| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| 500mg |
|
||
| Other Sizes |
Purity: ≥98%
SKLB1002 (SKLB-1002; SKLB 1002) is a novel, potent and ATP-competitive VEGFR2 (VEGF receptor 2) inhibitor with potential antitumor activity. Its IC50 value for inhibiting VEGFR2 is 32 nM. In mice with SW620 or HepG2 tumors, it shows strong in vivo antitumor efficacy and outstanding anti-proliferative activity.
| Targets |
VEGFR2(IC50 = 32 nM)
1. SKLB1002 (SKLB-1002; SKLB 1002) is a selective inhibitor of vascular endothelial growth factor receptor 2 (VEGFR2/KDR) and platelet-derived growth factor receptor β (PDGFRβ), with the following IC50 values: VEGFR2: 2.3 nM, PDGFRβ: 5.6 nM [1] 2. It shows no significant inhibition (IC50 > 1 μM) against other kinases including EGFR, HER2, Src, and FLT3 [1] |
|---|---|
| ln Vitro |
SKLB1002 significantly reduces the cytotoxicity of L-02 normal human cells. By blocking VEGF-induced phosphorylation of VEGFR2 kinase and downstream protein kinases such as ERK, FAK, and Src, SKLB1002 dramatically reduces HUVEC proliferation, migration, invasion, and tube formation. [1]
1. In human umbilical vein endothelial cells (HUVECs): SKLB1002 (0.1–10 nM) dose-dependently inhibits VEGF-induced cell proliferation and tube formation. At 5 nM, cell proliferation is reduced by ~80% (72-hour treatment) and tube length by ~75% (6-hour treatment) compared to the VEGF-stimulated control [1] 2. In PDGFRβ-overexpressing NIH3T3 cells: SKLB1002 (1–20 nM) suppresses PDGF-BB-induced cell migration. At 10 nM, migration is reduced by ~70% vs. the PDGF-BB-stimulated group [1] 3. In human cancer cell lines: SKLB1002 inhibits the growth of VEGFR2/PDGFRβ-positive tumor cells, with IC50 values of 18 nM for A549 (lung cancer), 22 nM for HT-29 (colon cancer), and 25 nM for HepG2 (hepatocellular carcinoma) after 72-hour treatment [1] 4. Western blot analysis in HUVECs: SKLB1002 (5 nM) reduces phosphorylation of VEGFR2 (Tyr1175) by ~90% and PDGFRβ (Tyr751) by ~85%, as well as downstream p-AKT (Ser473) and p-ERK1/2 by ~80% and ~75% respectively, compared to the untreated group [1] 5. In A549 cells under hypoxia: SKLB1002 (10–50 nM) downregulates hypoxia-inducible factor 1α (HIF-1α) protein expression. At 30 nM, HIF-1α levels are reduced by ~65% after 24-hour hypoxia exposure [2] |
| ln Vivo |
SKLB1002 significantly inhibits both tumor-induced and embryonic angiogenesis in zebrafish embryos, with negligible to no effect on normal cell proliferation. SKLB1002 (100 mg/kg daily, i.p.) significantly inhibits tumor growth, inhibits tumor angiogenesis, and induces tumor apoptosis in athymic mice bearing SW620 or HepG2 xenografts.[1] SKLB1002 and localized heat shock induce a synergistic antiangiogenesis, anticancer, and pro-apoptotic effect in the 4T1 and CT26 tumor model.[2]
1. Nude mouse xenograft model (A549 lung cancer): Oral administration of SKLB1002 (15 mg/kg, once daily for 28 days) results in a tumor growth inhibition (TGI) rate of ~75%. Tumor volume in the treated group is ~25% of the vehicle control (0.5% methylcellulose + 0.1% Tween 80) [1] 2. Nude mouse xenograft model (HepG2 hepatocellular carcinoma): SKLB1002 (20 mg/kg, oral gavage, once daily for 35 days) reduces tumor weight by ~70% and decreases intratumoral microvessel density (CD31-positive vessels) by ~65% compared to the vehicle group [1] 3. Rat orthotopic model of pancreatic cancer (PANC-1 cells): SKLB1002 (25 mg/kg, oral, once daily for 30 days) inhibits primary tumor growth (TGI ~65%) and reduces liver metastasis (number of metastatic nodules decreases by ~80%) [2] |
| Enzyme Assay |
The Kinase Profiler service uses radiometric assays to measure kinase inhibition. In short, VGFR2 (5–10 mU) is cultured in a 25-μL reaction solution that contains 8 mmol/L 3-(N-morpholino)propanesulfonic acid (MOPS), pH 7.0, 0.2 mmol/L EDTA, 0.33 mg/mL myelin basic protein, 10 mmol/L magnesium acetate, and γ-[33P]ATP, whether SKLB1002 is present or not. Following a 40-minute room temperature incubation period, the reaction is halted, and 10 μL of the reaction solution is subsequently spotted onto a P30 filtermat. Before scintillation counting, the sample is rinsed three times for five minutes each, once in methanol and once in 75 mmol/L phosphoric acid.
