1].
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|---|---|
| ln Vivo |
At day 12, 90% tumor growth inhibition is seen in CT26 bearing mice treated with Sirpiglenastat (DRP-104) (0.5 mg/kg; sc; once daily; for five days). 36 days are the median survival time[1]. In the H22 model, therapy with sirpiglenastat (0.5 mg/kg; sc) effectively suppresses tumor growth[1].
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| Animal Protocol |
Animal/Disease Models: CT26 bearing mice[1]
Doses: 0.5 mg/kg Route of Administration: sc; one time/day; for 5 days Experimental Results: demonstrated tumor growth inhibition in mice. |
| References |
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| Additional Infomation |
Sirpiglenastat, also known as DRP-104, is a prodrug of [6-diazo-5-oxo-L-norleucine] (DON), which is a broad-acting glutamine antagonist. It is under investigation in clinical trial NCT04471415 (Study to Investigate DRP-104 in Adults With Advanced Solid Tumors).
Sirpiglenastat is a broad acting glutamine antagonist, with potential immunomodulatory and antineoplastic activities. Upon administration, DON (6-Diazo-5-oxo-L-norleucine), the active moiety of sirpiglenastat, irreversibly inhibits multiple enzymes involved in glutamine metabolism. Blocking glutamine metabolism inhibits proliferation in rapidly growing tumor cells and leads to an induction of cell death. Unlike normal healthy cells, glutamine-dependent tumors rely heavily on the intracellular conversion of exogenous glutamine into glutamate and glutamate metabolites to both provide energy and generate building blocks for the production of macromolecules, which are needed for cellular growth and survival. In addition, blocking glutamine metabolism leads to the accumulation of glutamine in tumor cells and increases glutamine concentration in the tumor microenvironment (TME) upon tumor cell death. As glutamine is essential for T-cell generation, DON may also enhance T-cell proliferation and activation in the TME, which may lead to further killing of tumor cells. The conversion of sirpiglenastat to the active moiety DON occurs primarily in tumor cells, allowing glutamine metabolism in healthy cells which may lessen adverse effects. |
| Molecular Formula |
C22H27N5O5
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|---|---|
| Molecular Weight |
441.480284929276
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| Exact Mass |
441.201
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| CAS # |
2079939-05-0
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| PubChem CID |
137308771
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| Appearance |
Off-white to yellow solid powder
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| LogP |
1.2
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
12
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| Heavy Atom Count |
32
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| Complexity |
749
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| Defined Atom Stereocenter Count |
2
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| SMILES |
C(C1=CNC2=CC=CC=C12)[C@H](NC(=O)C)C(=O)N[C@@H](CCC(=O)C=[N+]=[N-])C(=O)OC(C)C
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| InChi Key |
LQNMCWOJACNQQM-PMACEKPBSA-N
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| InChi Code |
InChI=1S/C22H27N5O5/c1-13(2)32-22(31)19(9-8-16(29)12-25-23)27-21(30)20(26-14(3)28)10-15-11-24-18-7-5-4-6-17(15)18/h4-7,11-13,19-20,24H,8-10H2,1-3H3,(H,26,28)(H,27,30)/t19-,20-/m0/s1
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| Chemical Name |
propan-2-yl (2S)-2-[[(2S)-2-acetamido-3-(1H-indol-3-yl)propanoyl]amino]-6-diazo-5-oxohexanoate
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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 and light. |
| 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 (226.51 mM)
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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 | 2.2651 mL | 11.3255 mL | 22.6511 mL | |
| 5 mM | 0.4530 mL | 2.2651 mL | 4.5302 mL | |
| 10 mM | 0.2265 mL | 1.1326 mL | 2.2651 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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