VEGFR2 (IC50 = 0.2 nM); VEGFR3 (IC50 = 0.7 nM); c-Kit (IC50 = 14.8 nM); c-Kit (IC50 = 14.8 nM); c-Kit (IC50 = 14.8 nM)

体外活性：安罗替尼（原名 AL3818）是一种新型有效的多激酶抑制剂，可抑制 VEGFR2/3、FGFR1-4、PDGFRα/β、c-Kit 和 Ret。安罗替尼作为受体酪氨酸激酶 (RTK) 抑制剂，具有潜在的抗肿瘤和抗血管生成活性。安罗替尼在体外显着减少 AN3CA 细胞数量，其特点是突变 FGFR2 蛋白的高表达。每日口服安罗替尼（5 mg/kg）使 55% 的接受治疗的动物出现完全缓解，并且在 29 次治疗后，AN3CA 肿瘤的肿瘤体积和肿瘤重量分别减少了 94% 和 96%。天治疗周期。尽管卡铂和紫杉醇未能改变肿瘤生长，但与单独使用安罗替尼治疗相比，与安罗替尼的组合似乎并未表现出更好的效果。激酶检测：安罗替尼（原名 AL3818）是一种新型有效的多激酶抑制剂，可抑制 VEGFR2/3、FGFR1-4、PDGFRα/β、c-Kit 和 Ret。细胞测定：AL3818 在体外显着减少 AN3CA 细胞数量，其特点是突变 FGFR2 蛋白的高表达。每日口服 AL3818 (5 mg/kg) 可使 55% 的接受治疗动物出现完全缓解，并且在 29 次治疗后，AN3CA 肿瘤的肿瘤体积减小，肿瘤重量分别减少 94% 和 96%。天治疗周期。尽管卡铂和紫杉醇未能改变肿瘤生长，但与单独使用 AL3818 治疗相比，与 AL3818 的组合似乎并未表现出更好的效果。

每日口服安罗替尼（5 mg/kg）使 55% 的接受治疗的动物出现完全缓解，并且在 29 次治疗后，AN3CA 肿瘤的肿瘤体积和肿瘤重量分别减少了 94% 和 96%。天治疗周期。尽管卡铂和紫杉醇未能改变肿瘤生长，但与单独使用安罗替尼治疗相比，与安罗替尼的组合似乎并未表现出更好的效果。

安罗替尼（原名 AL3818）是一种新型强效多激酶抑制剂，可阻断 Ret、FGFR1-4、PDGFRα/β、c-Kit 和 VEGFR2/3。

如前所述，使用ELISA测定安洛替尼对酪氨酸激酶的抑制活性。22 ATP与酪氨酸激酶的反应在反应缓冲液（50 mmol/L HEPES pH 7.4，50 mmol/L MgCl2，0.5 mmol/L MnCl2，0.2 mmol/L Na3VO4，1 mmol/L DTT）中启动，并在37°C下在预涂有20μg/mL Poly（Glu，Tyr）4:1的96孔板中孵育1小时。将平板与PY99抗体一起孵育，然后与HRP偶联的抗小鼠IgG一起孵育。与邻苯二胺溶液反应后，加入2N H2SO4终止反应，使用Synergy H4 Hybrid阅读器在490 nm处测量吸光度[3]。

在体外，AL3818 显着降低了 AN3CA 细胞的数量，这是通过突变 FGFR2 蛋白的高表达来识别的。经过 29 天的治疗周期后，每天口服 AL3818（5 mg/kg），55% 的治疗动物出现完全缓解，AN3CA 肿瘤的肿瘤体积和肿瘤重量分别减少了 94% 和 96%。分别。与单独使用 AL3818 治疗相比，卡铂和紫杉醇的组合似乎没有更大的效果，尽管它们无法改变肿瘤的生长。

human colon cancer SW620 xenograft model（Balb/cA-nude mice, 5-6 weeks old)
0.75, 1.5, 3 and 6 mg/kg
oral

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Female nude mice (Balb/cA‐nude, 5‐6 weeks old), purchased from Shanghai Laboratory Animal Center (Chinese Academy of Sciences, Shanghai, China), were housed in sterile cages under laminar airflow hoods in a specific pathogen‐free room with a 12‐hour light/12‐hour dark schedule, and fed autoclaved chow and water ad libitum. Human tumor xenografts were established by s.c. inoculating cells into the left axilla of nude mice. When tumor volumes reached 100‐200 mm3, mice were divided randomly into control and treatment groups. Control groups were given vehicle alone, and treatment groups received oral anlotinib or sunitinib daily. Tumor volume was calculated as (length × width2)/2. Tumor growth inhibition was calculated from the start of treatment by comparing changes in tumor volumes for control and treatment groups.[1]