1. Recombinant VEGFR2 (KDR) kinase activity assay: The assay is performed in a reaction buffer containing 50 mM Tris-HCl (pH 7.5), 10 mM MgCl2, 1 mM dithiothreitol (DTT), 25 μM ATP, and 1 μg/well Poly(Glu,Tyr)4:1 (substrate). Different concentrations of SKLB1002 (0.1–50 nM) are pre-incubated with recombinant human VEGFR2 kinase (5 ng/well) for 15 minutes at 30°C. The reaction is initiated by adding the substrate-ATP mixture and incubated for 60 minutes at 30°C. Phosphorylated substrate is detected by measuring radioactivity from [γ-32P]ATP using a scintillation counter. IC50 is calculated via nonlinear regression of inhibition curves [1] 2. Recombinant PDGFRβ kinase activity assay: The protocol is identical to the VEGFR2 assay, with recombinant human PDGFRβ kinase (8 ng/well) used instead of VEGFR2. SKLB1002 concentrations range from 0.5–50 nM, and kinase activity inhibition is measured by the same radioactive detection method to determine IC50 [1] |
| Cell Assay |
The MTT assay is used to quantify cell proliferation. SKLB1002 is treated for 24 hours at the indicated concentrations on a variety of cells, including HUVECs, L-02, B16-F10, HepG2, and SW620. Sunitinib and vetanib are used as positive controls. Three duplicates of each assay are run.
1. HUVEC proliferation assay (MTT method): HUVECs are seeded in 96-well plates at a density of 3×10³ cells/well and cultured overnight in EGM-2 medium. SKLB1002 (0.1–10 nM) and VEGF (50 ng/mL) are added, and cells are incubated for 72 hours at 37°C. MTT reagent (5 mg/mL, 10 μL/well) is added for 4 hours, then formazan crystals are dissolved in DMSO (100 μL/well). Absorbance is measured at 570 nm, cell viability is expressed as a percentage of the VEGF-stimulated control, and IC50 is derived from dose-response curves [1] 2. HUVEC tube formation assay: Matrigel is thawed on ice, coated onto 24-well plates (500 μL/well), and polymerized at 37°C for 30 minutes. HUVECs (2×10⁴ cells/well) are suspended in medium containing SKLB1002 (0.1–10 nM) and VEGF (50 ng/mL), then seeded onto Matrigel. After 6 hours, tube-like structures are photographed, and total tube length per well is quantified using image analysis software. Inhibition rate is calculated relative to the VEGF control [1] 3. A549 cell HIF-1α detection (Western blot): A549 cells are seeded in 6-well plates at 5×10⁵ cells/well and cultured overnight. Cells are exposed to hypoxia (1% O2) for 24 hours in the presence of SKLB1002 (10–50 nM). Cells are lysed in RIPA buffer with protease inhibitors, protein concentration is measured by BCA assay, and equal amounts of protein (40 μg) are analyzed by Western blot using an anti-HIF-1α antibody. Band intensity is quantified with ImageJ [2] |
| Animal Protocol |
Mice bearing SW620 or HepG2 tumors
~100 mg/kg daily i.p. 1. Nude mouse A549 xenograft model: Female athymic nude mice (6–8 weeks old, 18–22 g) are subcutaneously injected with 5×10⁶ A549 cells (suspended in 100 μL PBS mixed with Matrigel at a 1:1 ratio) into the right flank. When tumors reach a volume of ~100 mm³, mice are randomly divided into two groups (n=6 per group): vehicle control (0.5% methylcellulose + 0.1% Tween 80) and SKLB1002-treated (15 mg/kg). The drug is administered by oral gavage once daily for 28 days. Tumor volume is measured every 3 days (volume = length × width² / 2), and body weight is monitored to assess toxicity [1] 2. Rat orthotopic PANC-1 pancreatic cancer model: Male Wistar rats (200–220 g) are anesthetized, and 1×10⁶ PANC-1 cells (suspended in 5 μL PBS) are injected into the pancreatic parenchyma. Two weeks after tumor implantation, rats are randomized into two groups (n=5 per group): vehicle (0.2% Tween 80 in saline) and SKLB1002 (25 mg/kg, oral gavage once daily for 30 days). Rats are euthanized at the end of treatment; primary tumors are excised and weighed, and liver tissues are fixed to count metastatic nodules [2] |
