| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
Apatinib HCl (Rivoceranib; YN-968D1), thehydrochloride salt of apatinib, is a potent, orally bioavailable, and selective EGFR inhibitor antiangiogenic and antineoplastic activities. Apatinib potently suppressed the kinase activities of VEGFR-2, c-kit and c-src, and inhibited cellular phosphorylation of VEGFR-2, c-kit and PDGFRβ. Apatinib effectively inhibited proliferation, migration and tube formation of human umbilical vein endothelial cells induced by FBS, and blocked the budding of rat aortic ring. In vivo, Apatinib alone and in combination with chemotherapeutic agents effectively inhibited the growth of several established human tumor xenograft models with little toxicity. A phase I study of Apatinib has shown encouraging antitumor activity and a manageable toxicity profile. These findings suggest that Apatinib has promise as an antitumor drug and might have clinical benefits.
| Targets |
VEGFR2 (IC50 = 1 nM); RET (IC50 = 13 nM)
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|---|---|
| ln Vitro |
Apatinib (YN968D1) exhibited a potent kinase suppression effect on VEGFR-2, c-kit, and c-src, as well as an inhibition of cellular phosphorylation of VEGFR-2, c-kit, and PDGFRβ. With an IC50 of 0.013 μM, 0.429 μM, and 0.53 μM, respectively, YN968D1 suppresses the activities of Ret, c-kit, and c-src. At concentrations up to 10 μM, YN968D1 did not significantly affect EGFR, Her-2, or FGFR1. In addition to blocking the budding of rat aortic ring, YN968D1 efficiently suppressed the proliferation, migration, and tube formation of human umbilical vein endothelial cells stimulated by FBS[1].
|
| ln Vivo |
YN968D1 both by itself and in conjunction with chemotherapeutic agents efficiently and minimally harmed the growth of multiple well-established human tumor xenograft models in vivo[1].
Apatinib was valid in tumor growth inhibition in vivo. The tumor volume decreased when compared with the control group (Figures 7a and b). In accordance with in vitro experiment, Figure 7c shows that Apatinib treatment increased the level of LC3-II and Bax, whereas the level of BCL-2 and VEGFR2 decreased in vivo. Immunohistochemistry showed that Apatinib decreased the expression of VEGFR2, p-STAT3 and BCL-2 in tumors formed by KHOS cells (Figure 7d). All the results revealed that Apatinib inhibited the growth of osteosarcoma in vivo [2]. |
| Enzyme Assay |
Enzyme‐linked immunosorbent assay. [1]
The inhibitory activity of YN968D1 against tyrosine kinases was determined using ELISA methodology described previously. VEGFR‐2 and PDGFR were purchased commercially; Her‐2, c‐kit and c‐src were activated intracellular protein tyrosine kinases expressed by Bab‐to‐Bac Baculovirus Expression Vector System and purified by Ni‐NTA spin columns. The optical density was measured at 490 nm using VERSAmax. The inhibitory activity was expressed as IC50, which was calculated from three independent experiments by the Logit method.[1]
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| Cell Assay |
The CCK8 assay was used to evaluate the cell viability as described previously.40 The day before the experiment, the cells were seeded 5000 cells per well in 96-well plates. The cells were incubated with Apatinib at an indicated condition.[2]
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| Animal Protocol |
Nude mouse human tumor xenograft model. The effects of Apatinib (YN968D1) on tumor growth were tested against various human tumors grown subcutaneously in BALB/cA nude mice. Tumor growth was initiated by subcutaneous inoculation of cells into mice. Tumors were allowed to establish and grow to 100–300 mm3, at which time the mice were randomized into experimental groups. YN968D1 was administered once daily by oral gavage for the indicated periods (Table 1). In combination treatment experiments, mice were administered YN968D1 alone by oral gavage; 5‐FU, oxaliplatin, docetaxel and doxorubicin alone by intravenous injection; or YN968D1 in combination with each cytotoxic drug at the indicated dose and schedule (Table 2). Tumor volume and bodyweight were monitored every other day or every 3 days, with the means indicated for groups of six (treated) or 12 (vehicle control) animals. Tumor volumes were determined by measuring the largest diameter (a) and its perpendicular (b) according to the formula (a × b2)/2. The evaluation index for inhibition was the relative tumor growth ratio according to the equation: T/C (%) = mean increase of tumor volumes of treated groups/mean increase of tumor volumes of control groups × 100%.[1]
A 4- to 6-week-old BALB/c nude mice were subcutaneously injected in the right flank with 2 × 106 KHOS cells. The mice were fed in specific pathogen-free conditions, and when a palpable mass developed, the mice were randomly divided into two sets and were administered DMSO or Apatinib 50 mg/kg orally daily for 30 days. The tumor was scaled every other day for 4 days. The tumor volume was counted by (length × width2/2). The mice were killed on the 13th day after the treatment. Tumor samples were prepared for western blot and IHC.[2] |
| References |
[1]. YN968D1 is a novel and selective inhibitor of vascular endothelial growth factor receptor-2 tyrosine kinase with potent activity in vitro and in vivo. Cancer Sci. 2011 Jul;102(7):1374-80.
[2]. Apatinib promotes autophagy and apoptosis through VEGFR2/STAT3/BCL-2 signaling in osteosarcoma. Cell Death Dis. 2017 Aug; 8(8): e3015. |
| Molecular Formula |
C24H24CLN5OMOLECULARWEIGHT
|
|---|---|
| Molecular Weight |
623.78300
|
| Exact Mass |
623.368
|
| Elemental Analysis |
C, 66.43; H, 5.57; Cl, 8.17; N, 16.14; O, 3.69
|
| CAS # |
1218779-89-5
|
| Related CAS # |
1218779-89-5 (HCl);1218779-75-9 (mesylate);811803-05-1;
|
| PubChem CID |
45136888
|
| Appearance |
Typically exists as solid at room temperature
|
| LogP |
3.832
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
6
|
| Heavy Atom Count |
31
|
| Complexity |
608
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
CCC(CCCCC[C@H]1C(=O)N[C@@H](CC2=CN(OC)C3=CC=CC=C23)C(=O)NC(C(CC)C)C(=O)N2CCCC[C@]2([H])C(=O)N1)=O
|
| InChi Key |
YJFMYZMORFXPKW-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C24H23N5O.ClH/c25-17-24(11-1-2-12-24)19-5-7-20(8-6-19)29-23(30)21-4-3-13-27-22(21)28-16-18-9-14-26-15-10-18/h3-10,13-15H,1-2,11-12,16H2,(H,27,28)(H,29,30)1H
|
| Chemical Name |
N-(4-(1-Cyanocyclopentyl)phenyl)-2-((pyridin-4-ylmethyl)amino)nicotinamide hydrochloride
|
| Synonyms |
1218779-89-5; YN968D1 Hydrochloride; N-[4-(1-cyanocyclopentyl)phenyl]-2-(pyridin-4-ylmethylamino)pyridine-3-carboxamide;hydrochloride; N-[4-(1-Cyanocyclopentyl)phenyl]-2-{[(pyridin-4-yl)methyl]amino}pyridine-3-carboxamide hydrogen chloride (1:1); N-(4-(1-Cyanocyclopentyl)phenyl)-2-((pyridin-4-ylmethyl)amino)nicotinamide hydrochloride; DTXSID70659600
|
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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 | 1.6031 mL | 8.0156 mL | 16.0313 mL | |
| 5 mM | 0.3206 mL | 1.6031 mL | 3.2063 mL | |
| 10 mM | 0.1603 mL | 0.8016 mL | 1.6031 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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