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Rat studies[3]
Rats were randomly assigned to four groups (five male and five female rats per group) to receive a single oral dose of anlotinib at 1.5, 3, or 6 mg/kg (via gavage) or a single intravenous dose at 1.5 mg/kg (from the tail vein). Serial blood samples (around 0.25 mL; before and 5, 15, and 30 min and 1, 2, 4, 6, 8, 11, and 24 h after dosing) were collected in heparinized tubes from the orbital sinuses of rats under isoflurane anesthesia and centrifuged at 1300×g for 10 min to yield plasma fractions. Rats under isoflurane anesthesia were killed by bleeding from the abdominal aorta at 1, 4, 8, and 24 h (three male and three female rats per time point) after a single oral dose of anlotinib at 3 mg/kg. [3]

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Tumor-bearing mouse studies[3]
Female tumor-bearing mice were randomly assigned to three groups (20 mice per group) to receive a single oral dose of anlotinib at 0.75, 1.5, or 3 mg/kg (via gavage). Mice under isoflurane anesthesia were killed by bleeding from the orbital sinus at 2, 4, 8, and 24 h (five mice per time point) after dosing.

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Dog study[3]
Dogs were randomly assigned to four groups (three male and three female dogs per group) to receive a single oral dose of anlotinib at 0.5, 1, or 2 mg/kg (via gavage) or a single intravenous dose at 0.5 mg/kg (from left forelimb vein).

Plasma pharmacokinetics of anlotinib in rats and in dogs [3]
Mean plasma concentrations of anlotinib over time after a single dose of anlotinib in rats and dogs are shown in Figure 1; the plasma pharmacokinetic parameters of anlotinib are summarized in Table 1. After oral administration, levels of systemic exposure to anlotinib, i.e., plasma maximum concentration (Cmax) and area under the plasma concentration-time curve up to 24 h (AUC0-24 h), in female rats tended to be greater than those in male rats at the tested dose range 1.5–6 mg/kg, while gender differences in plasma Cmax and AUC0-24 h of anlotinib were not significant in dogs at the dose range 0.5–2 mg/kg. The plasma Cmax and AUC0-24h increased as the anlotinib dose increased in an over-proportional manner in rats and dogs (Table 2). Anlotinib was highly bound in rat, dog, and human plasma with unbound fractions in plasma (fu) of 2.9%, 4.0%, and 7.3%, respectively. These fu values were independent of total plasma concentration of anlotinib, suggesting that such total concentration of anlotinib is a good measure of the changes in its unbound concentration in plasma for the species. As shown in Table 3, anlotinib exhibited binding affinity for α1-acid glycoprotein similar to imatinib, another tyrosine kinase inhibitor. However, it exhibited substantially higher affinity for albumin than imatinib. Unlike imatinib with an nKα1-acid-glycoprotein/nKalbumin ratio of 92.0, such a ratio for anlotinib was 0.9 (<7.7), suggesting the high excess of plasma concentration of albumin (600 μmol/L) over α1-acid glycoprotein (20 μmol/L) could not be compensated for circulating anlotinib in humans. It is worth mentioning that anlotinib exhibited notably higher affinity for plasma lipoproteins, particularly for low density lipoproteins and very low density lipoproteins, than for albumin and α1-acid glycoprotein. After oral administration, anlotinib was rapidly absorbed from the gastrointestinal tract in rats and dogs (Figure 1). Dogs tended to exhibit greater oral bioavailability (F) of anlotinib than rats. Terminal half-lives (t1/2) of anlotinib in rats and dogs after intravenous administration were comparable with the respective t1/2 values after oral administration. Dogs exhibited a longer mean t1/2 of anlotinib than rats. This t1/2 difference appeared to be attributed mainly to interspecies difference in total plasma clearance (CLtot,p). Anlotinib's mean apparent volume of distribution at steady state (VSS) in rats was 40 times as much as the rat volume of total body water and the value of VSS in dogs was 12 times as much as the dog volume of total body water15, suggesting the compound was distributed widely into various body fluids and tissues. In rats that received an intravenous dose of anlonitib, only small amounts of the unchanged compound were excreted into urine, bile, and feces (Table 1), suggesting that metabolism was the major elimination route of anlotinib.

