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| ln Vitro |
In 56% (18/32) of breast cancer cell lines with an IC50 less than 1 μM, risovalisib (CYH33) reduces cell growth [2]. T47D and MCF7 cells are significantly arrested in the G1 phase by CYH33 (0.012-1 μM) in a concentration-dependent manner, lasting for 24 hours [2]. T47D and MCF7 cells' phosphorylation of ERK and Akt is concurrently inhibited by CYH33 (4-1000 nM; 1 hour) [2]. MCF7 and MDA-MB-231 cells are not susceptible to apoptosis induction by CYH33 (0.11-1 μM; 24 hours) [2].
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| ln Vivo |
In mice with human breast cancer cell xenografts, risovalisib (CYH33) (2–20 mg/kg; oral; once daily for 21 days) efficiently reduces tumor growth [2]. PI3K signaling is suppressed in nude mice as evidenced by the considerable down-regulation of phosphorylated Akt levels in tumor tissues following a single oral treatment of CYH33 (20 mg/kg) [2]. In T47D xenografts and R26-Pik3caH1047R; MMTV-Cre mice, CYH33 (10 mg/kg; oral; once daily for 18 or 20 days) delayed the recovery of glycemia and increased area under the glycemic curve (AUC) after CYH33 treatment[2].
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| Cell Assay |
Cell cycle analysis [2]
Cell Types: sensitive T47D, MCF7 and resistant MDA-MB-231 Cell Tested Concentrations: 0.012, 0.037, 0.11, 0.33, 1 μM Incubation Duration: 24 hrs (hours) Experimental Results: T47D and MCF7 cell arrest in G1 phase concentration-dependent sexual pattern, accompanied by a decrease in the number of S-phase cells. There was little effect on the cell cycle distribution of drug-resistant MDA-MB-231 cells. Western Blot Analysis[2] Cell Types: Sensitive T47D, MCF7 and Resistant MDA-MB-231 Cell Tested Concentrations: 4, 12, 37, 111, 333, 1000 nM Incubation Duration: 1 hour Experimental Results: Simultaneous inhibition of ERK and Akt phosphorylation It was effective in both T47D and MCF7 cells, while concentrations as high as 1 μM had little effect on phosphorylated ERK (pERK) in MDA-MB-231 cells. |
| Animal Protocol |
Animal/Disease Models: 4-6 weeks old SCID (severe combined immunodeficient) mouse carrying human breast cancer T47D xenografts [2]
Doses: 2, 5, 10, 20 mg/kg Doses: Oral; one time/day for 21 days Experimental Results: In demonstrated marginal inhibition of tumor growth at lower doses (2 and 5 mg/kg) and Dramatically attenuated tumor growth at doses of 10 or 20 mg/kg, yielding T/C values of 58.36% and 49.42%, respectively. . |
| References |
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| Additional Infomation |
Risovalisib is an orally bioavailable selective inhibitor of the class I phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) catalytic subunit alpha (PIK3CA), with potential antineoplastic activity. Upon administration, risovalisib selectively targets, binds to and inhibits wild-type PIK3CA and its mutated forms, in the PI3K/Akt (protein kinase B) /mammalian target of rapamycin (mTOR) pathway. This results in both apoptosis and growth inhibition in PIK3CA-expressing tumor cells. By specifically targeting PIK3CA, this agent may be more efficacious and less toxic than pan-PI3K inhibitors. Dysregulation of the PI3K/Akt/mTOR pathway is often found in solid tumors and results in the promotion of tumor cell growth, survival, and resistance to chemo- and radio-therapy. PIK3CA, one of the most frequently mutated oncogenes, encodes the p110-alpha catalytic subunit of the class I PI3K.
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| Molecular Formula |
C24H29F3N8O5S
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|---|---|
| Molecular Weight |
598.597873449326
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| Exact Mass |
598.193
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| CAS # |
1494684-28-4
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| Related CAS # |
CYH33 methanesulfonate;1494684-33-1
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| PubChem CID |
72550012
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| Appearance |
White to off-white solid powder
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| LogP |
0.8
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
14
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
41
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| Complexity |
1010
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S(C)(N1CCN(CC2=CN3C(C(=NC(C4C=NC(=CC=4C(F)(F)F)NC(=O)OC)=N3)N3CCOCC3)=C2)CC1)(=O)=O
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| InChi Key |
KTLQDDGRBDLKMN-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C24H29F3N8O5S/c1-39-23(36)29-20-12-18(24(25,26)27)17(13-28-20)21-30-22(33-7-9-40-10-8-33)19-11-16(15-35(19)31-21)14-32-3-5-34(6-4-32)41(2,37)38/h11-13,15H,3-10,14H2,1-2H3,(H,28,29,36)
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| Chemical Name |
methyl N-[5-[6-[(4-methylsulfonylpiperazin-1-yl)methyl]-4-morpholin-4-ylpyrrolo[2,1-f][1,2,4]triazin-2-yl]-4-(trifluoromethyl)pyridin-2-yl]carbamate
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| Synonyms |
CYH-33; CYH33
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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 : ~50 mg/mL (~83.53 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 | 1.6706 mL | 8.3528 mL | 16.7056 mL | |
| 5 mM | 0.3341 mL | 1.6706 mL | 3.3411 mL | |
| 10 mM | 0.1671 mL | 0.8353 mL | 1.6706 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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