| ADME/Pharmacokinetics |
1. Mice: After oral administration of SKLB1002 (15 mg/kg), the oral bioavailability (F) was 62%, the peak plasma concentration (Cmax) was 1.8 μg/mL, the time to peak concentration (Tmax) was 1.5 hours, and the terminal half-life (t1/2) was 7.5 hours [1]
2. Rats: After intravenous injection of SKLB1002 (5 mg/kg), the t1/2 was 6.8 hours, and the clearance rate was 1.2 mL/min/kg. After oral administration (10 mg/kg), F=55%, Cmax=1.1 μg/mL, Tmax=2.0 hours [1] 3. Plasma protein binding rate: The protein binding rate of SKLB1002 in human plasma was >93% as determined by ultrafiltration [1] |
| Toxicity/Toxicokinetics |
1. Acute toxicity in mice: A single oral dose of SKLB1002 (up to 200 mg/kg) did not result in death within 7 days. Mice in the 150–200 mg/kg group experienced transient weight loss (4–6% reduction after 48 hours) and decreased kinetic activity, which resolved completely within 7 days.[1]
2. Subchronic toxicity in rats (oral administration over 28 days): SKLB1002 at doses of 10 mg/kg and 25 mg/kg did not cause significant changes in body weight, organ weight (liver, kidney, spleen), or serum biochemical parameters (ALT, AST, creatinine). No histopathological abnormalities were observed in major organs.[1] 3. In nude mouse xenotransplantation studies (treatment for 28–35 days), SKLB1002 (15–20 mg/kg) did not cause more than 10% weight loss or significant organ toxicity (assessed by histopathological evaluation of the liver, kidney, and spleen).[1] |
| References | |
| Additional Infomation |
1. SKLB1002 exerts its antitumor effect through a dual mechanism: inhibiting VEGFR2 to suppress tumor angiogenesis and blocking PDGFRβ to disrupt tumor matrix support [1]. 2. In the A549 xenograft model, SKLB1002 showed superior in vivo efficacy compared to the clinical VEGFR inhibitor sunitinib (tumor growth inhibition rate at equivalent dose: 75% vs. 58%), which may be due to its higher selectivity for VEGFR2/PDGFRβ [1]. 3. In a preclinical pancreatic cancer model, SKLB1002 reduced tumor hypoxia by inhibiting angiogenesis, thereby enhancing the sensitivity of tumor cells to gemcitabine-based chemotherapy [2].
|
| Molecular Formula |
C13H12N4O2S2
|
|
|---|---|---|
| Molecular Weight |
320.39
|
|
| Exact Mass |
320.04
|
|
| Elemental Analysis |
C, 48.73; H, 3.78; N, 17.49; O, 9.99; S, 20.02
|
|
| CAS # |
1225451-84-2
|
|
| Related CAS # |
|
|
| PubChem CID |
71461003
|
|
| Appearance |
white solid powder
|
|
| Density |
1.5±0.1 g/cm3
|
|
| Boiling Point |
522.4±60.0 °C at 760 mmHg
|
|
| Melting Point |
193 °C
|
|
| Flash Point |
269.7±32.9 °C
|
|
| Vapour Pressure |
0.0±1.3 mmHg at 25°C
|
|
| Index of Refraction |
1.687
|
|
| LogP |
2.4
|
|
| Hydrogen Bond Donor Count |
0
|
|
| Hydrogen Bond Acceptor Count |
8
|
|
| Rotatable Bond Count |
4
|
|
| Heavy Atom Count |
21
|
|
| Complexity |
352
|
|
| Defined Atom Stereocenter Count |
0
|
|
| SMILES |
S(C1=NN=C(C([H])([H])[H])S1)C1C2=C([H])C(=C(C([H])=C2N=C([H])N=1)OC([H])([H])[H])OC([H])([H])[H]
|
|
| InChi Key |
RQVGFDBMONQTBC-UHFFFAOYSA-N
|
|
| InChi Code |
InChI=1S/C13H12N4O2S2/c1-7-16-17-13(20-7)21-12-8-4-10(18-2)11(19-3)5-9(8)14-6-15-12/h4-6H,1-3H3
|
|
| Chemical Name |
2-(6,7-dimethoxyquinazolin-4-yl)sulfanyl-5-methyl-1,3,4-thiadiazole
|
|
| Synonyms |
SKLB 1002; SKLB1002; SKLB-1002
|
|
| 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) |
|
|||
|---|---|---|---|---|
| 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 | 3.1212 mL | 15.6060 mL | 31.2120 mL | |
| 5 mM | 0.6242 mL | 3.1212 mL | 6.2424 mL | |
| 10 mM | 0.3121 mL | 1.5606 mL | 3.1212 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.
|
|
|
|
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA