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Intestinal absorption-related properties of anlotinib [3]
Intestinal absorption of a drug is a combined result of its solubility in gastrointestinal fluids, membrane permeability, and substrate specificity to efflux system of the intestinal epithelia. Anlotinib exhibited pH-dependent aqueous solubility, ie, >1 g/mL at pH 1.7 (the stomach), 114 μg/mL at pH 4.6 (the duodenum), and 0.89 μg/mL at pH 6.5 (the jejunum and the ileum). The solubility values of anlotinib at pH 1.7 and 4.6 were greater than the compound's minimum solubility necessary to achieve adequate intestinal absorption at the dose 6 mg/kg, but the solubility value at pH 6.5 was lower than the minimum solubility. The minimum solubility was deduced according to a bar chart, by Lipinski, that depicts the minimum solubility for compounds with low, medium, and high permeability at doses of 0.1, 1, and 10 mg/kg16. Anlotinib exhibited good membrane permeability across Caco-2 cell monolayers, expressing MDR1, MRP2, and BCRP, with a mean apparent permeability coefficient (Papp) of 3.5×10−6 cm/s. The compound exhibited a mean efflux ratio (EfR) of 0.91±0.22, suggesting that its transport across the cell monolayer did not affected by the apical efflux transporters in Caco-2 cells (Supplementary Figure S1). Physicochemical properties of anlotinib (predicted using ACD/Percepta; Toronto, Ontario, Canada), ie, molecular mass (407 Da; favorable value, <500 Da), hydrogen-bonding capacity (HBA+HBD, 6+3; <12), topological polar surface area (TPSA, 82.4 Å2; <140 Å2), and molecular flexibility (NROTB, 6; <10), supported its good membrane permeability. Measured LogD values were −0.89 at pH 1.7, 2.10 at pH 4.6, and 2.38 at pH 6.5 (favorable range, 0–5).

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Tissue distribution of anlotinib in rats and tumor-bearing mice [3]
Levels of various tissue exposures to anlotinib (measured using associated tissue homogenate samples) in rats and tumor-bearing mice after an oral dose of the compound were significantly higher than the associated systemic exposure level (Figure 2). In rats, the lung exhibited the highest exposure level, which was 197 times as high as the systemic exposure level. Meanwhile, the rat liver, kidneys, and heart also exhibited high exposure levels, which were 49, 54, and 32 times as much as the systemic exposure level. Anlotinib penetrated the rat brain, with a brain homogenate AUC0-24h level comparable to the associated plasma level. In tumor-bearing mice, the level of tumor tissue exposure to the compound increased as the dose increased; it was 13 times as high as the systemic exposure level.

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Metabolism of anlotinib [3]
Because neither hepatobiliary nor renal excretion of unchanged compound was the main elimination route, metabolites of anlotinib in rat and dog samples were detected and characterized. As a result, a total of 12 anlotinib metabolites (M1–M12) were detected in the plasma, bile, urine, and feces samples of rats after dosing (Table 4). Eight of the metabolites, ie, M2, M4, M5, M6, M8, M9, M10, and M11, were found in plasma. All these metabolites occurred in rat bile and urine samples, except for M7 and M11, which occurred only in rat bile samples. In dogs, a total of 5 metabolites of anlotinib were detected in plasma samples; they were M4, M8, M9, M10, and M11. After liquid chromatography/mass spectrometry-based characterization of these metabolites, metabolic pathways of anlotinib were proposed (Figure 3). The major metabolic pathways of anlotinib in rats were probably the hydroxylation to form M10 and M11 and the dealkylation to form M8. The metabolites M10 and M11 were two major plasma metabolites of anlotinib in rats, while M8 was further glucuronized to form M6, a major plasma and biliary metabolite of anlotinib. To further characterize these metabolic pathways, in vitro metabolism studies were performed for anlotinib. As a result, multiple human cytochrome P450 enzymes, ie, CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4, and CYP3A5, were found to be able to mediate the oxidation of anlotinib to form M10, M11, and M8 (Figure 4A). Among these enzymes were CYP3A4 and CYP3A5 that exhibited the greatest metabolic capabilities. As shown in Figure 4B, the metabolites M10, M11, and M8 were also detected in samples of anlotinib after being incubated with NADPH-fortified rat liver microsomes, dog liver microsomes, and human liver microsomes under the same conditions. The total amounts of metabolites formed were different for the tested liver microsomes of different species, suggesting the highest oxidation rate by rat liver microsomes followed by dog liver microsomes, and then by human liver microsomes.

