Sitravatinib (Synonyms: MGCD-516) |
カタログ番号GC19332
One-Click Copy Product Info
|
シトラバチニブ (MGCD516) は、1.5 nM、2 nM、2 nM、5 nM、6 nM、6 nM、8 nM、0.5 nM、29 nM、5 nM、および 9 の IC50 を持つ、経口投与可能な受容体チロシンキナーゼ (RTK) 阻害剤です。 Axl、MER、VEGFR3、VEGFR2、VEGFR1、KIT、FLT3、DDR2、DDR1、TRKA、TRKB はそれぞれ nM です 。
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1123837-84-2
Sample solution is provided at 25 µL, 10mM.
_1-3.$$$39978408@51.jpg');)
_1-9.$$$38538795@65.jpg');)
_1-9.$$$39112701@51.jpg');)
_1-7.$$$37316672@70.jpg');)
_366-372.$$$36198801@70.jpg');)
.$$$38565142@65.jpg');)
_1867-1883.$$$33248023@67.jpg');)
_eads6055.$$$39977546@45.jpg');)
_eadm9805.$$$40080571@45.jpg');)
_eadj3020.$$$39666821@45.jpg');)
_1-20.$$$39757301@28.jpg');)
_1-24.$$$38898113@28.jpg');)
_273-287.$$$36806353@46.jpg');)
_1-16.$$$37156877@44.jpg');)
_1-19.$$$37460805@44.jpg');)
_1291-1307.$$$34518654@46.jpg');)
Sitravatinib is a tyrosine kinase inhibitor (TKI) that targets the TYRO3, AXL, and MERTK (TAM) receptors, the vascular endothelial growth factor receptor (VEGFR) family, c-Kit, and c-MET[1,2].
In vitro，Sitravatinib treatment decreased MET, EphA2, EphA3, or AXL protein phosphorylation levels in sunitinib and axitinib-resistant (SuR/AxR) human LM2-4 and mouse RENCA or 4T1 cells after 3 hours, enhanced effect in resistant cell lines[2]. The IC50 values for the three sensitive cell lines (DDLS, MPNST and LS141) ranged between 250–750nM, IC50 values for the less sensitive cell lines (A673 and Saos2) ranged between 1.5–2.0mM[3].
In vivo, Sitravatinib (2mg/kg; oral; every other day for 14 days) alone had 37% inhibitory effect on tumor volume (IRV) and 28% inhibitory effect on tumor weight (IRW) in the SW620 mice[4]. Sitravatinib (p.o.; 20mg/kg; once per day for 24 days) significantly inhibited tumor progression and induced tumor regression in immunocompetent mice bearing KLN205, CT1B-A5, or E0771 tumors[5].
References:
[1] Msaouel, Pavlos, et al. "Sitravatinib in combination with nivolumab plus ipilimumab in patients with advanced clear cell renal cell carcinoma: a phase 1 trial." Nature communications 16.1 (2025): 578.
[2] Dolan, Melissa, et al. "Enhanced efficacy of sitravatinib in metastatic models of antiangiogenic therapy resistance." PloS one 14.8 (2019): e0220101.
[3] Patwardhan, Parag P., et al. "Significant blockade of multiple receptor tyrosine kinases by MGCD516 (Sitravatinib), a novel small molecule inhibitor, shows potent anti-tumor activity in preclinical models of sarcoma." Oncotarget 7.4 (2015): 4093.
[4] Yang, Yuqi, et al. "Modulating the function of ABCB1: in vitro and in vivo characterization of sitravatinib, a tyrosine kinase inhibitor." Cancer Communications 40.7 (2020): 285-300.
[5] Du, Wenting, et al. "Sitravatinib potentiates immune checkpoint blockade in refractory cancer models." JCI insight 3.21 (2018): e124184.
| Cell experiment [1]: | |
Cell lines | Sunitinib and axitinib-resistant (SuR/AxR) human LM2-4 and mouse RENCA or 4T1 cells |
Preparation Method | 5x103 and 1x103 cells/well (for human and mouse SuR/AxR cell lines, respectively) were plated in 96-well plates in growth media. The next day, growth media was removed and replaced with media containing various concentrations of sitravatinib or cabozantinib. Sitravatinib concentrations ranged between 1 and 10μM for human and 0.02 and 10μM for mouse cell lines, and cabozantinib concentrations ranged between 0.01 and 10μM for mouse cell lines. Preliminary studies were conducted using multiple concentration ranges to arrive at optimal concentrations for IC50 determination. After 72 hours, MTS was added to the cells and, after 2 hours, measured at a wavelength of 490nm using a spectrophotometer. |
Reaction Conditions | 1 and 10μM for human and 0.02 and 10μM for mouse cell lines; 72 hours |
Applications | Sitravatinib drug concentrations needed to reach 50% inhibition (IC50) was consistently less in SuR/AxR cells. |
| Animal experiment [2]: | |
Animal models | SW620 and SW620/Ad300 cells transplanted nude mice |
Preparation Method | SW620 and SW620/Ad300 cells were harvested and washed twice with PBS. Then, both cell lines (1×107 cells in 0.1mL PBS) were injected subcutaneously under armpits of the nude mice. Once the tumor volume reached 500mm3, the mice were euthanized, and the tumor tissues were dissected. Each tumor tissue, except the necrotic part, was cut into 2×2mm in size. The small tumor pieces were implanted subcutaneously under armpits of the nude mice. When the tumor reached approximately 100mm3, the mice were randomly assigned to the following four groups. Sitravatinib was prepared in a final concentration of 0.5% hydroxypropyl methylcellulose (HPMC) and 0.1% Tween-80 solution (pH 1.4) (vehicle A), while vincristine was prepared in autoclaved water (vehicle B). Group 1 mice received vehicle A (administered orally) 1h prior to vehicle B (administered intraperitoneally). Group 2 mice received sitravatinib (prepared in vehicle A, 2mg/kg, administered orally) 1h prior to vehicle B (administered intraperitoneally). Group 3 mice received vehicle A (administered orally) 1h prior to vincristine (prepared in vehicle B, 0.4mg/kg, administered intraperitoneally). Group 4 mice received sitravatinib 1h prior to vincristine at indicated dosages. All treatments were given every other day for 14 days. |
Dosage form | 2mg/kg; oral; every other day for 14 days. |
Applications | Sitravatinib alone had 37% inhibitory effect on tumor volume (IRV) and 28% inhibitory effect on tumor weight (IRW) compared with the control group treated with vehicle only in the SW620 mice. The growth of xenograft tumors was significantly inhibited by combination of sitravatinib and vincristine with 76% IRV and 89% IRW. |
References: | |
| Cas No. | 1123837-84-2 | SDF | |
| 同義語 | MGCD-516 | ||
| Canonical SMILES | O=C(C1(C(NC2=CC=C(F)C=C2)=O)CC1)NC3=CC=C(OC4=C5C(C=C(C6=NC=C(CNCCOC)C=C6)S5)=NC=C4)C(F)=C3 | ||
| Formula | C33H29F2N5O4S | M.Wt | 629.68 |
| 溶解度 | DMSO : ≥ 32 mg/mL (50.82 mM) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 1.5881 mL | 7.9405 mL | 15.8811 mL |
| 5 mM | 317.6 μL | 1.5881 mL | 3.1762 mL |
| 10 mM | 158.8 μL | 794.1 μL | 1.5881 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.50% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 17 reference(s) in Google Scholar.)