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In vitro inhibitory activity of anlotinib on drug metabolism enzymes and transporters [3]
As shown in Table 5, anlotinib exhibited, in vitro, significant potency to inhibit CYP3A4 and CYP2C9 with IC50 values of <1 μmol/L; such inhibitory potency towards CYP2C19, CYP2C8, UGT1A1, UGT1A4, UGT1A9, and UGT2B15 was moderate, with IC50 values of 1–10 μmol/L. This tyrosine kinase inhibitor exhibited low inhibitory potency in vitro towards human CYP2B6, CYP2D6, UGT1A6, UGT2B7, OATP1B1, OAT3, OCT2, MDR1, and BCRP with values of IC50 greater than 10 μmol/L. No significant inhibitory potency of anlotinib was found towards human CYP1A2, CYP3A5, OATP1B3, OAT1, and MRP1. Anlotinib was not an in vitro substrate of OATP1B1, OATP1B3, OAT1, OAT3, OCT2, MDR1, and BCRP (Supplementary Table S1).

On the 4/0 schedule, no DLT was observed in the first four patients at the starting dose of 5 mg/day. However, at 10 mg/day, one patient developed grade 3 hypertension among the first three patients treated. An additional patient was enrolled and also developed grade 3 hypertension. Therefore, the further dose escalation was halted. Meanwhile, PK study revealed a continuously significant anlotinib accumulation in patients who received continuous administration (data not shown). Based on the PK profile of anlotinib and the two DLTs observed at the dose of 10 mg/day, we modified the administration protocol from the 4/0 schedule to the 2/1.[2]
On the 2/1 schedule, because none of the three patients experienced DLT at initial doses of 10 mg/day, the dose escalation proceeded to 16 mg/day. Two of the three patients in the 16 mg cohort experienced DLT (one grade 3 fatigue and one grade 3 hypertension). Therefore, the MTD had been exceeded, and the next lower dose of 12 mg/day was further evaluated by entering additional patients. None of the initial three patients experienced grade 3/4 adverse events. On the basis, 12 mg once daily was selected for the expanding study. [2]
A total of 21 patients received the 12 mg/day dose on the 2/1 schedule. During the first 2 cycles, all the patients experienced an adverse event of any causality. All the hematologic toxicities were mild. As illustrated in Table 2, the most common non-hematologic adverse events were hypothyroidism, triglyceride elevation, total cholesterol elevation, ALT elevation, diarrhea, and proteinuria. During the first 2 cycles, a total of two patients (10 %) experienced grade 3 adverse events (one triglyceride elevation and one lipase elevation). During all treatment cycles, there were six patients (29 %) with grade 3/4 adverse events. The most common (>5 %) non-hematologic grade 3 adverse events were hypertension, triglyceride elevation, hand-foot skin reaction, and lipase elevation.

[1]. Cancer Sci . 2018 Apr;109(4):1207-1219.

[2]. J Hematol Oncol . 2016 Oct 4;9(1):105.

[3]. Acta Pharmacol Sin . 2018 Jun;39(6):1048-1063.

Anlotinib has been investigated for the treatment of Non-small Cell Lung Cancer and Metastatic Colorectal Cancer.
Catequentinib is a receptor tyrosine kinase (RTK) inhibitor with potential antineoplastic and anti-angiogenic activities. Upon administration, catequentinib targets multiple RTKs, including vascular endothelial growth factor receptor type 2 (VEGFR2) and type 3 (VEGFR3). This agent may both inhibit angiogenesis and halt tumor cell growth.

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Drug Indication
Treatment of Ewing sarcoma, Treatment of soft tissue sarcomas

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Catequentinib Hydrochloride is the hydrochloride salt form of catequentinib, a receptor tyrosine kinase (RTK) inhibitor with potential antineoplastic and anti-angiogenic activities. Upon administration, catequentinib targets multiple RTKs, including vascular endothelial growth factor receptor type 2 (VEGFR2) and type 3 (VEGFR3). This agent may both inhibit angiogenesis and halt tumor cell growth.

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brogating tumor angiogenesis by inhibiting vascular endothelial growth factor receptor-2 (VEGFR2) has been established as a therapeutic strategy for treating cancer. However, because of their low selectivity, most small molecule inhibitors of VEGFR2 tyrosine kinase show unexpected adverse effects and limited anticancer efficacy. In the present study, we detailed the pharmacological properties of anlotinib, a highly potent and selective VEGFR2 inhibitor, in preclinical models. Anlotinib occupied the ATP-binding pocket of VEGFR2 tyrosine kinase and showed high selectivity and inhibitory potency (IC50 <1 nmol/L) for VEGFR2 relative to other tyrosine kinases. Concordant with this activity, anlotinib inhibited VEGF-induced signaling and cell proliferation in HUVEC with picomolar IC50 values. However, micromolar concentrations of anlotinib were required to inhibit tumor cell proliferation directly in vitro. Anlotinib significantly inhibited HUVEC migration and tube formation; it also inhibited microvessel growth from explants of rat aorta in vitro and decreased vascular density in tumor tissue in vivo. Compared with the well-known tyrosine kinase inhibitor sunitinib, once-daily oral dose of anlotinib showed broader and stronger in vivo antitumor efficacy and, in some models, caused tumor regression in nude mice. Collectively, these results indicate that anlotinib is a well-tolerated, orally active VEGFR2 inhibitor that targets angiogenesis in tumor growth, and support ongoing clinical evaluation of anlotinib for a variety of malignancies.[1]

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Background: Anlotinib is a novel multi-target tyrosine kinase inhibitor that is designed to primarily inhibit VEGFR2/3, FGFR1-4, PDGFR α/β, c-Kit, and Ret. We aimed to evaluate the safety, pharmacokinetics, and antitumor activity of anlotinib in patients with advanced refractory solid tumors. Methods: Anlotinib (5-16 mg) was orally administered in patients with solid tumor once a day on two schedules: (1) four consecutive weeks (4/0) or (2) 2-week on/1-week off (2/1). Pharmacokinetic sampling was performed in all patients. Twenty-one patients were further enrolled in an expanded cohort study on the recommended dose and schedule. Preliminary tumor response was also assessed. Results: On the 4/0 schedule, dose-limiting toxicity (DLT) was grade 3 hypertension at 10 mg. On the 2/1 schedule, DLT was grade 3 hypertension and grade 3 fatigue at 16 mg. Pharmacokinetic assessment indicated that anlotinib had long elimination half-lives and significant accumulation during multiple oral doses. The 2/1 schedule was selected, with 12 mg once daily as the maximum tolerated dose for the expanding study. Twenty of the 21 patients (with colon adenocarcinoma, non-small cell lung cancer, renal clear cell cancer, medullary thyroid carcinoma, and soft tissue sarcoma) were assessable for antitumor activity of anlotinib: 3 patients had partial response, 14 patients had stable disease including 12 tumor burden shrinkage, and 3 had disease progression. The main serious adverse effects were hypertension, triglyceride elevation, hand-foot skin reaction, and lipase elevation. Conclusions: At the dose of 12 mg once daily at the 2/1 schedule, anlotinib displayed manageable toxicity, long circulation, and broad-spectrum antitumor potential, justifying the conduct of further studies.[2]

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Anlotinib is a new oral tyrosine kinase inhibitor; this study was designed to characterize its pharmacokinetics and disposition. Anlotinib was evaluated in rats, tumor-bearing mice, and dogs and also assessed in vitro to characterize its pharmacokinetics and disposition and drug interaction potential. Samples were analyzed by liquid chromatography/mass spectrometry. Anlotinib, having good membrane permeability, was rapidly absorbed with oral bioavailability of 28%-58% in rats and 41%-77% in dogs. Terminal half-life of anlotinib in dogs (22.8±11.0 h) was longer than that in rats (5.1±1.6 h). This difference appeared to be mainly associated with an interspecies difference in total plasma clearance (rats, 5.35±1.31 L·h-1·kg-1; dogs, 0.40±0.06 L·h-1/kg-1). Cytochrome P450-mediated metabolism was probably the major elimination pathway. Human CYP3A had the greatest metabolic capability with other human P450s playing minor roles. Anlotinib exhibited large apparent volumes of distribution in rats (27.6±3.1 L/kg) and dogs (6.6±2.5 L/kg) and was highly bound in rat (97%), dog (96%), and human plasma (93%). In human plasma, anlotinib was predominantly bound to albumin and lipoproteins, rather than to α1-acid glycoprotein or γ-globulins. Concentrations of anlotinib in various tissue homogenates of rat and in those of tumor-bearing mouse were significantly higher than the associated plasma concentrations. Anlotinib exhibited limited in vitro potency to inhibit many human P450s, UDP-glucuronosyltransferases, and transporters, except for CYP3A4 and CYP2C9 (in vitro half maximum inhibitory concentrations, <1 μmol/L). Based on early reported human pharmacokinetics, drug interaction indices were 0.16 for CYP3A4 and 0.02 for CYP2C9, suggesting that anlotinib had a low propensity to precipitate drug interactions on these enzymes. Anlotinib exhibits many pharmacokinetic characteristics similar to other tyrosine kinase inhibitors, except for terminal half-life, interactions with drug metabolizing enzymes and transporters, and plasma protein binding.[3]

C23H22FN3O3

407.45

407.16

C, 67.80; H, 5.44; F, 4.66; N, 10.31; O, 11.78

1058156-90-3

1058156-90-3;1360460-82-7 (HCl);

25017411

Solid powder

3.7

82.4Ų

2

6

6

30

606

0

CC1=CC2=C(N1)C=CC(=C2F)OC3=C4C=C(C(=CC4=NC=C3)OCC5(CC5)N)OC

KSMZEXLVHXZPEF-UHFFFAOYSA-N

InChI=1S/C23H22FN3O3/c1-13-9-15-16(27-13)3-4-19(22(15)24)30-18-5-8-26-17-11-21(20(28-2)10-14(17)18)29-12-23(25)6-7-23/h3-5,8-11,27H,6-7,12,25H2,1-2H3

1-[[4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxyquinolin-7-yl]oxymethyl]cyclopropan-1-amine

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

注意: 如下所列的是一些常用的体内动物实验溶解配方，主要用于溶解难溶或不溶于水的产品（水溶度<1 mg/mL）。 建议您先取少量样品进行尝试，如该配方可行，再根据实验需求增加样品量。

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注射用配方1: DMSO : Tween 80： Saline = 10 : 5 : 85 (如： 100 μL DMSO → 50 μL Tween 80 → 850 μL Saline)
*生理盐水/Saline的制备：将0.9g氯化钠/NaCl溶解在100 mL ddH ₂ O中，得到澄清溶液。
注射用配方 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL DMSO → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)
注射用配方 3: DMSO : Corn oil = 10 : 90 (如： 100 μL DMSO → 900 μL Corn oil)
示例: 以注射用配方 3 (DMSO : Corn oil = 10 : 90) 为例说明, 如果要配制 1 mL 2.5 mg/mL的工作液, 您可以取 100 μL 25 mg/mL 澄清的 DMSO 储备液，加到 900 μL Corn oil/玉米油中, 混合均匀。

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注射用配方 4: DMSO : 20% SBE-β-CD in Saline = 10 : 90 [如：100 μL DMSO → 900 μL (20% SBE-β-CD in Saline)]
*20% SBE-β-CD in Saline的制备（4°C，储存1周）：将2g SBE-β-CD (磺丁基-β-环糊精) 溶解于10mL生理盐水中，得到澄清溶液。
注射用配方 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (如： 500 μL 2-Hydroxypropyl-β-cyclodextrin (羟丙基环胡精)→ 500 μL Saline)
注射用配方 6: DMSO : PEG300 : Castor oil : Saline = 5 : 10 : 20 : 65 (如： 50 μL DMSO → 100 μL PEG300 → 200 μL Castor oil → 650 μL Saline)
注射用配方 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (如： 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
注射用配方 8: 溶解于Cremophor/Ethanol (50 : 50), 然后用生理盐水稀释。
注射用配方 9: EtOH : Corn oil = 10 : 90 (如： 100 μL EtOH → 900 μL Corn oil)
注射用配方 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL EtOH → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)

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口服配方 1: 悬浮于0.5% CMC Na (羧甲基纤维素钠)
口服配方 2: 悬浮于0.5% Carboxymethyl cellulose (羧甲基纤维素)
示例: 以口服配方 1 (悬浮于 0.5% CMC Na)为例说明, 如果要配制 100 mL 2.5 mg/mL 的工作液, 您可以先取0.5g CMC Na并将其溶解于100mL ddH2O中，得到0.5%CMC-Na澄清溶液；然后将250 mg待测化合物加到100 mL前述 0.5%CMC Na溶液中，得到悬浮液。

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口服配方 3: 溶解于 PEG400 (聚乙二醇400)
口服配方 4: 悬浮于0.2% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 5: 溶解于0.25% Tween 80 and 0.5% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 6: 做成粉末与食物混合

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注意: 以上为较为常见方法，仅供参考， InvivoChem并未独立验证这些配方的准确性。具体溶剂的选择首先应参照文献已报道溶解方法、配方或剂型，对于某些尚未有文献报道溶解方法的化合物，需通过前期实验来确定（建议先取少量样品进行尝试），包括产品的溶解情况、梯度设置、动物的耐受性等。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。